The Damon Runyon Cancer Research Foundation named five new Damon Runyon Clinical Investigators at its spring 2011 Clinical Investigator Award Committee review. The recipients of this prestigious three-year 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. Each will receive $450,000 to support the development of his/her cancer research program.
The Foundation also awarded Continuation Grants to four Damon Runyon Clinical Investigators. Each award will provide an additional two years of funding totaling $300,000. The Continuation Grant is designed to support Clinical Investigators who are approaching the end of their original awards and need extra time and funding to complete a promising avenue of research or initiate/continue a clinical trial. This program is possible through the generous support of the William K. Bowes, Jr. Foundation, and Connie and Robert Lurie.
The Clinical Investigator Award program is specifically intended to help address the shortage of physicians capable of translating scientific discovery into new breakthroughs for cancer patients. In partnerships with industry sponsors and through its new Accelerating Cancer Cures initiative, the Damon Runyon Cancer Research Foundation has committed more than $38 million to support the careers of 58 physician-scientists across the United States since 2000.
2011 Clinical Investigator Awardees
Marie Bleakley, MD [Richard Lumsden Foundation Investigator]
Bone marrow transplantation, or allogeneic hematopoietic stem cell transplant (HCT), is the only curative therapy for many patients with leukemia. Certain immune cells, called T cells, contained in the donor HCT graft can cause a "graft versus leukemia" (GVL) effect which eliminates leukemic cells. Unfortunately, there are also donor T cells in the HCT graft that can cause a condition called "graft versus host disease" (GVHD). GVHD is a life-threatening immune response that remains the major barrier to the success of transplantation.
Dr. Bleakley focuses on developing new approaches to separate the beneficial GVL effect from detrimental GVHD after bone marrow transplantation. Her goal is to identify specific subsets of immune cells that promote GVHD; these cells can then be eliminated to reduce the frequency or severity of GVHD, while at the same time maintaining and improving the GVL effect. In addition, she aims to discover novel leukemia-associated proteins that could be potential targets for therapeutics.
Dr. Bleakley works under the mentorship of Stanley R. Riddell, MD, at the Fred Hutchinson Cancer Research Center, Seattle, Washington.
Ralph J. DeBerardinis, MD, PhD
Cancer cells use specific metabolic pathways to fuel their growth into tumors. A great deal of work has already defined some of these pathways that allow cancer cells to grow in the laboratory, but very little is known about which pathways drive the growth of actual tumors in cancer patients.
Dr. DeBerardinis aims to understand the role of metabolism in tumor growth and to use these findings to improve treatment of cancer. He plans to use novel, highly sensitive methods to study metabolic activity in vivo in primary human glioma brain tumors, and to image these activities in growing tumors. This approach should also be applicable to other cancer types and will be important for disease imaging and therapy.
Dr. DeBerardinis works under the mentorship of Helen H. Hobbs, MD, at the University of Texas Southwestern Medical Center, Dallas, Texas.
Joshua D. Schiffman, MD
Ewing's sarcoma is the second most common bone tumor in children and adolescents. Patients have a poor prognosis, yet the causes of the disease are not understood. Certain genetic changes have been linked to Ewing's sarcoma: a specific translocation (joining of two different chromosome parts) and microsatellites (series of repeating DNA sequences). Another reported observation is increased development of hernias in patients with this disease.
Dr. Schiffman, a pediatric oncologist, is interested in understanding the underlying molecular genetics of Ewing's sarcoma. He will take a genetic epidemiologic approach to studying the disease, by examining the genes of parent-child trios: patients with Ewing's sarcoma and their parents. He will examine inheritance of DNA microsatellites and genetic changes associated with hernia development. This study will identify novel genetic risk factors for Ewing's sarcoma, which can be used for future preventative and therapeutic strategies.
Dr. Schiffman works under the mentorship of Stephen L. Lessnick, MD, PhD, at the University of Utah, Salt Lake City, Utah.
Zsofia K. Stadler, MD
Heritable factors are an important determinant of cancer risk. At present, a large portion of the genetic basis of cancer predisposition remains unexplained.
