Immunology: A Multi-Disciplinary Program

The Department of Pediatrics has launched a program in immunology that includes additional curriculum incorporated into Departmental lecture series and Grand Rounds.  In addition, the program includes an expanding network of research opportunities from principal investigators interested in hosting a pediatric resident or fellow in their lab. This program is multidisciplinary, and includes research in Hematology, Transplantation, Neonatology, Asthma, Oncology, Infectious Disease, Critical Care and Rheumatology within the Department of Pediatrics. In addition the program spans across multiple departments and institutes at the Columbia University Medical Center, and involves collaboration with partners in Medicine, Microbiology and Immunology, Environmental Health, Systems Biology, and Cancer Genetics.

Primary Faculty

Research faculty and programs with the Department of Pediatrics include the following:

Thomas G. Diacovo, MD

Academic Title(s):

Director, Neonatal and Critical Care Research
Associate Professor of Pediatrics and Pathology and Cell Biology

Division(s):

Neonatology

Contact Information:

Tel: (212) 851-4683
Fax: (212) 851-4504
Email: td2142@columbia.edu

Research

The research activities of Dr. Diacovo's lab are multifold. The recruitment of white blood cells (WBC) into inflamed tissues is dependent upon a series of sequential adhesive interactions that occur between these cells and the microvasculature. Critical to this process is the activation of the class I phosphoinositide 3-kinases (PI3K) signaling pathway, which contributes to the directed migration of these cells into areas of inflammation. Dr. Diacovo's lab made the seminal observation that PI3K expressed in vascular endothelium are as essential for the ability of this cell type to form adhesive interactions with circulating WBC.
Using various molecular, biochemical, and intravital microscopic approaches, Dr. Diacovo is now determining how this signaling pathway regulates the proinflammatory state of vascular endothelium, and whether pharmacological inhibition may be of benefit in treating inflammatory conditions in humans. Work is currently focused on the role of class I PI3K in supporting neutrophil, monocyte, and T cell function and migration into tissues, and the role they play in tissue injury in animal models that mimic multiple sclerosis or atherosclerosis. Results of these studies should prove useful in guiding the development of pharmacological agents designed to block the activity of specific PI3K isoforms. Work for these studies are supported by the NIH grant HL075805.
Studies are also focus on the interplay between PI3K and PTEN, a phosphatase that regulates the activity of PI3K. Importantly, loss of PTEN activity has been associated with development of solid tumors (ie. breast cancer) and hematological malignancies (ie. adult T cell leukemia/lymphoma (ATLL)). In fact, mice deficient in PTEN activity in T cells (Cre/lox system) are known to develop a proliferative disease that is reminiscent of T cell lymphomas. The Diacovo lab has found that tumor development in these PTEN knockout mice can be significantly curtailed in the absence of specific PI3K isoforms. In collaboration with Dr. Adolfo Ferrando, an expert in T cell leukemia at the Irving Cancer Center at Columbia University, they will determine whether pharmacological inhibition of PI3Ks can rescue mice with T cell leukemia/lymphomas that result from alterations in PTEN activity. Funding for these studies are proved by the Leukemia and Lymphoma Society and the DOD grant PR093714.

Selected Publications

  • Randis TM, Diacovo, NA, Calafat J, Diacovo TG. Shedding light on class I PI3K activity in endothelium. Blood 2008; 111; 4827-4828.
  • Randis TM, Puri KD, Zhou H, Diacovo TG. Role of PI3Kd and PI3Kg in inflammatory arthritis and tissue localization of neutrophils I PI3K activity in endothelium. Eur J Immunol. 2008; 38:1215-1224.
  • Tassi I, Cella, M, Gilfillan, S, Turnbull I, Diacovo TG, Penninger JM, Colonna M. p110g and p110d PI-3Ksignaling pathways synergize to control development and effector functions of murine NK cells. Immunity 2007. 27:214-227.
  • Swat W, Montgrain V, Doggett TA, Douangpanya J, Puri K, Vermi W, Diacovo TG. The Essential Role of PI3Kd and PI3Kg in Thymocyte Survival. Blood. 2006, 107; 2415-2422.
  • Puri KD, Doggett TA, Huang C-Y, Douangpanya J, Hayflick J, Turner M, Penninger J, Diacovo TG. The role of endothelial PI3Kg activity in neutrophil trafficking. Blood. 2005, 106; 150-157.

Click here to view Dr. Diacovo's profile.

Adolfo Ferrando, MD, PhD

Academic Title(s):

Associate Professor of Pediatrics and Pathology
Director WOLF Foundation Leukemia/Lymphoma Laboratory

Division(s):

Pediatric Oncology

Contact Information:

Tel: (212) 851-4611
Fax: (212) 851-5256
Email: af2196@columbia.edu

Research

Dr. Ferrnado's laboratory is studying the developmental characterization of intratymic T-cell development and it relevance in the pathogenesis of T-cell lymphoblastic leukemia

Selected Publications

  • The role of NOTCH1 signaling in T-ALL.Ferrando AA. Hematology Am Soc Hematol Educ Program. 2009:353-61.
  • T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993). Marks DI, Paietta EM, Moorman AV, Richards SM, Buck G, DeWald G, Ferrando A, Fielding AK, Goldstone AH, Ketterling RP, Litzow MR, Luger SM, McMillan AK, Mansour MR, Rowe JM, Tallman MS, Lazarus HM. Blood. 2009 Dec 10;114(25):5136-45.
  • Therapeutic targeting of NOTCH1 signaling in T-cell acute lymphoblastic leukemia. Palomero T, Ferrando A.Clin Lymphoma Myeloma. 2009;9 Suppl 3:S205-10. Review.
  • Prognostic implications of NOTCH1 and FBXW7 mutations in adults with T-cell acute lymphoblastic leukemia treated on the MRC UKALLXII/ECOG E2993 protocol. Mansour MR, Sulis ML, Duke V, Foroni L, Jenkinson S, Koo K, Allen CG, Gale RE, Buck G, Richards S, Paietta E, Rowe JM, Tallman MS, Goldstone AH, Ferrando AA, Linch DC. J Clin Oncol. 2009 Sep 10;27(26):4352-6.
  • WT1 mutations in T-ALL. Tosello V, Mansour MR, Barnes K, Paganin M, Sulis ML, Jenkinson S, Allen CG, Gale RE, Linch DC, Palomero T, Real P, Murty V, Yao X, Richards SM, Goldstone A, Rowe J, Basso G, Wiernik PH, Paietta E, Pieters R, Horstmann M, Meijerink JP, Ferrando AA. Blood. 2009 Jul 30;114(5):1038-45.
  • CSL-MAML-dependent Notch1 signaling controls T lineage-specific IL-7R{alpha} gene expression in early human thymopoiesis and leukemia. González-García S, García-Peydró M, Martín-Gayo E, Ballestar E, Esteller M, Bornstein R, de la Pompa JL, Ferrando AA, Toribio ML. J Exp Med. 2009 Apr 13;206(4):779-91. Erratum in: J Exp Med. 2009 Jul 6;206(7):1633.
  • ChIP-on-chip significance analysis reveals large-scale binding and regulation by human transcription factor oncogenes. Margolin AA, Palomero T, Sumazin P, Califano A, Ferrando AA, Stolovitzky G. Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):244-9.
  • Gamma-secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemia. Real PJ, Tosello V, Palomero T, Castillo M, Hernando E, de Stanchina E, Sulis ML, Barnes K, Sawai C, Homminga I, Meijerink J, Aifantis I, Basso G, Cordon-Cardo C, Ai W, Ferrando A. Nat Med. 2009 Jan;15(1):50-8.
  • Oncogenic NOTCH1 control of MYC and PI3K: challenges and opportunities for anti-NOTCH1 therapy in T-cell acute lymphoblastic leukemias and lymphomas. Palomero T, Ferrando A. Clin Cancer Res. 2008 Sep 1;14(17):5314-7.
  • The role of the PTEN/AKT Pathway in NOTCH1-induced leukemia. Palomero T, Dominguez M, Ferrando AA. Cell Cycle. 2008 Apr 15;7(8):965-70.
  • NOTCH1 extracellular juxtamembrane expansion mutations in T-ALL. Sulis ML, Williams O, Palomero T, Tosello V, Pallikuppam S, Real PJ, Barnes K, Zuurbier L, Meijerink JP, Ferrando AA. Blood. 2008 Aug 1;112(3):733-40.
  • Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia. Palomero T, Sulis ML, Cortina M, Real PJ, Barnes K, Ciofani M, Caparros E, Buteau J, Brown K, Perkins SL, Bhagat G, Agarwal AM, Basso G, Castillo M, Nagase S, Cordon-Cardo C, Parsons R, Zúñiga-Pflücker JC, Dominguez M, Ferrando AA. Nat Med. 2007 Oct;13(10):1203-10.
  • The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia. Thompson BJ, Buonamici S, Sulis ML, Palomero T, Vilimas T, Basso G, Ferrando A, Aifantis I. J Exp Med. 2007 Aug 6;204(8):1825-35.
  • Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. Saal LH, Johansson P, Holm K, Gruvberger-Saal SK, She QB, Maurer M, Koujak S, Ferrando AA, Malmström P, Memeo L, Isola J, Bendahl PO, Rosen N, Hibshoosh H, Ringnér M, Borg A, Parsons R. Proc Natl Acad Sci U S A. 2007 May 1;104(18):7564-9.
  • Targeting the NF-kappaB signaling pathway in Notch1-induced T-cell leukemia. Vilimas T, Mascarenhas J, Palomero T, Mandal M, Buonamici S, Meng F, Thompson B, Spaulding C, Macaroun S, Alegre ML, Kee BL, Ferrando A, Miele L, Aifantis I. Nat Med. 2007 Jan;13(1):70-7.
  • NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth. Palomero T, Lim WK, Odom DT, Sulis ML, Real PJ, Margolin A, Barnes KC, O'Neil J, Neuberg D, Weng AP, Aster JC, Sigaux F, Soulier J, Look AT, Young RA, Califano A, Ferrando AA. Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18261-6. Erratum in: Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4240.
  • Activating Notch1 mutations are an early event in T-cell malignancy of Ikaros point mutant Plastic/+ mice. Mantha S, Ward M, McCafferty J, Herron A, Palomero T, Ferrando A, Bank A, Richardson C. Leuk Res. 2007 Mar;31(3):321-7.
  • Transcriptional regulatory networks downstream of TAL1/SCL in T-cell acute lymphoblastic leukemia. Palomero T, Odom DT, O'Neil J, Ferrando AA, Margolin A, Neuberg DS, Winter SS, Larson RS, Li W, Liu XS, Young RA, Look AT. Blood. 2006 Aug 1;108(3):986-92.
  • Regulation of T-cell progenitor survival and cell-cycle entry by the pre-T-cell receptor. Aifantis I, Mandal M, Sawai K, Ferrando A, Vilimas T. Immunol Rev. 2006 Feb;209:159-69.

Click here to view Dr. Ferrando's profile.

Anne Gershon, MD

Academic Title(s):

Director, Division of Pediatric Infectious Diseases
Professor of Pediatrics

Contact Information:

Tel: (212) 305-9445
Fax: (212) 342-1578
Email: aag1@columbia.edu

Research

The research activities of Dr. Gershon's group include the study of immunity to varicella (chickenpox) and herpes zoster (shingles) Dr. Anne Gershon research has included epidemiology, diagnosis, immunology, latency, prevention, and treatment of varicella and zoster virus infections. Her studies with varicella vaccine, which examined the safety and efficacy of the vaccine in leukemic children and adults, were crucial to its licensure; the vaccine is now recommended for all healthy children in the United States. She is continuing to study the safety and efficacy of varicella vaccine and the zoster vaccine in the "vaccine era". She has also focused on HIV infection in children, particularly with regard to opportunistic infections. She has research funding from the NIH to study the growth and pathogenesis of VZV in cell culture, and latency of VZV in humans and animal models. Dr. Gershon has served on the Committee on Infectious Diseases of the American Academy of Pediatrics ("Red Book" Committee) and the Committee on Immunization Practices (ACIP) of the CDC. She was a member of the CDC's Working Group for varicella vaccine and played a major role in recommending a second routine dose of the vaccine for all children. She is a member of the Councils of the Infectious Diseases Society of America (IDSA) and the Pediatric Infectious Disease Society. She is currently President of IDSA. She is the author of over 250 publications and has edited 8 books. She is a member of a March of Dimes Research Committee Study Section.

