Bolton, Mullen Recognized for Innovation in Clinical Investigation

Kelly L. Bolton, MD, PhD, an assistant professor of medicine in the Division of Oncology, and Maggie Mullen, MD, an assistant professor of obstetrics and gynecology in the Division of Gynecologic Oncology, both at Washington University School of Medicine in St. Louis, have received grants from the Damon Runyon Cancer Research Foundation for their respective patient-oriented cancer research.

Bolton is one of four recipients nationally of a Continuation Grant, which the foundation awards to previously supported 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. Each Continuation Grant totals $400,000 over two years. She will oversee a clinical trial to evaluate the first use of genetically targeted therapy for cancer prevention.

Mullen is one of six grantees nationally to receive a Clinical Investigator Award, aimed at increasing the number of physicians capable of translating scientific discoveries into new treatments for cancer patients. Each Clinical Investigator Award includes $600,000 over three years, as well as assistance with research costs such as equipment purchases. Damon Runyon also retires up to $100,000 of medical school debt owed by the awardee. Mullen is researching targeted therapies that work with chemotherapy to improve outcomes for patients with advanced ovarian cancer.

Both physician-scientists treat patients at Siteman Cancer Center, based at Barnes-Jewish Hospital and the School of Medicine.

As Damon Runyon grantees, Bolton and Mullen will conduct their research under the mentorship of leading scientists. Bolton is mentored by Matthew J. Walter, MD, the Edward P. Evans Endowed Professor of Myelodysplastic Syndromes in the Division of Oncology at the School of Medicine, and Eytan M. Stein, MD, chief of Leukemia Service at Memorial Sloan Kettering Cancer Center. Mullen is mentored by Dineo Khabele, MD, the Mitchell & Elaine Yanow Professor and chair of the Department of Obstetrics & Gynecology, and Nima Mosammaparast, MD, PhD, a professor of pathology and immunology and co-director of the Physician Scientist Training Program, both at the School of Medicine.

Bolton’s research is focused on myeloid neoplasms (MN), which are blood cancers that include acute myeloid leukemia and myelodysplastic syndrome. The genetic mutations in the blood that lead to MN can occur years before diagnosis and maintain almost normal function before transformation. Certain mutations, including those in the gene IDH2, have been identified as high-risk for developing MN. Individuals with a reduction in the number of mature blood cells (cytopenias) who harbor acquired mutations in their blood, yet do not meet criteria for a cancer diagnosis, have a condition called cytopenias of undetermined significance (CCUS). These individuals almost invariably develop MN. Bolton will conduct a clinical trial to evaluate whether the IDH2 inhibitor enasidenib can be used as a therapy for CCUS. She will assess mechanisms of resistance and determine whether enasidenib can prevent the development of MN.

Mullen’s research is aimed at transforming the care of patients with ovarian cancer by reducing its resistance to traditional chemotherapy. This resistance is due in part to the current lack of targeted therapies that work with chemotherapy. Mullen’s lab has identified a new target, COP9 Signalosome Subunit 5 (COPS5), to treat ovarian cancer. Her team has found that inhibiting COPS5 with a novel drug drastically improves ovarian cancer response to chemotherapy. She now aims to test the effectiveness of this drug and chemotherapy against patient-derived, therapy-resistant ovarian cancer tumors. She will also investigate the mechanism of COPS5, believed to be involved in the repair of DNA damage caused by chemotherapy.