Princess Margaret Cancer Centre
Overview
The Kirsch Lab uses sophisticated genetically engineered mouse models, cellular and molecular biology and biochemistry to study cancer and radiation biology. Our research ranges from fundamental basic questions into the mechanisms by which tumor suppressor genes prevent cancer to translational projects that focus on mechanisms of metastasis, tumor response to radiation therapy and normal tissue injury from radiation. In a collaborative environment, we work together to make discoveries and strive to translate our research into clinical trials for patients with cancer.
Short Bio
David Kirsch, MD, PhD, is a Senior Scientist at Princess Margaret Cancer Centre and the Peter and Shelagh Godsoe Chair in Radiation Medicine. After graduating from Duke University with a BS in Biology, he completed the MD/PhD program at Johns Hopkins School of Medicine, where he performed his thesis research with Dr. Michael Kastan. Dr. Kirsch completed residency training in radiation oncology at Massachusetts General Hospital and a post-doc in the laboratory of Dr. Tyler Jacks at MIT. In 2007 Dr. Kirsch returned to Duke, to establish an independent research program. In 2023, Dr. Kirsch was recruited to Princess Margaret Cancer Centre at University Health Network. He has received a number of awards for his research including the 2010 Michael Fry Award and the 2017 J.W. Osborne Award from the Radiation Research Society. Dr. Kirsch has been elected to the American Society for Clinical Investigation, the Association of American Physicians, a Fellow of the American Society for Radiation Oncology, and a Fellow of the American Association for the Advancement of Science. He has also received several awards for mentoring including the 2014 Duke University Dean’s Award for Excellence in Mentoring and the 2021 Career Mentoring Award in Basic/Translational Science from the Duke University School of Medicine.
Recent Publications
p53 promotes revival stem cells in the regenerating intestine after severe radiation injury.
Morral C, Ayyaz A, Kuo HC, Fink M, Verginadis I, Daniel AR, Burner DN, Driver LM, Satow S, Hasapis S, Ghinnagow R, Luo L, Ma Y, Attardi LD, Koumenis C, Minn AJ, Wrana JL, Lee CL, Kirsch DG. bioRxiv. 2023 Apr 28:2023.04.27.538576. doi: 10.1101/2023.04.27.538576. Preprint.PMID: 37162959
Floyd W, Pierpoint M, Su C, Patel R, Luo L, Deland K, Wisdom AJ, Zhu D, Ma Y, DeWitt SB, Williams NT, Lazarides AL, Somarelli JA, Corcoran DL, Eward WC, Cardona DM, Kirsch DG. J Clin Invest. 2023 Jul 3;133(13):e149310. doi: 10.1172/JCI149310.PMID: 37200088
Himes JE, Wisdom AJ, Wang L, Shepard SJ, Daniel AR, Williams N, Luo L, Ma Y, Mowery YM, Kirsch DG. bioRxiv. 2023 Apr 6:2023.04.04.535550. doi: 10.1101/2023.04.04.535550. Preprint.PMID: 37066384
Research Programs
Mouse models of sarcoma
Normal tissue injury from radiation
Normal tissue injury from radiation
We study mechanisms of sarcoma development and tumour maintenance in undifferentiated small round cell sarcoma driven by the CIC-DUX4 fusion oncoprotein and in epithelioid sarcoma initiated by loss of SMARCB1, a subunit of the SWI/SNF protein complex.
Normal tissue injury from radiation
Normal tissue injury from radiation
Normal tissue injury from radiation
We use Cre-loxP technology to delete genes in a cell-type specific manner and apply sophisticated small animal irradiation to study mechanisms of radiation injury and regeneration in the intestine and other tissues.
Sarcoma response to Immunotherapy
Normal tissue injury from radiation
Sarcoma response to Immunotherapy
Using autochthonous sarcoma models, we study mechanisms of tumour response to radiotherapy alone or to a combination of radiation and immunotherapy.
Transposon biology in oncogenesis
Normal tissue injury from radiation
Sarcoma response to Immunotherapy
We also study mechanisms of tumour suppression by the three genes most frequently mutated in complex karyotype sarcomas like undifferentiated pleomorphic sarcoma: p53, Rb, and ATRX. We investigate the link between loss of tumor suppressors, the derepression of transposable elements, and the regulation of 3D DNA topology.