Selected Publications

  • Gershon AA, Chen J, and Gershon MD. A model of lytic, latent, and reactivating varicella-zoster virus infections in isolated enteric neurons. J Infect Dis 2008; 197 Suppl 2:S61-5.
  • Gershon, AA. Varicella-zoster virus infections. Pediatr Rev 2008; 29(1): 5-10.
  • Levin MJ, Gershon AA, Weinberg A, Song LY, Fentin T, Nowak B. Administration of live varicella vaccine to HIV-infected children with current or past significant depression of CD4(+) T cells. J Infect Dis 2006;194(2):247-55.
  • Arvin A, Gershon A. Control of varicella: why is a two-dose schedule necessary? Pediatr Infect Dis J 2006;25(6):475-6.
  • Quinlivan MA, Gershon AA, Nichols RA, La Russa P, Steinberg SP, Breuer J. Vaccine Oka varicella-zoster virus genotypes are monomorphic in single vesicles and polymorphic in respiratory tract secretions. J Infect Dis 2006;193(7):927-30.
  • Stallings CL, Duigou GJ, Gershon AA, Gershon MD, Silverstein SJ. The cellular localization pattern of Varicella-Zoster virus ORF29p is influenced by proteasome-mediated degradation. J Virol 2006;80(3):1497-512.
  • Dworkin RH, Johnson RW, Breuer J, Gershon, A. et al. Recommendations for the management of herpes zoster. Clin Infect Dis 2007;44 Suppl 1:S1-S26.
  • Quinlivan ML, Gershon AA, Al Bassam MM, et al. From the Cover: Natural selection for rash-forming genotypes of the varicella-zoster vaccine virus detected within immunized human hosts. Proc Natl Acad Sci U S A 2007;104(1):208-12.
  • Michalik DE, Steinberg SP, LaRussa PS, Edwards KM, Wright PF, Arvin AM, Gans, HA, Gershon, AA. Primary vaccine failure after 1 dose of varicella vaccine in healthy children. J Infect Dis 2008; 197(7):944-9.
  • Breuer J, Quinlivan M, Al Bassam M, Gershon, A, et al: DNA sequence variability in Oka vaccine isolates. J Infect Dis 196:801, 2007
  • Gershon AA: Vaccination to prevent zoster in the elderly. Epidemiol Infect 135:883, 2007
  • Gershon AA, Arvin AM, Shapiro E: Varicella vaccine. N Engl J Med 356:2648, 2007
  • Hambleton S, Steinberg SP, Gershon MD, Gershon, A. et al: Cholesterol dependence of varicella-zoster virion entry into target cells. J Virol 81:7548, 2007

Click here to view Dr. Gershon's profile.

Kara Gross Margolis, MD

Academic Title(s)

Assistant Professor of Clinical Pediatrics

Division(s)

Pediatric Gastroenterology

Contact Information

Tel: (212) 305-5903
Fax: (212) 342-5756
Email: kjg2133@columbia.edu

Research

Dr. Gross Margolis is a pediatric gastroenterologist whose research focuses on the role of the nervous system in the gut (the enteric nervous system), and neurotransmitters, in intestinal inflammation. Her translational research interests focus on the roles that oxytocin, serotonin and the density of enteric innervations play in inflammatory bowel disease (Crohn's disease and ulcerative colitis) and necrotizing enterocolitis. She is also a site principal investigator on a multi-center clinical study examining the prevalence of gastrointestinal conditions in children with autism. Her clinical interests include intestinal inflammatory disorders (Crohn's disease, ulcerative colitis, eosinophilic esophagitis and celiac disease) as well as gastrointestinal conditions in children with autism.

Selected Publications

  • Margolis KG and Gershon MD. Neuropeptides and Inflammatory Bowel Disease. Curr Opin Gastroenterol. 2009 Nov;25(6):503-11.
  • Margolis KG and Pothoulakis C. Serotonin has a Critical Role in the Pathogenesis of Experimental Colitis. Gastroenterology .2009 Nov;137(5):1562-6.
  • Gross K, Karagiannides I, Koon HW, Bowe C, Kim H, Thomou T, Giorgadze N, Tchkonia T, Kirkland J,and Pothoulakis C. Substance P Promotes Expansion of Human Mesenteric Preadipocytes Through Proliferative and Anti-Apoptotic Pathways. Am J Physiol Gastrointest Liver Physiol. 2009 May;296(5):G1012-9.
  • Welch MG, Tamir h, Gross KJ, Anwar M, and Gershon MD. Expression and developmental regulation of oxytocin and oxytocin receptors in the enteric nervous system and intestinal epithelium. J Comp Neurol. 2009 Jan 10;512(2):256-70.
  • Welch MG, Anwar M, Chang CY, Gross KJ, Ruggiero DA, Tamir H, Gershon MD. Combined administration of secretin and oxytocin inhibits chronic colitis and associated activation of forebrain neurons. Neurogastroenterology and Motility. 2010 Jun. 22(6)654-e202.
  • Li ZS, , Blakely R, Margolis KG and Gershon MD. The Role of Tryptophan Hydroxylase in Dopaminergic Development in the Enteric Nervous System. Accepted to Journal of Neuroscience.
  • Gross, KJ and Pothoulakis C. The Role of Neuropeptides and the Immune System: A Potential Role in Inflammatory Bowel Disease (IBD). IBD Journal 2007; 13(7): 918-32.
  • Lenders C and Gross KJ. Pediatric Overweight and Micronutrient Deficiency. Presented at the workshop "Dealing With Co-morbidities of Pediatric Overweight" with the American Academy of Pediatrics.April 2005.
  • Van Schaik SM, Obot N, Enhorning G, Hintz K, Gross KJ, Hancock GE, Stack AM, and Welliver RC, Gross KJ et al. The Role of Interferon Gamma in the Pathogenesis of Primary Respiratory Synctial Virus Infection in BALB/C Mice.Journal of Medical Virology 2000; 62(2):257-266.
  • Borowitz D, Cerny F, Zallen G, Sharp J, Burke M, Gross K, and Glick P. Is the Nuss Procedure Associated with Improved Exercise Capacity? Journal of Pediatric Surgery 2002; 34(3): 123 -132.

Click here to view Dr. Gross Margolis's profile.

James Jarvis, MD

Academic Title(s)

Professor of Clinical Pediatrics

Division(s)

Pediatric Rheumatology

Contact Information

Tel: (212) 305-1341
Email: jj2583@columbia.edu

Research

We are interested in how genomes function in the setting of chronic inflammation. As projects such as NIH’s ENCODE (Encyclopedia of DNA Elements- http://www.genome.gov/10005107) have shown us, the human genome is a busy and interesting place. Rather than being a passive template from which proteins are made, the genome is a dynamic, active region of the cell that reads and responds to the external environment and is even able to read and regulate itself. We are particularly interested in how gene transcription is regulated and coordinated on a genome-wide basis.
Current projects include the development of gene-array based biomarkers for response to therapy in juvenile idiopathic arthritis (R01-AR-060604, Microarray-Based Biomarkers in Juvenile Idiopathic Arthritis) and the examination of epigenetic regulators of transcriptional control in human leukocytes. These projects are being undertaken in collaboration with colleagues in the Center for Computational Biology and Bioinformatics (C2B2 - http://www.c2b2.columbia.edu/?q=node/5) here at the Columbia University Medical Center.

Selected Publications

  • Knowlton N, Jiang K, Frank MB, Aggarwal A, Wallace C, McKee R, Chaser B,Tung C, Smith L, Chen Y, OsbanJ, O¹Neil K, Centola M, McGhee JL, Jarvis JN, The meaning of clinical remission in polyarticular juvenile idiopathic arthritis: gene expression profiling in peripheral blood mononuclear cells identifies distinct disease states. Arthritis Rheum 2009; 60: 892-900.
  • Frank MB, Wang S, Aggarwal A, Knowlton N, Jiang K, Chen Y, McKee R, Chaser B, McGhee T, Osban J, Jarvis JN, Disease-associated pathophysiologic structures in pediatric rheumatic diseases show characteristics of scale-free networks seen in physiologic systems: implications for pathogenesis and treatment. BMC Med Genomics 2009; 2: 9.
  • Jarvis JN, Jiang K, Frank MB, Knowlton N, Aggarwal A, Wallace CA, McKee R, Chaser B, Tung C, Smith LB, McGhee JL, Chen Y, Osban J, O¹Neil KN, Centola M, Gene expression profiling in neutrophils of children with polyarticular juvenile idiopathic arthritis. Arthritis Rheum 2009; 60: 1488-1495.
  • Dozmorov IM, Jarvis J, Saban R, Benbrook DM, Wakeland E, Asentijevich I, Ryan J, Chiorazzi N, Gutheridge JM, Drewe E, Tighe PJ, Centola M, Lefkowits I, Internal standard-based analysis of microarray data 2 ­Analysis of functional associations between HVE genes. Nucleic Acids Res 2011; 1-19.

Rachel L. Miller M.D. FAAAAI

Academic Title(s)

Director, Division of Allergy and Immunology
Associate Professor of Medicine (In Pediatrics) and Environmental Health Sciences

Division(s)

Medicine, Pediatrics, EHS/Pulmonary, Allergy and Critical Care Medicine

Contact Information

Tel: (212) 305-7759
Fax: (212) 305-2277

Research

Dr. Miller's work concentrates on the mechanisms for the onset of asthma. One large research focus involves establishing and studying a birth cohort from Northern Manhattan (CCCEH.org), determining the importance of environmental allergens, traffic-related pollutants, and phthalate exposure to the onset of allergies, asthma, and Th2 immune responses. A major emphasis is on the role of prenatal and early postnatal exposure on later pediatric and adolescent asthma risk. Additional areas of research include identifying novel genetic by environment interactions and epigenetic by environment interactions important to the onset of asthma. We also have established several mouse models examining the importance of prenatal and postnatal environmental exposures on asthma risk. Recent work on antigen-specific immune responses to influenza vaccine in utero was cited by the journals Nature and Science on their website. In the last several years, Dr. Miller has been building a program in environmental epigenetics and asthma by studying DNA methylation in cell, mouse and human systems.

