MEMP PhD Thesis Defense: Dennis Gong

Understanding Treatment Resistance and Residual Disease in Pancreatic Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one the most aggressive, treatment resistant, and deadliest cancer types. Multiagent chemotherapy is currently the standard of care, but recently KRAS inhibitors, which target gain of function KRAS mutations in >95% of PDAC patients, have entered clinical trials and reported unprecedented improvements in response rates and overall survival. Still, PDAC tumors continue to eventually resist both broad cytotoxic chemotherapy and KRAS targeted regimens, leaving surgery as the only curative treatment modality for the minority patients who are eligible. However, even surgery leaves traces of residual disease, and recurrence occurs in roughly 80% of patients. This dissertation uses multi-modal tools and diverse experimental approaches to characterize, understand, and target the biology of treatment resistant and residual disease. First, I develop and apply new methods to integrate morphological profiling with molecular characterization across many patient derived cell lines, revealing treatment induced effects on cancer cell state. Next, I perform detailed spatial and multi-omic characterization of a neural-like progenitor cell state, which is enriched in residual disease in patient tumors. Finally, I perform unbiased transcription factor overexpression screens to identify genetic factors that enable treatment resistance. Altogether, we identify and characterize new mechanisms of treatment resistance and persistence in residual disease, motivating therapeutic strategies for this deadly disease.

Thesis Supervisor:
William Hwang, MD, PhD
Assistant Professor of Radiation Oncology, Harvard Medical School
Associate Director, Radiation Biology & Research Program at Massachusetts General Hospital

Thesis Committee Chair:
Angela Koehler, PhD
Professor of Biological Engineering, MIT 
Associate Director, David H. Koch Institute for Integrative Cancer Research at MIT 
Faculty Director, MIT Health and Life Sciences Collaborative

Thesis Readers:
Nabeel Bardeesy, PhD
John R. Gallagher III and Katherine A. Gallagher Endowed Chair in Gastrointestinal Cancer Research
Professor of Medicine, Harvard Medical School

David Ting, MD
Associate Clinical Director of Innovation, Cancer Center, Massachusetts General Hospital
Cancer Institute Amin and Zebunisha Juma Endowed Chair in Oncology 
Associate Professor of Medicine, Harvard Medical School

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Dennis Gong is inviting you to a scheduled Zoom meeting

Topic: Dennis Gong MEMP PhD Thesis Defense
Time: Monday, April 27, 2026, 11:00 AM Eastern Time (US and Canada)

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