Six Columbia Scientists Awarded NIH High-Risk, High-Reward Grants

Six Columbia University scientists have received NIH High-Risk, High-Reward grants that are given to exceptionally creative scientists proposing unconventional, but potentially high-impact, research that addresses major challenges in medicine.

The High-Risk, High-Reward Research program supports highly innovative research proposals that, due to their inherent risk, may struggle in the traditional peer-review process despite their transformative potential. This year, 106 projects were funded.

Rui Costa, PhD

Costa was one of 10 scientists this year to receive a Pioneer Award, awarded to scientists with outstanding records of creativity who are pursuing new research directions.

With the award, Costa will explore the oft-neglected ways in which the brain might influence the rest of the body and impact health. When planning to pick an apple, for example, the brain triggers muscle activity but also an expectation of food that results in the release of insulin from the pancreas.

Costa will use his Pioneer Award to explore the neural circuitry governing the control of internal organs, focusing on insulin release and suppression of the immune system by the spleen. The findings may impact health in unexpected ways: Mental disorders such as anxiety and depression may emerge from these interactions between the brain and other internal organs.

Costa is professor of neuroscience and neurology at Columbia University Vagelos College of Physicians and Surgeons and director and CEO of Columbia’s Zuckerman Institute. Read more about his research on the Zuckerman website.

Hemali Phatnani, PhD, and Ai Yamamoto, PhD

Phatnani and Yamamoto belong to one of 19 individuals or teams to receive a Transformative Research Award, which promotes unconventional projects with the potential to create new paradigms or overturn existing ones. 

The researchers' project focuses on amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. Unlike most ALS researchers who look for genetic mutations to reveal how the disease arises, the Phatnani and Yamamoto team will explore whether physical changes within cells caused by molecular overcrowding may underlie the disorder. If so, the research would alter the view of ALS pathogenesis and provide a new framework to find better therapies for the disease.

The five-year project is a collaboration of the Phatnani and Yamamoto labs at Columbia; Liam Holt, PhD, at New York University; Jenna Gregory, PhD, at the University of Edinburgh; and the New York Genome Center, where Phatnani is a core faculty member and director of the Center for Genomics of Neurodegenerative Disease. At VP&S, Phatnani is assistant professor of neurological sciences (in neurology), and Yamamoto is associate professor of neurology and of pathology & cell biology.

Mijo Simunovic, PhD

With recent advancements in stem cell biology, it has become possible to create 3D tissues—organoids—that resemble human organs and perform some of their functions. But human organoids do not develop as organs do and are still far away from acting as complete organs.

Mijo Simunovic, PhD, who received a New Innovator Award, aims to develop a stem cell-based system that more accurately mimics natural organ development and will have the capacity to generate highly precise human tissues. In creating this system, Simunovic will break away from current paradigms used to create human organoids—which rely on the self-organizing ability of stem cells—and instead combine tissue engineering and gene editing to precisely instruct cells what to do and where to go during in vitro organ development. The research may make the possibility of lab-grown replacement organs a reality one day, as well as provide researchers with more realistic in vitro models of disease.

Simunovic is assistant professor in the Departments of Chemical Engineering and Genetics & Development and a member of the Columbia Stem Cell Initiative; the lab is located on the CUIMC campus.

Nikhil Sharma, PhD

Sharma received a New Innovator Award to better understand the molecular and cellular mechanisms that underlie the perception of pain.

The perception of pain is caused by intense or damaging stimuli, such as extremes in temperature or force. Though significant effort is made to understand how the brain generates the perception of pain, comparatively little is known about how painful stimuli are initially detected by neurons in skin and other organs. Sharma has previously identified many previously unknown pain-detecting neurons and in this project will further analyze them to understand the structure and function of each.

The results may lead to the development of new pain therapeutics that do not target neural circuits in the brain and may have less potential for abuse.

Sharma is assistant professor of molecular pharmacology & therapeutics at VP&S.

Anne Nigra, PhD

Nigra, a postdoctoral research scientist in the Department of Environmental Health Sciences of the Mailman School of Public Health, is one of 13 scientists who received an Early Independence Award, which gives exceptional junior scientists the opportunity to move immediately into independent research positions.

Her project will evaluate the contribution of racial, ethnic, and socioeconomic inequalities in public drinking water contaminant exposures to disparities in birth outcomes across the United States. As a part of her work, Nigra is developing a novel database of exposure estimates of regulated contaminants in public water systems across the entire United States at multiple spatial resolutions. The database will enable nationwide epidemiologic studies linking public water exposures to numerous related outcomes.