Selected Publications

  • Rastogi, D., Chaodong Wang, Xia Mao, Cynthia Lendor, Paul B. Rothman, Rachel L. Miller. Antigen-specific immune responses to influenza vaccine in utero, Journal of Clinical Investigation, 117 (6):1637-46, 2007.
  • Liu, Jinming, Manisha Ballaney, Umaima Al-alem, Chunli Quan, Ximei Jin, Frederica Perera, Lung-Chi Chen, Rachel L. Miller. Combined inhaled diesel exhaust particles and allergen exposure alter methylation of T helper genes and IgE production in vivo, Toxicological Sciences, 102 (1), 76-81, 2008.
  • Perzanowski, M.S., GL Chew, A Divjan, K Panjwani, A Johnson, BJ Sheares, IF Goldstein, TA Platts-Mills, FP Perera, RL Miller. Cat ownership is a risk factor for developing anti-cat IgE but not current wheeze at age 5 in a low income urban NYC cohort, Journal of Allergy and Clinical Immunology, 121:1047-52, 2008.
  • Miller, R. L., Ho, S.-m. Epigenetic studies should focus on specific cell types. Am J Respir Crit Care Med. 178:883-883, 2008, letter.
  • Donohue, Kathleen M., Umaima Al-alem, Matthew S. Perzanowski, Ginger L. Chew, Alina Johnson, Adnan Divjan, Elizabeth A. Kelvin, Lori A. Hoepner, Frederica P. Perera, Rachel L. Miller, Anti-cockroach, mouse IgE is associated with early wheeze and atopy in an inner-city birth cohort, Journal of Allergy and Clinical Immunology, 122(5):914-20, 2008.
  • Perera F, W-Y Tang W-Y, JB Herbstman, DT Tang, L Levin, RL Miller and S-M Ho. Relation of DNA methylaton status of ACSL3 to transplacental exposure to airborne polycyclic aromatic hydrocarbons and childhood asthma. PlosOne, 4(2) February 2009.
  • Patel, Molini M., Lori Hoepner, Robin Garfinkel, Steven Chillrud, Andria Reyes, Frederica Perera, Rachel L. Miller Ambient metals and elemental carbon in fine particulate matter predict wheeze and cough in very young urban children, American Journal of Respiratory and Critical Care Medicine, 180 (11):1107-1113. 2009.
  • Perzanowski, Matthew S., Rachel L. Miller, Deliang Tang, David Ali, Robin S. Garfinkel, Ginger L. Chew, Inge F. Goldstein, Frederica P. Perera, R. Graham Barr. Prenatal acetaminophen exposure and risk of wheeze at age 5 years in an urban, low-income cohort, Thorax, 65 (2): 118-23, 2010.
  • Rachel L. Miller, Robin Garfinkel, Cynthia Lendor, Lori Hoepner, Zheng Li, Lovisa Romanoff, Andreas Sjodin, Larry Needham, Frederica P. Perera, Robin M Whyatt. Polycyclic aromatic hydrocarbon metabolite levels and pediatric asthma-related outcomes in an inner city cohort. Pediatric Allergy and Immunology, 21:260-267, 2010.
  • Maria Jose Rosa, Kyung Hwa Jung, Matthew S. Perzanowski, Elizabeth A. Kelvin, Katherine W Darling, David Camann, Steven N Chillrud, Robin M Whyatt, Patrick L Kinney, Frederica P. Perera, Rachel L. Miller. Prenatal exposure to polycyclic aromatic hydrocarbons, environmental tobacco smoke and asthma in young children, Respiratory Medicine, 105:869-76, 2011
  • Marilyn Reyes, Matthew S. Perzanowski, Robin M. Whyatt, Elizabeth A. Kelvin, Andrew G. Rundle, Diurka Diaz, Beatriz Plaza, Lori Hoepner, Frederica P. Perera, Virginia Rauh, Rachel L. Miller. Maternal demoralization is associated with childhood wheeze, but not IgE, at age five years in an inner-city cohort, Annals of Allergy, Asthma & Immunology, 107 (1): 42-49, 2011.
  • Justin Mostecki, Walter T. Klimecki, Debra A. Stern, Suzanne L. Cassel, Lizhi Yu, Judit Knisz, Penelope Graves, Rachel L. Miller, Brian M. Showalter, Maartje van Peer, James Russo, Marilyn Halonen, Fernando D. Martinez, Donata Vercelli and Paul B. Rothman. A SOCS-1 Promoter Variant is associated with total serum IgE level, J. Immunology, 187 (5):2794-802 , 2011.
  • Phillip Factor, Alexander Akhmedov, Jake MacDonald, Anna Xu, Jie Wu, Trisha Das, Raymond Panettieri, Frederica Perera, and Rachel L. Miller. Polycyclic aromatic hydrocarbons impair b2AR function in airway epithelial and smooth muscle cells, The American Journal of Respiratory Cell and Molecular Biology, 45: 1045-1049, 2011.
  • Rachel L. Miller and Cara L. Agerstrand. Targeting indoor air pollution: Interpreting the RESPIRE trial, The Lancet, 378:1682-83, 2011
  • DZ Torrone, JS Kuriakose, K Moors, H Jiang, M Niedzwiecki, F Perera, RL Miller. Reproducibility and intra-individual variation over days in buccal cell DNA methylation of two asthma genes, interferon gamma (IFN-?) and inducible nitric oxide synthase (iNOS), Clinical Epigenetics, 4:3, 2012.
  • Stephanie Lovinsky-Desir and Rachel L. Miller. Epigenetics, asthma and allergic diseases: A review of latest advancements. Current Allergy and Asthma Reports, 2012, in press.

Click here to view Dr. Miller's profile.

Alice Prince, MD

Academic Title(s):

Professor of Pediatrics (in Pharmacology)

Division(s):

Contact Information:

Pediatric Infectious Disease

Tel: (212) 305-4193
Fax: (212) 342-5728
Email: asp7@columbia.edu

Research

Dr. Prince's laboratory studies the interaction of bacterial pathogens and the airway epithelium, a component of the mucosal immune system that initiates the host response to infection. We use multi-disciplinary approaches to identify key components of bacterial pathogens that are critical in the pathogenesis of airway infection and the nature of the epithelial signaling cascade that recruits inflammatory cells into the lung. As much of the pathology of pneumonia is due to the host response to infection, we have focused upon the host response to bacterial components, and how this response is regulated. A major area of interest has been the pathogenesis of airway infection in cystic fibrosis and we have focused our research on two common CF pathogens, Pseudomonas aeruginosa and Staphylococcus aureus and how they interact with both CF and normal airway epithelial cells. A major area of research has been the identification of epithelial receptors that initiate chemokine production (IL-8) in response to bacterial gene products. While few organisms are actually adherent to airway epithelial cells, bacterial components ligate TLR2 exposed on the apical surface of airway cells in a lipid raft complex along with asialoGM1, which provides a ligand for many pulmonary pathogens. TLR signaling, NF-kB and MAPK activation initiates chemokine expression to signal the influx of phagocytes to the site of infection. TLR2 signaling also activates a number of secondary messengers including Ca2+ fluxes. Following TLR2 phosphorylation by cSrc, Ca2+ fluxes are generated that can activate adjacent epithelial cells through gap junctions or connexins, a response that is also regulated by cSrc kinases. The Ca2+ fluxes also activate calpains, proteases that are involved in modulating the epithelial barrier to facilitate the transmigration of phagocytes into the airway. In addition, we study the bacterial virulence factors that target epithelial cells. Having explored some of the immunostimulatory properties of flagella and pili, we are now interested in gene products that affect the integrity of the epithelial barrier. The type 3 toxins of P. aeruginosa, for example, are important in modifying epithelial tight junctions to facilitate invasive infection. Ongoing projects are focusing upon the identification of the epithelial junctional proteins that are altered in response to bacterial ligands. Staphylococcus aureus and particularly MRSA infections have become a major public health issue. Using the same approach, using wild type and mutant strains of S. aureus and comparing the signaling pathways that they activate in vitro in airway epithelial cells and in vivo in transgenic mice, we have identified protein A as a major virulence factor in the pathogenesis of pneumonia. Having demonstrated that protein A stimulates TNFa signaling, we are now localizing domains of the protein that independently activate type I interferon signals.
In addition to S. aureus, we have also determined that S. pneumoniae and other respiratory pathogens also activate epithelial type I interferon signaling. It apears that each of these mucosal pathogens has its own mechanism to induce IFN-B expression, some stimulate via TLR4 from within the context of an endosome, others use pore forming toxins to deliver gene products intracellularly. Current projects are dissecting how these mucosal pathogens each activate type I IFN responses and how this contributes to pathogenesis. These projects are supported by the NIH.

Selected Publications:

  • Martin FJ, Gomez MI, Wetzel D, Memmi, G, O’Seaghdha, M, Soong, G, Schindler C, Prince AS. S. aureus activates type I IFN signaling in mice and humans through the Xr repeated sequences of protein A. J. Clin. Invest. 119(7):1931-9, 2009. PMCID: PMC2701857
  • Jarin Chun and Alice Prince. TLR2-induced calpain cleavage of epithelial junctional proteins facilitates leukocyte transmigration. Cell Host and Microbe. 2009 Jan 22;5(1):47-58.
  • Francis Martin and Alice Prince. TLR2 Regulates Gap Junction Intercellular Communication in Airway Cells. J Immunol. 2008 Apr 1;180(7):4986-93.
  • Grace Soong, Parker D, Magargee M, Prince AS. The type III toxins of P. aeruginosa disrupt epithelial barrier function. J Bacteriol. 2007 Dec 2
  • Marisa Gomez and Alice Prince. Opportunistic infections in lung disease: Pseudomonas infections in cystic fibrosis. Curr Opin Pharmacol. 2007 Jun;7(3):244-51.Apr 5.
  • Valerie Waters, Gomez MI, Soong G, Amin S, Ernst R, Prince A. Immunostimulatory properties of the emerging pathogen Stenotrophomonas maltophilia.Infect Immun. 2007 Apr;75(4):1698-703.
  • Marisa Gomez, O'Seaghdha MO, Prince AS. Staphylococcus aureus protein A activates TACE through EGFR-dependent signaling. EMBO J. 2007 Feb 7;26(3):701-9.
  • Marisa Gomez, O'Seaghdha M, Magargee M, Foster TJ, Prince A. Staphylococcus aureus protein A activates TNFR1 signaling through conserved IgG binding domains. J Biol Chem. 281:20190-20196, 2006.
  • Grace Soong, A Muir, MI Gomez, J Waks, B Rheddy, P Planet, P Singh, Y Kaneko, MC Wolfgang, YS Hsiao, L Tong, A Prince. Bacterial neuraminidase facilitates mucosal infection by participating in biofilm production. J Clin Invest. 116: 2297-2305, 2006
  • Alice Prince, Mizgerd, J, Wiener-Kronish, JP , Bhattacharya, J. Cell signaling underlying the pathophysiology of pneumonia. Am J Physiol Lung Cell Mol Physiol. 2006 Sep;291(3):L297-300.
  • Jarin Chun and Alice Prince Activation of Ca2+-dependent signaling by TLR2. J Immunol. 177:1330-1337. 2006. Alice Prince. Flagellar activation of epithelial signaling. Am J Resp Cell Molec Biol 34:548-551, 2006.

Click here to Visit Dr. Prince's website.

Click here to view Dr. Prince's profile.

Adam J. Ratner, MD, MPH

Academic Title(s):

Florence Irving Assistant Professor of Pediatrics and Microbiology & Immunology

Division(s):

Infectious Disease

Contact Information:

Tel: (212) 305-9807
Fax: (212) 342-5812
Email: ar127@columbia.edu

Research

Dr. Ratner investigates the pathogenesis of infectious diseases, with a focus on bacterial diseases affecting children. Using a variety of techniques, we are currently attempting to answer questions in four main areas:
Bacterial colonization and host range: The mucosal surfaces of humans are simultaneously colonized with a vast number of microbial species, some of which are potential pathogens. Certain members of this microbiota may colonize or infect multiple host species, while others are host-specific. What specific bacterial and host products are essential to host range in the settings of colonization and disease? Evolution and function of bacterial toxins: Many bacterial pathogens of humans produce protein toxins that damage or kill host cells at high concentrations. However, it is advantageous for the host to recognize these products while they are at low density and to initiate immune responses before lethal toxin concentrations are present. How do host cells detect and respond to sublethal concentrations of bacterial toxins? How can we most efficiently identify and characterize new toxins and understand their evolution? Infectious causes of preterm birth: Premature birth is a major cause of pediatric morbidity and mortality worldwide, but its causes are poorly understood. Several infectious diseases, including bacterial vaginosis, urinary tract infection, and chorioamnionitis, increase the risk of premature birth. We are attempting to model these conditions in an effort to better understand the link between infection and prematurity and to develop and evaluate targeted diagnostics and interventions. Epidemiology of pediatric infectious diseases: How do interventions (vaccination, screening and treatment programs) change the epidemiology of both targeted and untargeted diseases within populations? What can we expect as new interventions are approved and used?

Selected Publications

  • Aguilar JA, Kulkarni R, Randis TM, Soman S, Kikuchi A, Yin Y, Ratner AJ. Phosphatase-Dependent Regulation of Epithelial Mitogen-Activated Protein Kinase Responses to Toxin-Induced Membrane Pores. PLoS ONE 2009; 4(11): e8076.
  • Shah SS, Wood SM, Luan X, Ratner AJ. Decline in varicella-related ambulatory visits and hospitalizations since routine immunization against varicella. Pediatr Infect Dis J 2010; (Epub Nov 25 2009).
  • Wood SM, Shah SS, Bafana M, Ratner AJ, Meaney PA, Malefho KC, Steenhoff AP Epidemiology of methicillin-resistant Staphylococcus aureus bacteremia in Gaborone, Botswana.. Infect Control Hosp Epidemiol. 2009 Aug;30(8):782-5.
  • Lehrer RI, Jung G, Ruchala P, Wang W, Micewicz ED, Waring AJ, Gillespie EJ, Bradley KA, Ratner AJ, Rest RF, Lu W. Human alpha-defensins inhibit hemolysis mediated by cholesterol-dependent cytolysins. Infect Immun. 2009;77(9):4028-40.
  • Randis TM, Kulkarni R, Aguilar JL, Ratner AJ. Antibody-based detection and inhibition of vaginolysin, the Gardnerella vaginalis cytolysin. PLoS ONE 2009; 4(4): e5207.
  • Gelber SE, Aguilar JL, Lewis KL, Ratner AJ. Functional and phylogenetic characterization of vaginolysin, the human-specific cytolysin from Gardnerella vaginalis. J Bacteriol 2008; 190(11): 3896-3903.
  • Ratner AJ, Aguilar JL, Shchepetov M, Lysenko ES, Weiser JN. Nod1 mediates cytoplasmic sensing of combinations of extracellular bacteria. Cell Microbiol 2007; 9: 1343-1351.
  • Ratner AJ, Hippe KR, Aguilar JL, Bender MH, Nelson AL, Weiser JN. Epithelial cells are sensitive detectors of bacterial pore-forming toxins. J Biol Chem 2006; 281: 12994-8.
  • Shah SS, Ratner AJ. Trends in invasive pneumococcal disease-associated hospitalizations. Clin Infect Dis 2006; 42: e1-5.