Dr. Stadler is a clinical geneticist whose research goal is to determine the genetic basis of "sporadic" cancers in young adults. She will be testing the hypothesis that de novo (spontaneous) chromosomal changes in the genome are associated with testicular germline cancer. High-resolution sequencing technology will be used to compare the whole genomes of patients to those of their parents, with the goal of identifying rare genetic variants associated with cancer susceptibility. This approach represents a new paradigm in cancer genetics, which could have broad applications in terms of cancer risk stratification and cancer prevention.
Dr. Stadler works under the mentorship of Kenneth Offit, MD, MPH, and Michael H. Wigler, PhD, at Memorial Sloan-Kettering Cancer Center, New York, New York.
Jean Y. Tang, MD, PhD
Basal cell carcinoma (BCC) is the most common type of skin cancer. Mutations in the Hedgehog (HH) signaling pathway are frequently found in these cancers. Early-stage clinical studies of a HH pathway inhibitor drug have been successful, with 55% of patients reported to respond. However, most tumors change during the course of therapy and drug resistance eventually develops.
Dr. Tang, a dermatologist, will characterize mechanisms of drug resistance and identify new drug combinations that are effective in treatment of BCC. The ultimate goal of her research is to prevent or delay drug resistance. Her studies have the potential to benefit patients with BCC as well as those with other HH-dependent cancers, such as medulloblastoma.
Dr. Tang works under the mentorship of Philip A. Beachy, PhD, and Ervin H. Epstein, MD, at Stanford University, Stanford, California.
2011 Clinical Investigator Continuation Grants
Andrew T. Chan, MD, MPH
Dr. Chan is developing molecular "smart" probes and novel imaging techniques for earlier and improved detection of colorectal cancer. The Continuation Grant will be used to complete a clinical trial testing an innovative high-definition non-fiberoptic imaging system for both colonoscopy and upper endoscopy. This work also has the potential to accelerate the discovery and development process for therapeutic and chemopreventative agents in colorectal cancer.
Dr. Chan works under the mentorship of Charles S. Fuchs, MD, MPH, and Ralph Weissleder, MD, PhD, at Massachusetts General Hospital, Boston, Massachusetts.
Rachael A. Clark, MD, PhD
Dr. Clark has made important findings on the role of immune T cells in skin cancers, particularly squamous cell carcinomas and cutaneous T cell lymphoma. The Continuation Grant will allow her to expand her research to Merkel cell carcinoma (MCC), a highly malignant skin cancer associated with a novel polyoma virus. She plans to characterize T cells present in MCC. The goal is to use this information to better identify patients at risk for this cancer and to develop novel effective tumor vaccines.
Dr. Clark works under the mentorship of Thomas S. Kupper, MD, at Brigham and Women's Hospital, Boston, Massachusetts.
Vassiliki Karantza, MD, PhD
Dr. Karantza is examining the role of autophagy in tumor cell survival and responsiveness to chemotherapy. Autophagy is a process of "cellular self-digestion" that is used by both normal cells and tumor cells as a survival mechanism in times of metabolic stress, such as nutrient and oxygen deprivation. She will use the Continuation Grant to pursue novel studies examining the role of autophagy in pregnancy-associated breast cancer. She also plans to conduct a clinical trial combining autophagy inhibition with other existing therapies for treatment of certain types of pancreatic cancer, for which there is a need for more effective treatment options.
Dr. Karantza works under the mentorship of Robert S. DiPaola, MD, at UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey.
Elahe A. Mostaghel, MD, PhD [Genentech Investigator]
Dr. Mostaghel is defining key mechanisms underlying resistance of prostate cancer to hormone treatment. Suppression of the hormone testosterone is currently the most effective treatment for advanced prostate cancer; however, tumors frequently develop resistance to this therapy. The Continuation Grant will enable her to continue developing novel treatments for prostate cancer that can be rapidly moved into the clinic.
Dr. Mostaghel works under the mentorship of Peter S. Nelson, MD, at the Fred Hutchinson Cancer Research Center, Seattle, Washington.
Unlocking glioblastoma's immune suppression mechanism