Carl DeSelm, MD, PhD

Carl DeSelm, MD, PhD

Assistant Professor of Radiation Oncology

Education

  • BA, Genetics, Cell, and Developmental Biology: Dartmouth College, Hanover, NH (2004)
  • MD: Washington University School of Medicine, St. Louis, MO (2012)
  • PhD, Molecular and Cellular Biology (Focus: Osteoimmunology): Washington University, St. Louis, MO (2012)
  • Internship, Internal Medicine: Barnes-Jewish Hospital, St. Louis, MO (2013)
  • Residency, Radiation Oncology: Memorial Sloan Kettering Cancer Center, New York, NY (2017)
  • Holman Research Fellowship: Memorial Sloan Kettering Cancer Center, New York, NY (2016-2017)
  • Translational Research Fellowship: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY (2017-2018)

Recognition

  • Ruth L. Kirschstein National Research Service Award (2009)
  • Young Investigator Award: American Society for Bone and Mineral Research (2009)
  • Merit Award: Division Of Biology and Biomedical Sciences, Washington University in St. Louis (2011)
  • Needleman Pharmacology Award: Department of Developmental Biology, Washington University in St. Louis (2012)
  • Holman Research Pathway (2017)
  • Agilent Early Career Professor Award (2020)

Clinical Interests

SBRT or ablative radiation for cancers of the liver, pancreas, or gallbladder, as well as liver metastases

Biography

Carl DeSelm, MD PhD, joined the Washington University faculty in June 2018 as an assistant professor of Radiation Oncology with a laboratory in the Bursky Center for Human Immunotherapy and Immunology Programs (CHiiPs). After earning his undergraduate degree from Dartmouth College, Dr. DeSelm earned his MD and PhD from Washington University School of Medicine in 2012, during which time he studied under Dr. Steven Teitelbaum. As a PhD student, Dr. DeSelm described a secretory pathway in the bone resorbing osteoclast that utilizes authophagy pathway proteins, and characterized the role of IL-17 in the pathogenesis of osteoporosis. His work led to the Needleman Pharmacology Award from Washington University and a patent for a new therapy for osteoporosis. Dr. DeSelm subsequently redirected his energy toward oncology, and after completing an internal medicine year at Washington University’s Barnes Jewish Hospital, underwent radiation oncology residency training at Memorial Sloan Kettering Cancer Center (MSKCC) in New York. During his time at MSKCC, he became highly interested in immunotherapy, in particular CAR T cell therapy, as some of the first leukemia patients treated with the novel therapy began to exhibit remarkable responses. This prompted him to join the laboratory of Dr. Michel Sadelain, a founding member of the field of CAR T cell therapy, as a Holman Research Fellow. Upon finishing residency, Dr. DeSelm completed a Translational Research Fellowship at MSKCC, continuing to study the combination of radiation with cellular immunotherapy under Michel Sadelain. Currently, Dr. DeSelm clinically focuses on treating lymphoma, and is actively developing novel CAR T cell approaches to treating solid tumors, including lymphoma, pancreatic cancer and glioblastoma.

Research

Dr. DeSelm’s research is based upon several fundamental ideas that have surfaced in recent decades. The first is that within each patient are immune cells dedicated to finding and destroying microscopic organisms that are far more sophisticated than any drug developed by man. The second is that these immune cells, generally T cells, can be modified to find and destroy tumor cells, using a chimeric antigen receptor (CAR). Using this approach, large, advanced, or aggressive cancers can sometimes be completely eliminated after a single treatment with the patient’s own modified immune cells. A major question remains – how do we achieve this result for all cancers, and all patients.

One major obstacle to applying this technique to all cancers is the difficulty in finding target molecules that are only expressed on the tumor cells, and not on critical normal tissues. Further, if not every tumor cell expresses the target molecule, the cancer will not be cured, as the negative cells that escape will eventually grow back. One major focus of the lab is identifying novel ways by which CAR cellular therapy can overcome the problem of antigen escape, to fully eliminate disseminated, heterogeneous cancer cells.

Additional problems exist in solid tumors, including poor penetration of the tumor by CAR T cells, and inherent resistance of particular tumors to T cell killing. The mechanisms by which these occur, and methods to overcome them, are active areas of investigation within the laboratory.

Radiation therapy is known to modulate the immune response in a variety of ways, but its effect on cellular therapy is poorly understood. An additional major focus in the laboratory is to examine the effect of radiation therapy on the systemic and local tumor response to CAR T cell therapy, and develop CARs that function synergistically with radiation and other highly effective treatment modalities.

Publications

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(Disclaimer: This listing may not include all articles associated with this faculty member and may include publications related to others with a similar name.)

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