Click here to visit Dr. Ratner's website.

Click here to view Dr. Ratner's profile.

Thyyar Ravindranath, MD

Academic Title(s):

Assistant Professor of Clinical Pediatrics

Division(s):

Pediatric Critical Care

Contact Information:

Tel: (212)305-8458
Fax: (212) 342-2293
Email: tr2148@columbia.edu

Research

His research has involved understanding the pathophysiology and cell signaling pathways following bacterial infection in rodent models consisting of both rat and transgenic mice. His initial studies entailed adaptive immune response in gastrointestinal tract following sepsis in rats. Recent work includes the role of aldo-ketoreductase in polymicrobial sepsis induced acute lung inflammation as well as in chronic inflammation following diabetes and atherosclerosis, cerebral mitochondrial dysfunction following systemic inflammatory response in mice and studying the adaptive immunological responses in infants and children following acute respiratory failure secondary to viral lower respiratory tract inflammation.

Selected Publications

  • T. M. Ravindranath Phyllus Y. Mong, Radha Ananthakrishnan, Qing Li, Nosirudeen Quadri, Ann Marie Schmidt, Ravichandran Ramasamy, and Qin Wang. Novel role for aldose reductase in mediating acute inflammatory responses in the lung. J Immunol 2009 183: 8128-8137
  • T.M. Ravindranath, Goto M. Iqbal O. Florian-Kujawski M. Hoppensteadt D. Hammadeh R. Sayeed MM. Fareed J. Plasma Thrombin Activatable Fibrinolysis Inhibitor (TAFI) and Tissue Factor Pathway Inhibitor (TFPI) Changes following sepsis. Clinical and Applied Thrombosis/Hemostasis 2007, 13 (4):362-368
  • Goto M. Samonte V, Ravindranath T, Sayeed MM, Gamelli RL. Burn injury exacerbates hemodynamic and metabolic responses in rats with polymicrobial sepsis. Journal of Burn Care & Research. 27(1):50-9, 2006

Click here to view Dr. Ravindranath's profile.

Steven L. Reiner, M.D. MPH

Academic Title(s):

Professor of Microbiology & Immunology and Pediatrics

Division(s):

Microbiology and Immunology

Contact Information:

Tel: (212) 305-5177
Email: sreiner@columbia.edu

Research

Upon engagement in an immune response, a naive T lymphocyte undergoes a program of rapid proliferation and many of its cellular progeny undergo terminal effector differentiation. After an immune response has ended, some antigen-specific daughter cells remain as long-lived replicas of the useful clone, so-called memory cells, which form the basis for successful vaccination. Using lymphocytes as a model system, we have provided evidence that asymmetric cell division may be a way for many mobile, non-polarized cells to generate cell fate diversity among their progeny. We are using static and time-lapsed imaging, genetic, and biochemical methods to better understand the nature and extent of asymmetric cell division in multi-celled beings. It is predicted that this will have immediate relevance for the way in which blood stem cells and metastatic cancer stem cells can generate diverse progeny despite their lack of obvious polarity. Studies of lymphocyte differentiation during the immune response should continue to become an increasingly useful model for inquiry into the fundamental problem of regulated gene expression in dividing, differentiating, and highly mobile cells.

Selected Publications

  • Gordon, S.M., J. Chaix, L.J. Rupp, J. Wu, S. Madera, J.C. Sun, T. Lindsten, and S.L. Reiner. (2012) The transcription factors T-bet and Eomes control key checkpoints of natural killer cell maturation. Immunity 2012:36:55-67
  • Barnett, B.E., M.L. Ciocca, R. Goenka, L.G. Barnett, J. Wu, T.M. Laufer, J.K. Burkhardt, M.P. Cancro and S.L. Reiner. (2012) Asymmetric B cell division in the germinal center reaction. Science 335: 342-344.
  • Chang, J.T., M.L. Ciocca, I. Kinjyo, V.R. Palanivel, C.E. McClurkin, C.S. DeJong, E.C. Mooney, J.S. Kim, N.C. Steinel, J. Oliaro, C.Y. Yin, B.I. Florea, H.S. Overkleeft, L.J. Berg, S.M. Russell, G.A. Koretzky, M.S. Jordan and S.L. Reiner. (2011) Asymmetric proteasome segregation as a mechanism for unequal partitioning of the transcription factor T-bet during T lymphocyte division. Immunity 34: 492-504.
  • Banerjee, A., S.M. Gordon, A.M. Intlekofer, M.A. Paley, E.C. Mooney, T. Lindsten, E.J. Wherry, and S.L. Reiner. (2010) Cutting Edge: The transcription factor Eomesodermin enables CD8+ T cells to compete for the memory cell niche. J. Immunol. 185: 4988-4992.
  • Kinjyo, I., S.M. Gordon, A.M. Intlekofer, K. Dowdell, E.C. Mooney, R. Caricchio, S.A. Grupp, D.T. Teachey, V.K. Rao, T. Lindsten and S.L. Reiner. (2010) Cutting edge: lymphoproliferation caused by fas deficiency is dependent on the transcription factor eomesodermin. J. Immunol. 185: 7151-7155.
  • Intlekofer, A.M., A. Banerjee, N. Takemoto, S.M. Gordon, C.S. Dejong, H. Shin, C.A. Hunter, E.J. Wherry, T. Lindsten and S.L. Reiner. (2008) Anomalous type 17 response to viral infection by CD8+ T cells lacking T-bet and eomesodermin. Science 321: 408-411.
  • Chang, J.T., V.R. Palanivel, I. Kinjyo, F. Schambach, A.M. Intlekofer, A. Banerjee, S.A. Longworth, K.E. Vinup, P. Mrass, J. Oliaro, N. Killeen, J.S. Orange, S.M. Russell, W. Weninger and S.L. Reiner. (2007) Asymmetric T lymphocyte division in the initiation of adaptive immune responses. Science 315: 1687-1691.
  • Intlekofer, A.M., N. Takemoto, C. Kao, A. Banerjee, F. Schambach, J.K. Northrop, H. Shen, E.J. Wherry and S.L. Reiner. (2007) Requirement for T-bet in the aberrant differentiation of unhelped memory CD8+ T cells. J. Exp. Med. 204: 2015-2021.
  • Takemoto, N., A.M. Intlekofer, J.T. Northrup, E.J. Wherry and S.L. Reiner. (2006) Cutting Edge: IL-12 inversely regulates T-bet and eomesodermin expression during pathogen-induced CD8+ T cell differentiation. J. Immunol. 177: 7515-7519.
  • Intlekofer, A.M., N. Takemoto, E.J. Wherry, S.A. Longworth, J.T. Northrup, V.R. Palanivel, A.C. Mullen, C.R. Gasink, S.M. Kaech, J.D. Miller, L. Gapin, K. Ryan, A.P. Russ, T. Lindsten, J.S. Orange, A.W. Goldrath, R. Ahmed and S.L. Reiner. (2005) Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin. Nature Immunology 6: 1236-1244.
  • Pearce, E.L., A.C. Mullen, G.A. Martins, C.M. Krawczyk, A.S. Hutchins, V.P. Zediak, M. Banica, C.B. DiCioccio, D.A. Gross, C.A. Mao, H. Shen, N. Cereb, S.Y. Yang, T. Lindsten, J. Rossant, C.A. Hunter and S.L. Reiner. (2003) Control of effector CD8+ T cell function by the transcription factor Eomesodermin. Science 302: 1041-1043.
  • Hutchins, A.S., A.C. Mullen, H.W. Lee, K.J. Sykes, F.A. High, B.D. Hendrich, A.P. Bird and S.L. Reiner. (2002) Gene silencing quantitatively controls the function of a developmental trans-activator. Mol. Cell 10: 81-91.
  • Mullen, A.C., A.S. Hutchins, F.A. High, H.W. Lee, K.J. Sykes, L.A. Chodosh and S.L. Reiner. (2002) Hlx is induced by and genetically interacts with T-bet to promote heritable T(H)1 gene induction. Nature Immunology 3: 652-658.
  • Mullen, A.C., F.A. High, A.S. Hutchins, H.W. Lee, A.V. Villarino, D.M. Livingston, A.L. Kung, N. Cereb, T.P. Yao, S.Y. Yang and S.L. Reiner. (2001) Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Science 292: 1907-1910.
  • Mullen, A.C., A.S. Hutchins, A.V. Villarino, H.W. Lee, F.A. High, N. Cereb, S.Y. Yang, X. Hua and S.L. Reiner. (2001) Cell cycle controlling the silencing and functioning of mammalian activators. Curr. Biol. 11: 1695-1699.
  • Bird, J.J., D.R. Brown, A.C. Mullen, N.H. Moskowitz, M.A. Mahowald, J.R. Sider, T.F. Gajewski, C.R. Wang and S.L. Reiner. (1998) Helper T cell differentiation is controlled by the cell cycle. Immunity 9: 229-237.

Click here to view Dr. Reiner's profile.

Robert Winchester, MD

Academic Title(s):

Professor

Division(s):

Rheumatology

Contact Information:

Tel: (212) 305-8250
Email: rjw8@columbia.edu

Research

A long-standing interest of the Winchester laboratory is to understand the relationship between MHC molecules and the T cell in autoimmunity. One major area of research is concerned with delineating the heterogeneity in pathways of tissue injury in the glomerulonephritis of systemic lupus erythematosus using laser capture microdissection and microarray approaches on clinical renal biopsies to characterize the transcriptional phenotype of lupus nephritis. Evidence has been obtained that while class III or IV nephritis are not distinguishable at the molecular level, there is considerable molecular heterogeneity in the glomerular injury processes in lupus, with one subset of patients characterized by abundant TNF-alpha and monocyte chemotactic protein-1 that is associated with evidence of glomerulosclerosis and extensive interstitial T cell infiltration, while another subset lacks these markers and is associated with a more benign pathologic appearance. Moreover, the changes in gene expression appear to reflect extensive and coordinated reprogramming, including the presence of transcripts that appear inappropriate for the developmental stage. A related area of study uses the same laser capture microdissection approach to examine the T cell traffic and extent of clonal expansion comprising the interstitial T cell infiltration in the subset of lupus kidneys with developing glomerulosclerosis. In a number of instances the same expanded T cell clone is identified in periglomerular interstitium or in two or more anatomically separate locations within the biopsies. In one case the identical predominant T cell clone was identified in the CD8 T cell subset of the blood and in two kidney biopsies separated by 6 years, suggesting a relationship to the progression of renal impairment.
A newer area of work is delineating the importance of immune mechanisms in mediating the events of calcific aortic stenosis. Previously calcific (senile) aortic stenosis had been considered a "degenerative" disease for which the only therapy was valve replacement surgery, however the valve-infiltrating T cells were found to be clonally expanded, activated and differentiated to memory effector status. The mechanisms of valve injury in calcific aortic stenosis appears to have many analogies with those found in the some rheumatic diseases and suggest that this disease may be mediated by an autoimmune type of injury. Recently considerable activation and clonal expansion of circulating T cells was identified in these cases, paralleling the events in the valve, with sharing of certain expanded clones between the blood and the valve. The long-range goals of both projects is to isolate representative clones and using molecular biologic techniques identify the peptides that trigger the clones and determine the extent to which the memory-effector T cells respond to signals of tissue stress.

Selected Publications

  • The lymphocytic infiltration in calcific aortic stenosis predominantly consists of clonally expanded T cells. Wu HD, Maurer MS, Friedman RA, Marboe CC, Ruiz-Vazquez EM, Ramakrishnan R, Schwartz A, Tilson MD, Stewart AS, Winchester R. J Immunol. 2007 Apr 15;178(8):5329-39.
  • Reshaping Cinderella's slipper: the shared epitope hypothesis. Winchester R. Arthritis Res Ther. 2006;8(3):109.

