Three CUMC Scientists Awarded Grants for
“Out-of-the-Box” Research

David Fidock thinks he has found a way to cure malaria. Naa Oyo Kwate believes a “counter marketing” campaign may improve African Americans’ health by reducing the stress caused by racism. And Alla Grishok has an unconventional explanation for what thousands of short interfering RNAs are doing in our cells.

All three CUMC researchers have received NIH Director’s High-Risk Research Awards to pursue ideas that have potential to make a major impact on important problems in biomedical and behavioral research.

The awards were created by the NIH to support scientists who have “out-of-the-box” ideas that have the potential for high rewards but may be too novel or span a too diverse range of disciplines to fare well in the traditional peer review process. Awards are granted under three programs: Transformative R01 Awards, for projects that have the potential to transform a field of science; Pioneer Awards, for research ideas substantially different from those already being pursued; and New Innovator Awards, for early-stage investigators.

This year’s CUMC awardees are

Dr. Fidock proposes an entirely novel approach to developing vaccines and drugs to prevent malaria, which is starting to develop resistance to first-line artemisinin treatments. The project is based on his recent discovery of the way malaria parasites acquire fatty acids while replicating in the liver. Exploiting the dependency of fatty acid synthesis by liver stage parasites, his laboratory will develop fatty acid synthesis-deficient, genetically attenuated parasite vaccines that arrest in the liver, causing a host immune response that protects against infectious challenge. In addition, Dr. Fidock will target parasite synthesis, as well as salvage host fatty acids, as a means to develop novel prophylactic and curative medicines.

Naa Oyo Kwate, PhD
Assistant professor of sociomedical sciences
Mailman School of Public Health
New Innovator Award: Immunologic Effects and a Structural “Counter Marketing” Intervention: Racism, the HPA Axis, and African American Health

Significant disparities in major chronic illnesses, including cardiovascular disease, cancer, and overweight/obesity, continue to describe the current picture of health for African Americans. Dr. Kwate will examine how experiences with racism, a significant stressor in the lives of African Americans, activate the hypothalamic-pituitary-adrenocortical axis and negatively affect health. Her research will enroll African Americans from New York City in two longitudinal investigations. The first is an investigation of how racism affects immune and metabolic function and overall physical health, psychological well being, and health behaviors. The second study will deploy a “counter marketing” campaign at a neighborhood level to minimize the likelihood of internalized racism. Taken together, the studies attempt to answer two critical unanswered questions in biomedical and behavioral research: 1) How does racism get into the body? and 2) What do we do about it?

Alla Grishok, PhD
Assistant professor of biochemistry & molecular biophysics
College of Physicians & Surgeons
New Innovator Award: Investigating the Potential of Endogenous RNAi in Mediating Adaptation to Environment

RNA interference (RNAi) provides defense against exogenous nucleic acids, such as viruses and transposons, in diverse organisms. The production of short interfering RNAs (siRNAs) antisense to the viral or transposon sequences is a hallmark of the RNAi response. The discovery of the endogenous siRNAs (endo-siRNAs) matching thousands of protein-coding sequences in animalsposes a question about their function. Dr. Grishok’s recent work has revealed that RNAi in C. elegans appears beneficial for stress resistance and lifespan extension. She hypothesizes that RNAi in C. elegans is subject to natural selection and that the environment can alter the composition of siRNAs to achieve maximum fitness. If true, such RNAi-based mechanisms may be involved in the immune escape and drug resistance of malignant tumors and in other cases when cells evolve to escape the action of therapeutic agents.

In previous years, two scientists now at Columbia University Medical Center have been awarded Pioneer Awards.

With help from a 2004 Pioneer Award, Larry Abbott, PhD, the William Bloor Professor of Theoretical Neuroscience and professor of physiology & cellular biophysics (in biological sciences), has developed new mathematical models of brain function that merge two areas of research: how external stimuli drive perception and how internal processing influences behavior. The models pave the way for future research on the science of decision-making and other aspects of human perception and behavior that are poorly understood.

Tom Maniatis, PhD, incoming chair of the Department of Biochemistry & Molecular Biophysics, uses his 2008 Pioneer Award to explore the underlying mechanisms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease of motor neurons, by characterizing cultured motor neurons from patient-derived stem cells. An understanding of ALS disease mechanisms could lead to the development of a therapy for this incurable disease.

More information on NIH Director’s High-Risk Research Awards is at http://www.nihroadmap.nih.gov/highrisk/.