Damon Runyon Cancer Research Foundation names five new Damon Runyon Clinical Investigators
The Damon Runyon Cancer Research Foundation has named five new Damon Runyon Clinical Investigators. The recipients of this prestigious award are outstanding, early-career physician-scientists conducting patient-oriented cancer research at major research centers under the mentorship of the nation’s leading scientists and clinicians.
The Clinical Investigator Award program was designed to help address the shortage of physicians capable of translating scientific discovery into new breakthroughs for cancer patients. Each awardee will receive $600,000 over three years, as well as assistance with research costs such as the purchase of equipment. Because the need to repay medical school loans is often cited as a deterrent to pursuing research, Damon Runyon will also retire up to $100,000 of medical school debt owed by the awardee.
The Foundation also awarded Continuation Grants to three Damon Runyon Clinical Investigators for an additional two years of funding, totaling $400,000 each. The Continuation Grants are designed to support Clinical Investigators who are approaching the end of their original award and need more time to work on a promising avenue of research or a clinical trial. This program is possible through the generous support of the William K. Bowes, Jr. Foundation.
“The quality of research proposed by our Clinical Investigators is exceptionally strong. We are thrilled to be funding brave and bold physician-scientists who are taking risks to experimentally address the most important questions in cancer research and then translate them into improving patients’ lives,” says Yung S. Lie, PhD, Damon Runyon’s President and Chief Executive Officer. “We are helping to launch the careers of tomorrow’s brightest cancer researchers.”
Through partnerships with generous donors, industry sponsors, and its Accelerating Cancer Cures initiative, the Damon Runyon Cancer Research Foundation has committed over $80 million to support the careers of 119 physician-scientists across the United States since 2000.
2022 Clinical Investigators
Daniel J. Delitto, MD, PhD, with mentor Michael T. Longaker, MD, DSc, at Stanford University, Stanford
Pancreatic cancer develops in the midst of intense scarring and fibrous connective tissue (fibrosis). The architects of this scarring are cells called fibroblasts, known to fuel cancer growth and promote treatment resistance. Dr. Delitto’s research is focused on the interface between cancer-induced fibrosis and the immune system. He has shown that fibroblasts play a significant role in shielding cancer cells from immune cells. By altering how fibroblasts sense tissue damage, Dr. Delitto has uncovered a mechanism that reactivates the immune system to fight the tumor. He aims to further develop these findings into a novel immunotherapy regimen for pancreatic cancer.
Xiuning Le, MD, PhD, with mentor John V. Heymach, MD, PhD, at University of Texas MD Anderson Cancer Center, Houston
Mutations in the EGFR gene were identified as the first targetable mutations in lung cancer about two decades ago. Since then, multiple targeted therapies have been approved and prolonged many lives. However, about 15% of EGFR mutations are atypical and do not have a current approved targeted therapy. Dr. Le is leading multiple clinical trials to address this unmet need. With new treatments potentially entering the clinic, new mechanisms of treatment resistance will likely evolve. Dr. Le aims to comprehensively characterize resistance mechanisms and compare resistance predisposition across different types of EGFR-linked lung cancers. She will leverage cutting-edge techniques to determine the mutations at single-cell level and develop rational therapeutic strategies to overcome resistance. This project has the potential not only to bring new FDA-approved treatments to patients but also establish clinical strategies to predict and target major resistance mechanisms.
Nathan Singh, MD [Bakewell Foundation Clinical Investigator], with mentor John F. DiPersio, MD, PhD, at Washington University, St. Louis
Chimeric antigen receptor T cell (CAR T cell) therapy, in which a patient’s own immune cells are engineered to target their cancer, has changed the treatment landscape for many blood cancers. Despite promising early results, however, long-term follow-up has revealed that nearly half of patients treated with CAR T cells eventually experience cancer recurrence. Using a variety of techniques in cell lines and patient samples, Dr. Singh aims to understand how interactions between engineered T cells and blood cancer cells in some cases lead to long-term remission, and in others to therapeutic failure. The broad goals of his lab are to understand the biological signals that cause these therapies to fail, and to use this knowledge to design next-generation immunotherapies that can cure more patients.