Shan Zha, MD, PhD

Academic Title(s):

Assistant Professor of Pediatrics Pathology & Cell Biology (in the Institute for Cancer Genetics)

Division(s):

Pediatric Oncology
Institute for Cancer Genetics, Dpt of Pathology

Contact Information:

Tel: (212) 851-4779
Email: sz2296@columbia.edu

Research

Dr. Zha's laboratory studies DNA repair protein in lymphocyte specific double stand break repair and lymphocyte development
DNA damage occurs frequent in living cells. Breaks at the both strands of the DNA helix – DNA double strand breaks is the most severe form of DNA damage. It can happen during DNA replication, as a result of exposure to metabolic by products (e.g. reactive oxygen species) or environmental insults (e.g. radiation), or as programmed events required for lymphocyte development, specifically V(D)J recombination during the assembly of antigen receptor genes and Class Switch Recombination during B cell maturation. While those programmed DNA double strand break events are essential for the diversity and potency of adapted immune system, mistakes in resolving those programmed DNA double strand breaks often lead to large chromosome rearrangement such as translocation, gene amplification and deletions, which are the hallmarks of lymphoma and leukemia. As a result, human patients with mutations in DNA double strand break response and repair genes are often immune deficient and are predisposed to lymphoid malignancy. The lab is interested in understanding how mammalian cells sense DNA double stand breaks, integrate cell cycle progression and cellular survival to facilitate high-fidelity repair and to prevent oncogenic transformation. In particular we are interested: 1) the functional interaction between ATM kinase and non-homologous end joining pathway; 2) how DNA double strand break repair is regulated through out cell cycles; 3) how defects in DNA double stand break repair affect lymphocyte development and development of lymphomas. In the context, Dr. Zha has developed novel mouse models using gene-targeting, based on conditional inaction of ATM and other repair factors in different stage of developing lymphocytes. A broad range of laboratory approaches ranging from basic molecular genetics, biochemistry, cell biology to cytogenetic tools are applied to monitor the kinetics of DNA repair and consequence of repair deficiencies – translocations and oncogenic transformation.

Selected Publications

  • Zha S, Boboila C, Alt FW. Mre11: roles in DNA repair beyond homologous recombination. Nat Struct Mol Biol. 2009 Aug;16(8):798-800
  • Calle E, Jankovic M, Wong N, Zha S, Chen H, Difilippantonio S, Di Virgilio M, Heidkamp G, Alt FW, Nussenzweig A and Nussenzweig M. Essential Role for DNA-PKcs in DNA Double-Strand Break Repair and Apoptosis in ATM Deficient Lymphocytes. Mol Cell. 2009 May 15;34(3):285-97
  • Li G, Alt FW, Cheng HL, Brush JW, Goff PH, Murphy MM, Franco S, Zhang Y, Zha S. Lymphocyte-Specific Compensation For XLF/Cernunnos End-Joining Functions In V(D)J Recombination. Mol. Cell. 2008 Sept.5;31(5):631-40.
  • Zha S, Sekiguchi J, Brush JW, Bassing CH, Alt FW. Complementary functions of ATM and H2AX in development and suppression of genomic instability. Proc Natl Acad Sci U S A. 2008 Jul 8;105(27):9302-6.
  • Zha S, Alt FW, Cheng HL, Brush JW, Li G. Defective DNA repair and increased genomic instability in Cernunnos-XLF-deficient murine ES cells. Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4518-23.
  • Franco S, Gostissa M, Zha S, Lombard DB, Murphy MM, Zarrin AA, Yan C, Tepsuporn S, Morales JC, Adams MM, Lou Z, Bassing CH, Manis JP, Chen J, Carpenter PB, Alt FW. H2AX prevents DNA breaks from progressing to chromosome breaks and translocations. Mol Cell. 2006 Jan 20;21(2):201-14.

Click here to view Dr. Zha's profile.

Collaborative Faculty

Andrea Califano, PhD

Academic Title(s):

Professor of Biomedical Informatics

Department(s)/Division(s):

Initiative for Systems Biology

Contact Information:

Tel: (212) 851-5183
Email: califano@c2b2.columbia.edu

Research

Dr. Califano's interests reside in the assembly of gene regulatory models for cancer and stem cells that can be interrogated to elucidate mechanisms presiding over cell pathophysiology. His lab, which integrates both experimental and computational research, has pioneered the first genome-wide regulatory model of human cells and a variety of methods for the identification of master regulators of aberrant transformation and physiological differentiation/maturation events. The latter have led to the discovery of several new genes in glioma, leukemia, lymphoma, and prostate cancer that can be targeted pharmacologically to abrogate tumorigenesis. He has also developed network-based methods for the elucidation of mechanisms of action of drugs and to identify genetic alterations that contribute to the aberrant activity of master regulators. Ongoing projects in the lab aim to define the regulatory networks for various neoplastic states of the breast, ovary, prostate, germ cell, colon, and lung, for the study of pluripotency and lineage differentiation in stem cells, and for the elucidation of mechanisms associated with the onset and progression of neurodegenerative diseases.

Selected Publications

  • Della Gatta G, Palomero T, Bansal M, De Keersmaeker K, Sole X, Paietta E, Racevskis J, Wiernik PH, Rowe JM, Meijerink JP, Califano A, and Ferrando AA, Reverse engineering of oncogenic transcriptional networks in T-cell leukemia, Nature Medicine, in press
  • Sumazin, P., Yang, X., Chiu, H.S., Chung, W.J., Iyer, A., Llobet-Navas, D., Rajbhandari, P., Bansal, M., Guarnieri, P., Silva, J., and Califano, A. (2011). An Extensive MicroRNA-Mediated Network of RNA-RNA Interactions Regulates Established Oncogenic Pathways in Glioblastoma. Cell 147, 307.
  • Kruithof-de Julio, M., Alvarez, M.J., Galli, A., Chu, J., Price, S.M., Califano, A., and Shen, M.M. (2011). Regulation of extra-embryonic endoderm stem cell differentiation by Nodal and Cripto signaling. >Development 138, 3885-3895.
  • De Keersmaecker K, Real PJ, Gatta GD, Palomero T, Sulis ML, Tosello V, Van Vlierberghe P, Barnes K, Castillo M, Sole X, Hadler M, Lenz J, Aplan PD, Kelliher M, Kee BL, Pandolfi PP, Kappes D, Gounari F, Petrie H, Van der Meulen J, Speleman F, Paietta E, Racevskis J, Wiernik PH, Rowe JM, Soulier J, Avran D, Cavé H, Dastugue N, Raimondi S, Meijerink JP, Cordon-Cardo C, Califano, A, Ferrando AA. The TLX1 oncogene drives aneuploidy in T cell transformation. Nat Med. 2010 Oct 24.
  • Carro MS, Lim WK, Snyder E, Colman H, Aldape K, Lasorella A, Califano, A, and Iavarone A* (2009) A transcriptional regulatory network initiates and maintains the mesenchymal phenotype of human malignant glioma, Nature 463(7279):318-25
  • Klein U, Lia M, Crespo M, Siegel R, Shen Q, Mo T, Ambesi A, Califano A, Migliazza A, Bhagat G, and Dalla-Favera R, (2009) The DLEU2/miR-15a/16-1 cluster controls B-cell proliferation and its deletion leads to chronic lymphocytic leukemia, Cancer Cell, 2010 Jan 19;17(1):28-40.
  • Lefebvre C, Rajbhandari P, Alvarez MJ, Bandaru P, Lim WK, Sato M, Wang K, Sumazin P, Kustagi M, Bisikirska B, Basso K, Beltrao P, Krogan N, Gautier J, Dalla-Favera R, Califano A (2010) A Human B Cell Interactome Identifies MYB and FOXM1 as Master Regulators of Proliferation in Germinal Centers, Mol. Syst. Biol., 2010 Jun 8;6:377.
  • Basso K, Sumazin P, Morozov P, Schneider C, Kitagawa Y, Maute RL, Mandelbaum J, Haddad J, Chen CZ, Califano A and Dalla-Favera R (2009) “Identification of the human mature B cells miRNome,” Immunity;30(5):744-52..
  • Zhao X, D' Arca D, Lim WK, Brahmachary M, Carro MS, Ludwig T, Cardo CC, Guillemot F, Aldape K, Califano A, Iavarone A, Lasorella A (2009) The N-Myc-DLL3 cascade is suppressed by the ubiquitin ligase Huwe1 to inhibit proliferation and promote neurogenesis in the developing brain, Dev Cell;17(2):210-21.
  • Compagno M, Lim WK, Grunn A, Nandula SV, Bertoni F, Ponzoni M, Scandurra M, Califano A, Bhagat G, Chadburn A, Dalla-Favera R, and Pasqualucci L (2009) “Mutations at multiple genes cause deregulation of the NF-kB pathway in diffuse large B-cell lymphoma,” Nature;459(7247):717-21.
  • Wang K, Saito M, Bisikirska BC, Alvarez MJ, Lim WK, Rajbhandari P, Shen Q, Nemenman I, Basso K, Margolin AA, Klein U, Dalla-Favera R, & Califano A (2009) Genome-wide Identification of Post-translational Modulators of Transcription Factor Activity in Human B-Cells, Nat Biotech;27(9):829-39.
  • Mani K, Lefebvre C, Wang K, Lim WK, Basso K, Dalla-Favera R, and Califano A, (2008) “A systems biology approach to prediction of oncogenes and molecular perturbation targets in B-cell lymphomas,” Molecular Systems Biology 4:169.
  • Palomero T, Lim WK, Odom DT, Sulis ML, Real PJ, Margolin A, Barnes KC, O'Neil J, Neuberg D, Weng AP, Aster JC, Sigaux F, Soulier J, Look AT, Young RA, Califano A and Ferrando A, (2006) NOTCH1 directly regulates MYC expression and controls oncogenic cell growth, Proc. Natl. Acad. Sci USA; 103 (48): 18261-18266 NOV 28 2006. See Erratum in: Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4240 for co-Sr. authorship.
  • Basso K, Margolin A, Stolovitzky G, Klein U, Dalla-Favera R, and Califano A, (2005) Reverse engineering of regulatory networks in human B cells, Nat Genet.;37(4):382-90.

Click here to view Dr. Califano's profile.

Raphael Clynes, MD, PhD

Academic Title(s):

Associate Professor in Medicine and Microbiology at NYPH/CUMC
Attending Physician in Medical Oncology

Department(s)/Division(s):

Medicine/Pulmonary, Allergy and Critical Care Medicine

Contact Information:

Tel: (212) 305-5289
Email: rc645@columbia.edu

Research

Raphael Clynes, M.D., Ph.D., is an expert in effector functions of antibodies. Dr. Clynes has been awarded several young investigator awards including from the Arthritis Foundation and the Kimmel foundation. He is the PI on two current R01 Awards and is co-PI for the Columbia-Presbyterian TrialNet Clinical Center for Diabetes (NIDDK). He has published several seminal reports describing the cell biology and physiological importance of Fc receptors in linking the innate and adaptive response. In particular, he has published some of the key papers describing an essential role for Fc receptors for the protective capacities of tumor antibodies and the injurious consequences of immune complexes disease. Dr. Clynes' work on dendritic cells adds to the prevailing view of IgG as an effector molecule, demonstrating that opsonizing antibody promotes antigen presentation by dendritic cells and can overcome T cell tolerance in vivo. Dr. Clynes was the first to show that passive immunotherapy of cancer patients with antitumor antibodies induces active B and T cell antitumor immunity, consistent with a vaccinal effect of therapeutic monoclonal antibodies in cancer. His current work suggests dual functionality of anti-viral IgG, limiting pro-inflammatory interferon responses systemically, while enhancing the anti-viral adaptive response. He also has characterized a novel FcR-mediated pathway in which dendritic cells can activate the B cell response in a T-independent fashion.

