Six UCSF Scientists Awarded NIH Grants for High-Risk, High-Reward Research

The National Institutes of Health (NIH) has awarded six NIH Director’s Awards to early-career UC San Francisco scientists – a record number for the University. Recipients of the highly competitive grants were announced Oct. 2 among the 89 awards funded this year by the High-Risk, High-Reward Research program, part of the NIH Common Fund.

“This program supports exceptionally innovative researchers who have the potential to transform the biomedical field,” said NIH Director Francis S. Collins, MD, PhD. “I am confident this new cohort will revolutionize our approaches to biomedical research through their groundbreaking work.”

For her research on oxygen metabolism, Isha Jain, PhD, a Sandler Fellow and member of the Department of Physiology, received an NIH Director’s Early Independence Award. Established in 2011, these awards offer exceptional junior scientists who recently received their doctorates the opportunity to skip traditional postdoctoral training and move directly into independent research positions.

Jain takes a systems-level approach, focusing on how the body senses and responds to changes in oxygen levels. With her new award, she will conduct studies to elucidate why certain tissues, such as skeletal muscle, can survive under low oxygen conditions while others, notably brain tissue, are prone to damage when deprived of oxygen. Jain’s research may eventually lead to new treatments for stroke, heart attack and respiratory ailments characterized by prolonged deprivation of oxygen and nutrients that can cause severe tissue damage.

Five UCSF researchers received NIH Director’s New Innovator Awards. Established in 2007, these awards support early-career investigators whose work the NIH deems “unusually innovative.” Awardees must have completed their terminal degree or clinical residency no more than 10 years prior and cannot have received a research project grant or equivalent NIH grant.

Evan Feinberg, PhD, studies how the brain transforms sensory input into behavioral output. By developing tools that allow him to selectively manipulate specific connections, the sites of neuronal communication, Feinberg’s study will help explain how individual synapses contribute to information processing in the brain. Synaptic deficits are implicated in a variety of neurological disorders, from schizophrenia to epilepsy, and these tools and the discoveries they enable may eventually translate into new treatments for these diseases. Feinberg is a member of the UCSF Weill Institute for Neurosciences, the Department of Anatomy, the Kavli Institute for Fundamental Neuroscience and the Center for Integrative Neuroscience.

Stephen Floor, PhD, explores how RNA molecules in cells mediate gene expression and protein production. Floor employs novel methods that allow him to probe the behavior of individual RNA molecules, an approach that yields critical information about how each RNA contributes to cellular function. Floor’s efforts represent a significant advance over high-throughput sequencing and will provide a far more detailed picture of how individual RNA molecules behave and contribute to the proper functioning of cells, and how diseases like cancer emerge when RNA-mediated processes go awry. Floor’s research may also help improve emerging therapies in which RNA is injected directly into patients to target specific cells and mount a controlled response to repair cellular damage and fight disease. Floor is a member of the Department of Cell and Tissue Biology in the UCSF School of Dentistry and of the UCSF Helen Diller Family Comprehensive Cancer Center.

Luke Gilbert, PhD, uses synthetic biology to understand how genomes are regulated and how genes interact in normal and cancerous cells. Gilbert employs novel CRISPR-based tools in which the gene-editing portions of the CRISPR system have been adapted to allow researchers to target specific genes for activation or inactivation without altering the underlying DNA sequence. Using these tools to perturb gene activity, Gilbert is developing a genetic interaction map for the cell’s nucleus. The map will explore how 10 million pairs of genes function in concert while also illuminating the roles of genes that are poorly understood. Genetic interaction maps will allow researchers to identify “synthetic lethal” gene pairs – combinations of genes whose joint function is required for cell survival – and to potentially target these pairs to treat leukemia, lung and prostate cancers. Gilbert is member of the Department of Urology, Helen Diller Family Comprehensive Cancer Center and the joint UC Berkeley-UCSF Innovative Genomics Institute.

Kole Roybal, PhD, is exploring the therapeutic potential of synthetic immunology. Roybal is engineering novel disease-detecting and disease-response machinery into immune cells to create new cell-based therapies that could target and treat a variety of diseases. His approach involves fabricating new immune cell signaling proteins and customizing them so that they’re able to detect and respond to specific disease microenvironments, including those seen in cancer, autoimmunity and degenerative diseases. His efforts may soon lead to new therapies for cancer and autoimmune disorders. Roybal, an inaugural Chan Zuckerberg Biohub investigator, is a member of UCSF’s Department of Microbiology & Immunology, ImmunoX, the Parker Institute for Cancer Immunotherapy and the UCSF Helen Diller Family Comprehensive Cancer Center.

Tiffany Scharschmidt, MD, is elucidating the mechanisms that underlie the complex dialog between the skin’s microbiome and the immune system. Skin is among the most microbially and immunologically rich sites on the body, with more than a million bacterial and immune cells occupying every square centimeter of its surface. Early in life, the immune system learns to distinguish “good” commensal microbes from pernicious pathogens. Scharschmidt is trying to understand how this occurs by exploring the ways the immune system and the skin’s commensal bacteria communicate with each other. Understanding how the immune system privileges beneficial microbes over problematic ones may lead to better therapies for inflammatory skin diseases while also contributing to a deeper understanding of the fundamental mechanisms underlying adaptive immunity. Scharschmidt is a member of the Department of Dermatology, ImmunoX and the Program in Microbial Pathogenesis & Host Defense.

“The future of science and our hopes for the advancement of human health lie in the hands of our youngest, most pathbreaking researchers,” said UCSF’s Executive Vice Chancellor and Provost Daniel Lowenstein, MD. “To see their passion, commitment, and creativity recognized in this unprecedented number of NIH Director’s Awards is a great honor, for them and for UCSF.”