Melody Smith, MD, with mentor Robert S. Negrin, MD, at Stanford University, Stanford
The microorganisms that live in the digestive tract, also known as the intestinal microbiome, have emerged as important factors in patients’ response to cancer therapy. Studies have found that the intestinal microbiome can modulate the anti-tumor immune response to several types of therapy, including chimeric antigen receptor T cell (CAR T cell) therapy, in which a patient’s own immune cells are genetically modified to target their cancer. CAR T therapy has led to unprecedented responses in patients with high-risk blood cancers such as leukemia and lymphoma. However, patients may experience disease relapse or CAR-mediated toxicities. Dr. Smith has found that responses to CAR T therapy are linked to alterations in and abundances of the intestinal microbiome. Her research will investigate how the intestinal microbiome mediates this impact on CAR T cells. Dr. Smith was previously a Damon Runyon Physician-Scientist, a complementary award program designed for clinicians interested in research to acquire the skills needed to become physician-scientists.
Aaron D. Viny, MD [Damon Runyon-Doris Duke Clinical Investigator], with mentors Emmanuelle Passegué, PhD, and Joseph G. Jurcic, MD, at Columbia University, New York
Up to 50% of patients with acute myeloid leukemia (AML) have a genetic alteration called DNA methylation, in which a carbon methyl group is added to the DNA molecule, typically turning the methylated gene “off.” A mainstay of therapy is the use of hypomethylating agents, which prevent copying of these modifications during cell division, but this therapy is effective in only 20-30% of patients. Using chemical and genetic manipulation in mouse bone marrow, Dr. Viny aims to determine the effect of DNA methylation on the ability of specific regions of the genome to be accessible to proteins involved with gene expression and other regions to be inaccessible and “silenced.” In a prospective phase II clinical trial, he will treat relapsed AML patients with dual hypomethylating agents. By studying these patients’ genetic profiles, he aims to determine the genetic features that contribute to therapy response, paving the way for more effective interventions to be developed for patients with acute myeloid leukemia. Dr. Viny was previously a Damon Runyon Fellow.
2022 Continuation Grantees
Jennifer M. Kalish, MD, PhD, with mentors Marisa S. Bartolomei, PhD, and Garrett M. Brodeur, MD, at Children’s Hospital of Philadelphia, Philadelphia
Dr. Kalish is studying a rare hereditary syndrome called Beckwith-Wiedemann syndrome (BWS), which increases the risk of children developing kidney and liver cancers. These individuals have epigenetic changes on chromosome 11 that are found in other types of cancers. Epigenetic markers modify DNA so gene expression is turned on or off; changes in this process can cause cancer. By understanding how cancer is triggered in BWS, Dr. Kalish aims to identify pathways that can be targeted for the development of new treatments both for BWS patients and for others with cancers that have similar epigenetic changes. As a physician-scientist, Dr. Kalish established the BWS Registry, which compiles both clinical data and patient samples, and created the first human cell-based models of BWS.
Matthew G. Oser, MD, PhD, with mentor William G. Kaelin, Jr., MD, at Dana-Farber Cancer Institute, Boston
Although small cell lung cancer (SCLC) is initially highly responsive to chemotherapy, the disease recurs in nearly all patients in less than a year. There are currently no approved targeted therapies for when the cancer returns. Previous studies have demonstrated that SCLCs require sustained neuroendocrine differentiation for survival, suggesting that targeting this process could be a good therapeutic strategy. Dr. Oser will use SCLC patient-derived xenograft models and a novel SCLC genetically engineered mouse model to identify new enzymes required for neuroendocrine differentiation and to develop targeted therapies that can block this process. He aims to identify molecular targets that could be developed into new lasting therapies for SCLC patients.
Kavita Y. Sarin, MD, PhD [D.G. ‘Mitch’ Mitchell Clinical Investigator], with mentors Jean Y. Tang, MD, PhD, and Anthony E. Oro, MD, PhD, at Stanford University, Stanford
Basal cell cancer (BCC) is the most common cancer in the United States with 2 million cases annually resulting in $5 billion in societal cost. Although the majority of BCCs are small and surgically accessible, some individuals develop frequent recurrences of BCC and suffer from severe disability related to surgery and decreased quality of life. Dr. Sarin will focus on a group of 100 patients who develop extreme numbers of this skin lesion, in order to identify the genetic mechanisms that contribute to cancer susceptibility. While most BCCs are thought to develop from DNA damage caused by the sun’s ultraviolet rays, a patient’s genetics also play a critical role in disease progression. Understanding the mechanisms that contribute to cancer susceptibility will help identify at-risk individuals so they can be monitored for earlier diagnosis and prevention. She also aims to develop new non-surgical therapies for these patients.