Selected Publications

  • CD8+ T cell concentration determines their efficiency in killing cognate antigen-expressing syngeneic mammalian cells in vitro and in mouse tissues. Budhu S, Loike JD, Pandolfi A, Han S, Catalano G, Constantinescu A, Clynes R, Silverstein SC.
  • J Exp Med. 2010 Jan 18;207(1):223-35, S1-4.
  • Dominant expression of the inhibitory FcgammaRIIB prevents antigen presentation by murine plasmacytoid dendritic cells. Flores M, Desai DD, Downie M, Liang B, Reilly MP, McKenzie SE, Clynes R.nJ Immunol. 2009 Dec 1;183(11):7129-39.
  • RAGE ligation affects T cell activation and controls T cell differentiation. Chen Y, Akirav EM, Chen W, Henegariu O, Moser B, Desai D, Shen JM, Webster JC, Andrews RC, Mjalli AM, Rothlein R, Schmidt AM, Clynes R, Herold KC. J Immunol. 2008 Sep 15;181(6):4272-8.
  • Receptor for advanced glycation end products: fundamental roles in the inflammatory response: winding the way to the pathogenesis of endothelial dysfunction and atherosclerosis. Ramasamy R, Yan SF, Herold K, Clynes R, Schmidt AM. Ann N Y Acad Sci. 2008 Apr;1126:7-13.
  • Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class II. Liang B, Workman C, Lee J, Chew C, Dale BM, Colonna L, Flores M, Li N, Schweighoffer E, Greenberg S, Tybulewicz V, Vignali D, Clynes R. J Immunol. 2008 May 1;180(9):5916-26.
  • Receptor for AGE (RAGE): weaving tangled webs within the inflammatory response. Clynes R, Moser B, Yan SF, Ramasamy R, Herold K, Schmidt AM. Curr Mol Med. 2007 Dec;7(8):743-51. Review.
  • RAGE: exacting a toll on the host in response to polymicrobial sepsis and Listeria monocytogenes. Clynes R, Herold K, Schmidt AM. Crit Care. 2007;11(6):183.
  • Receptor for advanced glycation end products expression on T cells contributes to antigen-specific cellular expansion in vivo. Moser B, Desai DD, Downie MP, Chen Y, Yan SF, Herold K, Schmidt AM, Clynes R. J Immunol. 2007 Dec 15;179(12):8051-8.
  • Protective mechanisms of IVIG. Clynes R. Curr Opin Immunol. 2007 Dec;19(6):646-51.
  • Augmented HER-2 specific immunity during treatment with trastuzumab and chemotherapy. Taylor C, Hershman D, Shah N, Suciu-Foca N, Petrylak DP, Taub R, Vahdat L, Cheng B, Pegram M, Knutson KL, Clynes R. Clin Cancer Res. 2007 Sep 1;13(17):5133-43.
  • Receptor for advanced glycation end products (RAGE) in a dash to the rescue: inflammatory signals gone awry in the primal response to stress. Herold K, Moser B, Chen Y, Zeng S, Yan SF, Ramasamy R, Emond J, Clynes R, Schmidt AM. J Leukoc Biol. 2007 Aug;82(2):204-12.
  • Antigenic targeting of the human mannose receptor induces tumor immunity. He LZ, Crocker A, Lee J, Mendoza-Ramirez J, Wang XT, Vitale LA, O'Neill T, Petromilli C, Zhang HF, Lopez J, Rohrer D, Keler T, Clynes R. J Immunol. 2007 May 15;178(10):6259-67.
  • Fc gamma receptor IIB on dendritic cells enforces peripheral tolerance by inhibiting effector T cell responses. Desai DD, Harbers SO, Flores M, Colonna L, Downie MP, Bergtold A, Jung S, Clynes R. J Immunol. 2007 May 15;178(10):6217-26.
  • Antibody-enhanced cross-presentation of self antigen breaks T cell tolerance. Harbers SO, Crocker A, Catalano G, D'Agati V, Jung S, Desai DD, Clynes R. J Clin Invest. 2007 May;117(5):1361-9.
  • 1IVIG therapy: interfering with interferon-gamma. Clynes R. Immunity. 2007 Jan;26(1):4-6.
  • Mouse models of IgG- and IgM-mediated hemolysis. Schirmer DA, Song SC, Baliff JP, Harbers SO, Clynes RA, Krop-Watorek A, Halverson GR, Czerwinski M, Spitalnik SL. Blood. 2007 Apr 1;109(7):3099-107.
  • FcR-bearing myeloid cells are responsible for triggering murine lupus nephritis. Bergtold A, Gavhane A, D'Agati V, Madaio M, Clynes R. J Immunol. 2006 Nov 15;177(10):7287-95.
  • Antitumor antibodies in the treatment of cancer: Fc receptors link opsonic antibody with cellular immunity. Clynes R. Hematol Oncol Clin North Am. 2006 Jun;20(3):585-612.

Click here to view Dr. Clynes's profile.

Riccarrdo Dalla-Favera, MD

Academic Title(s):

Percy and Joanne Uris Professor of Clinical Medicine
Professor of Genetics and Development
Professor of Pathology (in the Institute for Cancer Genetics)
Director, Herbert Irving Comprehensive Cancer Center
Director, Institute for Cancer Genetics

Department(s)/Division(s):

Institute for Cancer Genetics

Contact Information:

Tel: (212) 851-5273
Email: rd10@columbia.edu

Research

Dr. Dalla-Favera's lab works on B lymphocyte development and mechanisms of transformation of B lymphocytes

Peer-Reviewed Funding

  • 5 P30 CA013696-35 (Dalla-Favera) 7/1/03 – 6/30/13

    Cancer Center Support Grant
    This grant supports the leadership of Columbia University’s laboratory, clinical, and population –based cancer research programs and the shared resources serving Columbia University’s Cancer Center members.
    Role: PI since March 1, 2005.
  • Specialized Center of Research 7017-09 (Dalla-Favera) 10/1/08 – 9/30/13
    Leukemia and Lymphoma Society
    Molecular Targets in Lymphoma
    The goal of this program is to understand the pathogenesis of B cell-derived non-Hodgkin lymphoma and improve the diagnosis and treatment of the disease. Role: Principal Investigator, Project 1 Leader, Administrative Core Leader, Genomics Core Leader
  • 5 R37 CA37295-26 (Dalla-Favera) 7/1/02 – 6/30/12
    NIH/NCI
    AIDS-Associated Lymphoproliferative Disorders
    The goal of this project is to study the molecular pathogenesis of AIDS-associated
    B-cell derived non-Hodgkin lymphoma (AIDS-NHL)
    This grant has been designated a MERIT AWARD
    Role: PI
  • 5 R01 CA107489-05 (Dalla-Favera) 5/1/04 – 4/30/10
    NIH/NCI
    Role of BCL6 Mutation in Lymphomagenesis
    The goal of this project is to investigate the role of Bcl6 hypermutation in B-NHL pathogenesis by focusing on (1) the functional consequences of BCL6 hypermutation; (2) the role of BLC6 mutations in lymphomagenesis; (3) the role of germinal centers and IgV somatic hypermutation in lymphomagenesis.

Selected Publications

  • Dominguez-Sola, D., Ying, CY., Grandori, C., Ruggiero, L., Chen, B., Galloway, DA., Gu, W., Gautier, J., Dalla-Favera, R. Non-transcriptional control of DNA replication by c-myc. Nature 448:445-51, 2007.
  • Saito, M., Gao, J., Basso, K., Kitagawa,Y., Smith, PM., Pasqualucci, L., Dalla-Favera, R. A Signaling Pathway Mediating Downregulation of BCL6 in Germinal Center B Cells Is Blocked by BCL6 Gene Alterations in B Cell Lymphoma. Cancer Cell 12:280-292, 2007.
  • Klein, U., Dalla-Favera, R.. Germinal centres: role in B-cell physiology and malignancy. Nat Rev Immunol. 8:22-33, 2008.
  • Compagno, M., Lim, W.K., Grunn, A., Nandula, S.V., Brahmachary, M., Shen, Q., Bertoni, F., Ponzoni, M., Scandurra, M., Califano, A., Bhagat, G., Chadburn, A., Dalla-Favera, R. and Pasqualucci, L. Mutations of multiple genes cause deregulation of the NF-kB pathway in diffuse large B-cell lymphoma. Nature 459:717-21, 2009.
  • Klein, U., Lia, M., Crespo, M., Siegel, R., Shen, Q., Mo, T., Ambesi-Impiombato, A., Califano, A., Migliazza, A., Bhagat, G., Dalla-Favera, R. The DLEU2/miR-15a/16-1 cluster controls B-cell proliferation and its deletion leads to chronic lymphocytic leukemia. Cancer Cell (in Press)

Click here to view Dr. Dalla-Favera's profile.

Donna L. Farber, MD

Academic Title(s):

Professor of Surgical Sciences (in surgery)

Department(s)/Division(s):

Columbia Center for Translational Immunology

Contact Information:

Tel: (212) 305-6030
Email: df2396@columbia.edu

Research

Research in the laboratory is focused on immunological memory, and the role of memory T cells in anti-viral immunity, transplantation and autoimmunity. We are taking multiple in vivo, cellular, biochemical and molecular approaches to study the mechanisms by which memory CD4 T cells can be generated, how they persist and undergo homeostasis in vivo, and how they mediate protective immunity to respiratory pathogens such as influenza. In addition, we are studying how a memory T cell response can be modulated to optimize protective immunity to pathogens while minimizing deleterious consequences of memory T cells in transplantation and autoimmunity. We have recently identified that memory CD4 T cells exist as subsets that circulate through multiple tissue sites and also tissue-resident populations that are retained within non-lymphoid tissues such as the lung. These tissue-retentive memory T cells in the lung can mediate efficacious protection to repiratory pathogens. Our future research goals are to translate our findings from mouse models to further understand the basis of immune protection and immunoregulation in humans, with a focus on elucidating features of tissue-immunity in humans, to lead to improve therapies for infectious and autoimmune disease and more targeted regulation of the immune response in transplantation.

Selected Publications

  • Moulton, V., Bushar, N.D., Leeser, D., Patke, D.S. and Farber, D.L. (2006) Divergent generation of heterogeneous memory CD4 T cells. J. Immunol. 177: 869-876.
  • Moulton, V. and Farber, D.L. (2006) Committed to memory: lineage choices for T cells. Trends Immunol. 27: 261-67.
  • Ndejembi, M.P., Patke, D.S., Bingaman, A.W., Chandok, M.R., Azimzadeh, A., Nadler, S.G., and Farber, D.L. (2006) Control of Memory CD4 T cell recall by the CD28 costimulatory pathway. J. Immunol. 177: 7698-7706.
  • Zhang, X., Dong, H., Lin. W., Voss, S., Hinkley, L., Westergren, M., Berry, D., Lewellen, D., Vile, R. Chen, L., Farber, D.L., and Strome, S.E. (2006) Human Bone Marrow: a reservoir for enhanced effector-memory CD8 T Cells with potent recall function. J. Immunol. 177: 6730-6737.
  • Chandok, M.R., Okoye, F.I., Ndejembi, M.P. and Farber, D.L. (2007) A biochemical signature for rapid recall of memory CD4 T cells. J. Immunol. 179:3689-3698.
  • Okoye, F.I., Krishnan, S., Chandok, M.R., Tsokos, G.C., and Farber, D.L. (2007) Proximal Signaling control of human CD4 T cell function. Clin. Immunol. 125:5-15.
  • Tang, A.L., Njau, M.N., Teijaro, J.R., Azimzadeh, A., Nadler, S.G. and Farber, D.L. (2008) CTLA4 expression is an indicator and regulator of CD4+FoxP3+ T cell homeostasis. J.Immunol. 181:1806-1813.
  • Verhoeven, D., Teijaro, J.R., and Farber, D.L. (2008) Heterogeneous memory T cells in anti-viral immunity and immunopathology. Viral Immunology. 21:99-113.
  • Farber, D.L. (2009) Biochemical signaling pathways for memory T cell recall. Sem. Immunol. 21: 84-91.
  • Teijaro, J.R., Njau, M.P., Verhoeven, D., Chandran, S., Nadler, S.G., Hasday, J, and Farber, D.L. (2009) Costimulation modulation uncouples protection from immunopathology in memory T cell responses to influenza virus. J. Immunol. 182:6834-6843.
  • Verhoeven, D. and Farber, D.L. (2009) Rapid Communication: Pulse-oximetry accurately predicts lung pathology and the immune response during influenza infection. Virology. 390:151-156
  • Sener, A., Tang, A.L. and Farber, D.L. (2009) Memory T cell predominance following T cell depletional therapy derives from homeostatic expansion of naive T cells. Am. J. Transplant. 9:2615-2623.
  • Chandran, S., Verhoeven, D., Teijaro, J.R., Fenton, M. and Farber, D.L. (2009) TLR2 engagement on DC promotes high frequency effector and memory CD4 T cell responses. J. Immunol. 183:7832-41.
  • Bushar, N.D., Corbo, E., Schmidt, M., Maltzman, J.S. and Farber, D.L. (2010) Ablation of SLP-76 signaling after T cell priming generates memory CD4 T cells impaired in steady-state and cytokine-driven homeostasis. Proc. Nat'l. Acad. Sci. U.S.A. 107:827-831.
  • Teijaro, J.R., Verhoeven, D., Page, C.A. and Farber, D.L. (2010) Memory CD4 T cells Direct Protective Responses to Influenza Virus in the Lung through Helper-independent Mechanisms. J. Virol. 84:9217-26. (selected for editors' spotlight feature)

Click here to view Dr. Farber's profile.

