Mandar Deepak Muzumdar, MD

Assistant Professor

Research Departments & Organizations

Internal Medicine: Medical Oncology

Yale Cancer Biology Institute

Yale Cancer Center: Genomics, Genetics, and Epigenetics

Yale Cancer Biology Institute

Research Interests

Adaptation, Biological; Animals, Genetically Modified; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Cell Proliferation; Genes, Tumor Suppressor; MAP Kinase Signaling System; Obesity; Oncogenes; Precancerous Conditions

Research Summary

Despite innovations in combination chemotherapy, targeted therapies, and immunotherapies, most advanced cancers remain incurable. Deciphering the mechanisms that govern the initiation, progression, and maintenance of cancer will facilitate the development of novel strategies for prevention and therapy. For cancers to arise, cells must acquire the capacity for sustained proliferation while overcoming both intrinsic evolutionary constraints and constraints imposed by the host environment. These properties may be attained through the sequential acquisition of genetic mutations in proto-oncogenes and tumor suppressor genes. Comprehensive genome sequencing efforts have catalogued human cancer mutations, enabling the use of therapies that target these mutated oncoproteins. Nonetheless, cancers frequently evade target inhibition. We recently demonstrated, for example, that pancreatic cancer cells tolerate genetic ablation of their initiating oncogene KRAS through rewiring of signal transduction. Similar adaptive mechanisms (signaling-based, transcriptional, epigenetic, and metabolic) play a critical role in the maintenance of advanced cancers in the absence of new mutations. In contrast, how non-mutational adaptations impact the earlier stages of tumorigenesis remains poorly understood.

Using genetically-engineered mouse models that closely recapitulate human lung and pancreatic cancers, we have shown that gene mutations are permissive, but insufficient, to drive clonal cancer evolution, consistent with the need for additional cellular adaptations. Furthermore, we have demonstrated that host adaptations to environmental stresses, such as obesity, may facilitate tumor progression in the absence of new mutations. Our research focuses on elucidating the molecular basis of these tumor cell and host adaptations in hopes of defining new approaches for the prevention and treatment of these recalcitrant cancers.



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Contact Info

Mandar Deepak Muzumdar, MD
Lab Location
Sterling Hall of Medicine
333 Cedar Street, Wing B-Wing Fl 3rd Floor Rm B323

New Haven, CT 06510
Office Locations
Yale Cancer Biology InstituteWest Campus Advanced Biosciences Center
840 West Campus Drive

West Haven, CT 06516
GeneticsSterling Hall of Medicine, B-Wing
333 Cedar Street

New Haven, CT 06510
Mailing Address
GeneticsYale University School of Medicine
Department of Genetics, P.O. Box 208005

New Haven, CT 06520-8005

Muzumdar Lab