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NIH Awards ‘High-Risk, High-Reward’ Grants to Seven UCSF Researchers

Grants Are Reserved for Most Creative Approaches to Major Biomedical Challenges

By Pete Farley | UCSF.edu | October 6, 2015

The National Institutes of Health (NIH) has awarded seven grants to UC San Francisco scientists to pursue innovative approaches to major contemporary challenges in biomedical research. The highly competitive grants, which were announced today among 78 such awards nationwide, were made under the High-Risk, High-Reward Research program supported by the NIH Common Fund.

“This program has consistently produced research that revolutionized scientific fields by giving investigators the freedom to take risks and explore potentially pioneering concepts,” said NIH Director Francis S. Collins, MD, PhD. “We look forward to the remarkable advances in biomedical research the 2015 awardees will make.”

For his innovative research on tuberculosis (TB), Jeffrey S. Cox, PhD, received the NIH’s Pioneer Award, intended for investigators at all career levels to pursue new research directions and develop groundbreaking approaches with a high impact on a broad area of biomedical or behavioral science. Cox, professor of microbiology and immunology, uses genome sequencing, bioinformatics, advanced imaging techniques, animal models of infection, and high-throughput assays to study how Mycobacterium tuberculosis (Mtb), the causative agent of TB, evades immune system defenses. Mtb infects two billion people worldwide, and drug-resistant TB is a rapidly growing public health problem.

Four UCSF researchers received the New Innovator Award, which supports unusually innovative research from early career investigators who are within 10 years of their doctoral degree or clinical residency and have not yet received a research project grant (R01) or equivalent NIH grant.

  • Sophie Dumont, PhD, studies how chemical processes and mechanical forces interact within cells, at scales ranging from the molecular level to the tissue level. In particular, Dumont and colleagues are interested in how cells equally distribute genetic material when cells divide, a process with consequences for health, since errors in chromosome segregation can lead to birth defects and disease. Dumont is assistant professor of cell and tissue biology and of cellular and molecular pharmacology, as well as a member of the Helen Diller Family Comprehensive Cancer Center.
     
  • Karunesh Ganguly, MD, PhD, an assistant professor of neurology, does both basic and translational research on strategies to enhance recovery of the nervous system after injury or stroke. With UCSF collaborators, Ganguly is exploring how a deeper understanding of neural recovery can lead to better design and implementation of neuroprosthetic devices. These “brain-machine interfaces,” which translate brain signals into motor commands, promise to enable patients paralyzed by stroke or injury to regain control of affected limbs.
     
  • Martin Kampmann, PhD, assistant professor of biochemistry and biophysics and a member of UCSF’s Institute for Neurodegenerative Diseases, studies the “proteostasis network,” the process by which cells maintain their proteins in a functional and balanced state. As cells are challenged and “rewired” in disease, especially cancer and neurodegenerative diseases such as Alzheimer’s disease, cells must dynamically adjust, clearing out pathogenic proteins while continuing to function. By studying how proteostasis is disrupted, Kampmann aims to identify new drug targets.
     
  • Zachary A. Knight, PhD, assistant professor of physiology, studies the brain circuits that control feeding behavior. In research using brain-recording techniques developed just in the past few years, Knight and members of his lab have shown that the dominant model of how the brain’s “hunger circuit” works may be incorrect, which has ramifications for the development of anti-obesity therapies. Because this circuit is embedded within other complex brain circuits, Knight and his team are developing new tools to disentangle the distinctive anatomical and functional characteristics of the hunger circuit.

Two young UCSF scientists received NIH’s Early Independence Award, which provides an opportunity for exceptional junior scientists who have recently received their doctoral degree or finished medical residency to skip traditional post-doctoral training and move immediately into independent research positions.

  • Joseph Bondy-Denomy, PhD, a UCSF Sandler Fellow who recently moved to UCSF from the University of Toronto, received an Early Independence Award to support his research on the CRISPR/Cas9 system that bacteria use to protect themselves from viral infections. CRISPR/Cas9 has been much in the news as a tool that can edit the genomes of virtually any organisms, but Bondy-Denomy is interested in CRISPR/Cas9’s “original” role in bacterial immunity. Bondy-Denomy’s research has broad applications in understanding how microbes cause disease, and could lead to novel drug targets in the fight against antibiotic-resistant pathogens.
     
  • David A. Solomon, MD, PhD, a clinical fellow in the Department of Pathology, uses genomic approaches to advance precision cancer medicine. A member of UCSF’s Helen Diller Family Comprehensive Cancer Center, Solomon and collaborators have shown that mutations that disrupt the function of a gene known as STAG2 are present in many cancer types, and that STAG2 mutations may predict outcomes. In bladder cancer, for example, Solomon has shown that tumors with STAG2 mutations are less aggressive and less likely to recur after treatment. In a cancer known as Ewing’s sarcoma, however, STAG2 mutations are associated with more advanced disease and decreased survival. In both cases, STAG2 analyses can guide physicians’ treatment decisions and may spare patients from unnecessary tests.

This year, NIH awarded 13 Pioneer awards, 41 New Innovator awards, eight Transformative Research awards, and 16 Early Independence awards. The total funding, which represents contributions from the NIH Common Fund and multiple NIH institutes, centers, and offices, is approximately $121 million.

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