Mady Hornig, MD

Academic Title(s):

Research Scientist

Department(s)/Division(s):

Center for Infection and Immunity, Mailman School of Public Health

Contact Information:

Tel: (212) 342-9036
Email: mady.hornig@columbia.edu

Research

Hornig's interest is in the role of microbial, immune, and toxic stimuli in the development of psychiatric illnesses. Her contributions include establishment of animal models of immune-mediated neurodevelopmental disorder pathogenesis (bornavirus, 1999; immunotoxins, 2004; PANDAS, 2004, 2010). Other recent projects include a study of immune and neuroendocrine factors in West Nile virus encephalitis in senescent mice. She also uses epidemiologic approaches to investigate the immunopathogenesis of neuropsychiatric disorders such as autism, schizophrenia, mood disorders, AD/HD, PANDAS and chronic fatigue syndrome (CFS). She will direct the Chronic Fatigue Initiative, to be based at CII, focusing on pathogen discovery and pathogenesis in CFS, and is a lead investigator for the Autism Birth Cohort (ABC), a prospective birth cohort study in Norway of 108,000 mothers, fathers, and their children that is identifying how genes and maturational factors interact with environmental agents to lead to autism. Proteomic analyses of umbilical cord samples, under Hornig's direction, are already identifying potential birth biomarkers for autism. She collaborates with Dr. Jill Goldstein (Harvard) on several projects involving other prospective birth cohorts, examining the influence of immune molecules on the prenatal development of sexually-dimorphic, emotional brain circuitry and function and their role in the genesis of schizophrenia, major depression, and cardiovascular disease in adults. Her work on the MIND (Microbiology and Immunology of Neuropsychiatric Disorders) Project, a large study of individuals with mood disorders and schizophrenia, addresses the potential role of Borna disease virus in the pathogenesis of these disorders. Using multiplexed immunoassay approaches, this project also seeks to define host immune and oxidative stress response profiles that could serve as proxies for exposure to known or hypothesized infectious and immune challenges, prior to the onset of illness.

Selected Publications

  • Hornig M, Mozley PD, Amsterdam JD. HMPAO SPECT brain imaging in treatment-resistant depression. Prog Neuro-Psychopharmacol Biol Psychiatry 1997;21:1097-1114
  • Hornig M, Goodman DBP, Kamoun M, Amsterdam JD. Positive and negative acute phase proteins in affective subtypes. J Affective Disord 1998;49:9-18
  • Hornig M, Amsterdam JD, Kamoun M, Goodman DBP. Autoantibody disturbances in affective disorders: a function of age and gender? J Affective Disord 1999;55:29-37
  • Hornig M, Weissenböck H, Horscroft N, Lipkin WI. An infection-based model of neurodevelopmental damage. Proc Natl Acad Sci USA 1999;96:12102-12107
  • Hoffman KL, Hornig M, Yaddanapudi K, Jabado O, Lipkin WI. A murine model for neuropsychiatric disorders associated with group A ?-hemolytic streptococcal infection. J Neurosci 2004;24:1780-1791
  • Hornig M, Chian D, Lipkin WI. Neurotoxic effects of postnatal thimerosal are mouse strain-dependent. Mol Psychiatry 2004;9:833-845
  • Hornig M, Briese T, Buie T, Bauman ML, Lauwers G, Siemetzki U, Hummel K, Rota PA, Bellini WJ, O'Leary JJ, Sheils O, Alden E, Pickering L, Lipkin WI. Lack of association between measles virus vaccine and autism with enteropathy: a case-control study. PLoS ONE 2008;3:e3140
  • De Miranda J, Yaddanapudi K, Hornig M, Lipkin WI. Astrocytes recognize intracellular polyinosinic-polycytidylic acid via MDA-5. FASEB J 2009;23:1064-1071
  • Yaddanapudi K, Hornig M, Serge R, De Miranda J, Baghban A, Villar G, Lipkin WI. Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS). Mol Psychiatry 2010;15:712-726
  • Palacios G, Hornig M, Cisterna D, Savji N, Bussetti AV, Kapoor V, Hui J, Tokarz R, Briese T, Baumeister E, Lipkin WI. Streptococcus pneumoniae coinfection is correlated with the severity of H1N1 pandemic influenza. PLoS ONE 2009;4:e8540
  • De Miranda J, Yaddanapudi K, Hornig M, Villar G, Serge R, Lipkin WI. Induction of Toll-Like Receptor 3-mediated immunity during gestation inhibits cortical neurogenesis and causes behavioral disturbances. MBio 2010;1:e00176-10

Click here to view Dr. Hornig's profile.

Ulf Klein, PhD

Academic Title(s):

Assistant Professor of Pathology & Cell Biology and Microbiology & Immunology in the Herbert Irving Comprehensive Cancer Center

Department(s)/Division(s):

Pathology & Cell Biology and Microbiology & Immunology

Contact Information:

Tel: (212) 851-5243
Email: uk30@columbia.edu

Research

Dr. Klein's laboratory's major research interests are focused on the elucidation of the molecular mechanisms that govern the differentiation of B cells within the germinal center (GC), the microenvironment that forms in the lymphoid tissues upon T-cell dependent activation of B cells to invading microorganisms. The GC is the place where high-affinity antibodies are generated by somatic hypermutation of the Ig variable region (IgV) genes of antigen-activated B cells, and where the B cell switches from IgM expression to other isotypes with different effector functions. Moreover, the GC microenvironment is the main source of antibody-secreting plasma cells and memory B cells that are able to mount a rapid and specific antibody response upon re-exposure of antigen. However, the beneficial role of GC B cells in immunity is somewhat counterbalanced by their detrimental role in lymphomagenesis, as it was found that the majority of lymphomas originate from GC B cells. Therefore, an equally important focus of the laboratory is to investigate whether and how the molecular mechanisms involved in normal GC B cell differentiation are disrupted in B-cell tumors. Since genomic lesions in B cells may cause deregulated expression of developmentally important transcription factors, thereby potentially abrogating the control of cellular processes including proliferation, apoptosis and differentiation, these studies are expected to provide insight into the transformation of the various types of mature B-cell lymphomas.

Selected Publications

  • Lia, M., A. Carette, H. Tang, Q. Shen, T. Mo, G. Bhagat, R. Dalla-Favera, and U. Klein. Functional dissection of the chromosome 13q14 tumor suppressor locus using transgenic mouse lines. Blood Dec 15, 2011 [Epub ahead of print]
  • Klein, U., M. Lia, M. Crespo, R. Siegel, Q. Shen., T. Mo, A. Ambesi-Impiombato, A. Migliazza, A. Califano, G. Bhagat, and R. Dalla-Favera. The DLEU2/mir-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia. Cancer Cell 17:28-40, 2010
  • Wang, K., M. Saito, B.C. Bisikirska, M.J. Alvarez, W.K. Lim, P. Raibhandari, Q. Shen, I. Nemenman, K. Basso, A.A. Margolin, U. Klein, R. Dalla-Favera, and A. Califano. Genome-wide identification of post-translational modulators of transcription factor activity in human B cells. Nat. Biotechnol. 27:829-839, 2009
  • Zheng, Y., A. Chaudhry, A. Kas, P. deRoos, J.M. Kim, T.-T. Chu, L. Corcoran, P. Treuting, U. Klein, and A.Y. Rudensky. Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control Th2 responses. Nature 458:351-356, 2009
  • Klein, U., and R. Dalla-Favera. Germinal centres: role in B cell physiology and malignancy. Nat. Rev. Immunol. 8:22-33, 2008
  • Klein, U., S. Casola, G. Cattoretti, Q. Shen, M. Lia, T. Mo, T. Ludwig, K. Rajewsky, and R. Dalla-Favera. Transcription factor IRF4 controls plasma cell differentiation and class-switch recombination. Nat. Immunol. 7:773-782, 2006

Click here to view Dr. Klein's profile.

Matthew Perzanowski, PhD

Academic Title(s):

Associate Professor

Department(s)/Division(s):

EHS

Contact Information:

Tel: (212) 305-3465
Email: mp2217@columbia.edu

Research

Dr. Perzanowski is a co-investigator on several established prospective cohort studies. His current research at MSPH is exploring paradigms of exposures related to asthma in an area of the world with one of the highest prevalence of asthma, inner-city NYC. He is the principal investigator on the NIH (NIEHS) funded R01, NYC Neighborhood Asthma and Allergy Study which will examine neighborhood differences in asthma prevalence to better understand the great difference in asthma risk between children living just city blocks apart. Two other major research goals are implementing non-invasive measurements of airway inflammation in pediatric population studies and evaluating the influence of the 'hygiene hypothesis' on inner-city asthma.

Selected Publications

  • Perzanowski MS, Miller RL, Tang D, Ali DB, Garfinkel RS, Chew GL, Goldstein IF, Perera FP, Barr RG "Prenatal acetaminophen exposure and risk of wheeze at age 5 years in an urban, low-income cohort." Thorax in press.
  • Perzanowski MS, Platts-Mills, TAE "Further confirmation of the relevance of cockroach and dust mite sensitization to inner-city asthma morbidity" Clin Exp Allergy 39 1291-3 2009.
  • Perzanowski MS, Chew GL, Divjan A, Johnson A, Panjwani K, Sheares BJ, Goldstein IF, Garfinkel RS, Platts-Mills TA, Perera FP, Miller RL "Cat ownership is a risk factor for developing anti-cat IgE but not wheeze at age 5 in a low income urban NYC cohort" J Allergy Clin Immunol 121 1047-52 2008.
  • Perzanowski MS, Canfield SM, Chew GL, Mellins RB, Hoepner LA, Jacobson JS, Goldstein IF "Birth order, atopy, and symptoms of allergy and asthma among inner-city children attending Head Start in New York City." Clin Exp Allergy 38 968-76, 2008.
  • Perzanowski MS, Chew CG, Aalberse R, de Blay F "Allergic Asthma" Public Health Significance of Urban Pests Ed. Bonnefoy, Kampen, Sweeney World Health Organization Copenhagen/Denmark 7-52 2008.
  • Perzanowski MS, Miller RL, Thorne PS, Barr RG, Divjan A, Sheares BJ, Garfinkel RS, Goldstein IF, Perera FP, Chew GL "Endotoxin inner-city homes and the association with atopy and wheeze in the first two years of life." J Allergy Clin Immunology 117 1092-9 2006.

Click here to view Dr. Perzanowski's profile.

Jai Radhakrishnan, MD

Academic Title(s):

Assoc Professor of Clinical Medicine

Department(s)/Division(s):

Medicine

Contact Information:

Tel: (212) 305-5020
Email: jr55@columbia.edu

Research

Dr. Radhakrishnan studies Lupus Nephritis. It is unclear whether the primarily T cell infiltrate in lupus nephritis is a primary process or simply a secondary reactive process to another type of injury (5) and further characterization of the phenotype of the infiltrating cells would be useful. Interestingly, in a murine model of SCID with adriamycin nephrosis (AN), a model for interstitial inflammation, reconsitution of the mice with CD4+CD25+ cells significiantly reduced glomerulosclerosis and tubular injury as compared to unreconstituted mice (4), which has both mechanisitic and therapeutic implications for lupus nephritis. Therefore, his group proposed to examine the expression of FoxP3 in renal biopsies from SLE patients and see if higher levels of FoxP3 are protective against worsening interstitial inflammation and worsening renal function.

Selected Publications

  • Mycophenolate mofetil and intravenous cyclophosphamide are similar as induction therapy for class V lupus nephritis. Radhakrishnan J, Moutzouris DA, Ginzler EM, Solomons N, Siempos II, Appel GB. Kidney Int. 2009 Nov 4.
  • Nephrology image. Back-bench split of a deceased-donor horseshoe kidney for two transplant recipients. Guarrera JV, Arrington B, Birkhoff JD, Goldstein MJ, Ratner LE, Kelly JA, Radhakrishnan J, Hardy MA. Kidney Int. 2009 Nov;76(9):1012.
  • Polycystic liver disease treated with therapeutic excision. Das KK, Samstein B, Guarrera JV, Kinkhabwala M, Ratner LE, Radhakrishnan J. Kidney Int. 2009 Oct;76(7):803.
  • Renal biopsy in the very elderly. Moutzouris DA, Herlitz L, Appel GB, Markowitz GS, Freudenthal B, Radhakrishnan J, D'Agati VD. Clin J Am Soc Nephrol. 2009 Jun;4(6):1073-82. Worth a second look. Goldberg D, Weisberg I, Diuguid D, Gaglio P, Alobeid B, Fink S, Radhakrishnan J. Am J Med. 2009 Jan;122(1):24-6.
  • Oxalate nephropathy complicating Roux-en-Y Gastric Bypass: an underrecognized cause of irreversible renal failure. Nasr SH, D'Agati VD, Said SM, Stokes MB, Largoza MV, Radhakrishnan J, Markowitz GS. Clin J Am Soc Nephrol. 2008 Nov;3(6):1676-83.
  • The case/Renal failure after percutaneous closure of a perivalvular leak. Labban B, Radhakrishnan J.Kidney Int. 2008 Aug;74(4):539-40.
  • A case of nephrocalcinosis.Herlitz LC, Bruno R, Radhakrishnan J, Markowitz GS. Kidney Int. 2009 Apr;75(8):856-9.
  • A 56-year-old woman with sarcoidosis and acute renal failure. Dahl K, Canetta PA, D'Agati VD, Radhakrishnan J. Kidney Int. 2008 Sep;74(6):817-21.
  • Transjugular intrahepatic portosystemic shunts in hemodialysis-dependent patients and patients with advanced renal insufficiency: safety, caution, and encephalopathy. Haskal ZJ, Radhakrishnan J. J Vasc Interv Radiol. 2008 Apr;19(4):516-20.
  • Towards the incidence of acute phosphate nephropathy. Markowitz GS, Radhakrishnan J, D'Agati VD. J Am Soc Nephrol. 2007 Dec;18(12):3020-2.
  • Rituximab treatment of dysproteinemias affecting the kidney: a review of three cases. Bhat P, Weiss S, Appel GB, Radhakrishnan J. Am J Kidney Dis. 2007 Oct;50(4):641-4.
  • Mycophenolate mofetil for the treatment of interstitial nephritis. Preddie DC, Markowitz GS, Radhakrishnan J, Nickolas TL, D'Agati VD, Schwimmer JA, Gardenswartz M, Rosen R, Appel GB. Clin J Am Soc Nephrol. 2006 Jul;1(4):718-22.
  • Cardiac transplantation using extended-donor criteria organs for systemic amyloidosis complicated by heart failure. Maurer MS, Raina A, Hesdorffer C, Bijou R, Colombo P, Deng M, Drusin R, Haythe J, Horn E, Lee SH, Marboe C, Naka Y, Schulman L, Scully B, Shapiro P, Prager K, Radhakrishnan J, Restaino S, Mancini D. Transplantation. 2007 Mar 15;83(5):539-45.
  • The burden of prescription coverage of kidney failure patients in the United States: is Medicare Part D the answer? Radhakrishnan J. Kidney Int. 2006 Apr;69(7):1099-100.

Click here to view Dr. Radhakrishnan's profile.

Boris Reizis, PhD

Academic Title(s):

Associate Professor

Department(s)/Division(s):

Dept. of Microbiology and Immunology

Contact Information:

Tel: (212) 305-5793
Email: bvr2101@columbia.edu

Research

The Reizis lab studies the development, regulation and function of innate immune cell types, including classical dendritic cells and interferon-producing plasmacytoid dendritic cells.

Selected Publications

  • Sathaliyawala, T., O'Gorman, W.E., Greter, M., Bogunovic, M., Konjufca, V., Hou, Z.E., Nolan, G.P., Miller, M.J., Merad, M. and Reizis B. (2010) Mammalian target of rapamycin controls dendritic cell development downstream of Flt3 ligand signaling, Immunity 33: 597–606.
  • Arenzana, T.L., Smith-Raska, M.R. and Reizis, B. (2009) Transcription factor Zfx controls BCR-induced proliferation and survival of B lymphocytes. Blood 113: 5857-5867.
  • Birnberg, T., Bar-On, L., Sapoznikov, A., Caton, M.L., Cervantes-Barragán, L., Makia, D., Krauthgamer, R., Brenner, O., Ludewig, B., Brockschnieder, D., Riethmacher, D., Reizis, B.* and Jung, S*. (2008) Lack of conventional dendritic cells is compatible with normal development and T cell homeostasis, but causes myeloid proliferative syndrome. Immunity 29: 986-997. (*corresponding authors)
  • Cisse, B., Caton, M.L., Lehner, M., Maeda, T., Scheu, S., Locksley, R., Holmberg, D., Zweier, C., den Hollander, N.S., Kant, S.G., Holter, W., Rauch, A., Zhuang, Y. and Reizis B. (2008) Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell 135: 37-48.
  • Hou, B., Reizis, B. and DeFranco, A.L. (2008) Toll-like receptor-mediated dendritic cell-dependent and -independent stimulation of innate and adaptive immunity. Immunity 29: 272-82.
  • Travis, M.A., Reizis, B., Melton, A.C., Masteller, E., Tang, Q., Proctor, J.M., Wang, Y., Bernstein, X., Huang, X., Reichardt, L.F., Bluestone, J.A. and Sheppard, D. (2007) Loss of integrin alpha(v)beta(8) on dendritic cells causes autoimmunity and colitis in mice. Nature 449: 361-365.
  • Caton, M.L., Smith-Raska, M.R. and Reizis, B. (2007) Notch-RBP-J signaling controls the homeostasis of CD8- dendritic cells in the spleen. J. Exp. Med. 204: 1653-1664. http://www.microbiology.columbia.edu/faculty/pdf/Realetal2008.pdf
  • Galan-Caridad, J.M., Harel, S., Arenzana, T.L., Hou, Z.E., Doetsch, F.K., Mirny, L.A. and Reizis, B. (2007) Zfx controls the self-renewal of embryonic and hematopoietic stem cells. Cell 129: 345-357.
  • Babbe, H., Chester, N., Leder, P. and Reizis, B. (2007) The Bloom's syndrome helicase is critical for development and function of the abT cell lineage. Mol. Cell. Biol. 27: 1947-1959.

Click here to view Dr. Reizis's profile.

Megan Sykes, MD

Academic Title(s):

Michael J. Friedlander Professor of Medicine and Professor of Microbiology & Immunology and Surgical Sciences (in Surgery)
Director, Columbia Center for Translational Immunology, Columbia University College of Physicians and Surgeons
Director of Research, Transplant Initiative, NewYork-Presbyterian Hospital
Director, Bone Marrow Transplantation Research, Division of Hematology/Oncology

Contact Information:

Tel: (212) 304-5696
Email: megan.sykes@columbia.edu

Research

Our research is in the areas of hematopoietic cell transplantation, achievement of graft-versus-leukemia effects without GVHD, organ allograft tolerance induction and xenotransplantation. My research program aims to utilize bone marrow transplantation as immunotherapy to achieve graft-versus-tumor effects while avoiding the common complication of such transplants, graft-versus-host disease. Our laboratory studies in this area have led to novel approaches that have been evaluated in clinical trials. Another major area has been to utilize bone marrow transplantation for the induction of transplantation tolerance, both to organs from the same species (allografts) and from other species (xenografts). Our laboratory has worked toward the development of clinically feasible, non-toxic methods of re-educating the T cell, B cell and NK cell components of the immune system to accept allografts and xenografts without requiring long-term immunosuppressive therapy. Our work has also extended into the area of xenogeneic thymic transplantation as an approach to tolerance induction, and into the mechanisms by which non-myeloablative induction of mixed chimerism reverses the autoimmunity of Type 1 diabetes.

Selected Publications

  • Zhao Y, Swenson K, Sergio JJ, Arn JS, Sachs DH, Sykes M. Skin graft tolerance across a discordant xenogeneic barrier. Nat. Med. 1996:2(11):1211-1216.
  • Sykes M, Szot GL, Swenson KA, Pearson DA. Induction of high levels of allogeneic hematopoietic reconstitution and donor-specific tolerance without myelosuppressive conditioning. Nat. Med. 1997;3:783-787. Wekerle T, Sayegh MH, Hill J, Zhao Y, Chandraker A, Swenson KG, Zhao G, Sykes M. Extrathymic T cell deletion and allogeneic stem cell engraftment induced with costimulatory blockade is followed by central T cell tolerance. J. Exp. Med. 1998;187:2037-2044.
  • Ohdan H, Yang Y-G, Shimizu A, Swenson KG, Sykes M. Mixed chimerism induced without lethal conditioning prevents T cell- and anti-Gal?1,3Gal-mediated graft rejection. J. Clin. Invest. 1999;104:281-290.
  • Fudaba Y, Spitzer TR, Shaffer JM, Kawai T, Fehr T, Delmonico FL, Preffer FI, Tolkoff-Rubin, Dey BR, Saidman SL, Kraus A, Bonnefoix T, McAfee S, Power K, Kattelman K, Colvin RB, Sachs DH, Cosimi AB Sykes M. Myeloma responses and tolerance following combined kidney and non-myeloablative marrow transplantation in vivo and in vitro analyses. Am. J. Transplant. 2006;6:2121-2133.
  • Chakraverty R, Cote D, Buchli J, Cotter P, Hsu R, Zhao G, Sachs T, Pitsilldes C, Bronson R, Means T, Lin C, Sykes M. An inflammatory checkpoint regulates recruitment of graft-versus-host reactive T cells to peripheral tissues. J. Exp. Med. 2006;203(8):2021-2031.
  • Kawai T, Cosimi AB, Spitzer TR, Tolkoff-Rubin N, Suthanthiran M, Saidman S, Shaffer J, Preffer F, Ding R, Sharma V, Fishman J, Dey BR, Ko D, Hertl M, Goes N, Wong W, Williams W, Colvin RB, Sykes M, and Sachs DH. HLA-mismatched renal transplantation without maintenance immunosupression. New Engl. J. Med. 2008; 358(4): 353-361. PMCID: 18216355
  • Fehr T, Lucas C, Kurtz J, Onoe T, Zhao G, Hogan T, Vallot C, Rao A and Sykes M. A CD8 T cell-intrinsic role for the calcineurin-NFAT pathway for tolerance induction in vivo. Blood 2010; 115: 1280-1287. PMCID: PMC2826238
  • Onoe T, Kalscheuer H, Chittenden M, Zhao G, Yang YG, Sykes M. Homeostatic expansion and phenotypic conversion of human T cells depend on peripheral interactions with APCs. J Immunol. 2010 Jun 15;184(12):6756-65. PMID: 20483739
  • Saito TI, Li H, Sykes M. Invariant natural killer T cells are required for antitumor responses induced by host-versus-graft responses. J. Immunol. 2010. Aug 15;185(4):2099-105. PMID: 20631307

Click here to view Dr. Sykes's profile.

Timothy C. Wang, MD

Academic Title(s):

Silberberg Professor of Medicine

Department(s)/Division(s):

Medicine/ Division of Digestive and Liver Disease

Contact Information:

Tel: (212) 851-4581
Email: tcw21@columbia.edu

Research

Dr. Wang's main interest is in the role of inflammation and stem cells in carcinogenesis. He established Helicobacter- mouse models of gastric cancer and was the first to report a role for bone marrow-derived stem cells in gastric cancer. His laboratory has also identified markers for human gastric cancer stem cells, and showed that overexpression of a single cytokine (IL-1beta) was sufficient to induced gastric tumorigenesis. This year he has reported on novel markers (Cck2r) for colonic stem cells. As the leader of the Columbia University Tumor Microenvironment Network, he has recently investigated the importance of the stem cell niche in governing stem cell differentiation, and how this niche is altered in chronic inflammatory states that predispose to cancer. He is currently investigating the role of both fibroblasts and myeloid cells in carcinogenesis. Dr. Wang is a recipient of the AGA Funderberg Gastric Cancer Award, a member of ASCI and AAP, and is the Editor of the first textbook on gastric cancer, “The Biology of Gastric Cancer” (Springer 2008). He is Associate Editor for Gastroenterology and Editor in Chief of Therapeutic Advances in Gastroenterology. He is the author of more than 160 peer-reviewed publications.

Click here to view Dr. Wang's profile.