• 2621 Citations
1992 …2023

Research output per year

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Personal profile

Research Interests

I have a long-term interest in understanding the role of the pronounced collagen-rich stromal reaction that is present in human pancreatic tumors. We have shown that the cancer cells upregulate the key collagenase MT1-MMP to invade and grow in 3D collagen. Recently, we developed a novel method to track cell invasion in 3D collagen using MT1-MMP-expressing cancer cells and found that Ga13 and DDR1-Par3 signaling differentially mediate invasion in the collagen-rich microenvironment. Besides studying the mechanisms by which collagen microenvironment regulates invasion, we are also interested in understanding the role of the collagen microenvironment in treatment resistance, and have shown that epigenetic changes induced by the collagen microenvironment contribute to resistance to chemotherapy. We have found that collagen microenvironment induces histone acetylation and that targeting “readers” of histone acetylation marks using BET inhibitors can limit growth of pancreatic cancer cells. We are currently evaluating BET inhibitors in mouse models of pancreatic cancer with the goal of eventually translating these inhibitors to studies in pancreatic cancer patients. Our ongoing work suggests that BET inhibitors, a number of which are currently being evaluated in clinical trials, will have to be combined with other therapies for maximal clinical efficacy. Finally, we have begun studies evaluating how the collagen microenvironment regulates mRNA translation to mediate pancreatic cancer progression. We have found that pharmacologic and genetic targeting of MNKs, which regulate mRNA translation, can block pancreatic cancer development and progression. We are working to translate these results with BET and MNK inhibitors into clinical trials for patients with pancreatic cancer.

Certifications and Licenses

Hematology
Medical Oncology
Internal Medicine

Training Experience

1999Residency, University of Washington Medical Center
2000Fellowship, University of Michigan Health System
2002Fellowship, Northwestern University, McGaw Medical Center (Northwestern Memorial Hospital)

Education/Academic qualification

MD, Harvard University

… → 1996

Research interests

  • Cancer Biology
  • Cell Biology
  • Extracellular Matrix
  • Hematology
  • Oncology
  • Pancreatic Cancer

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Grants

Research Output

Metastatic Thymoma Harboring a Deleterious BRCA2 Mutation Derives Durable Clinical Benefit from Olaparib

Principe, D. R., Kamath, S. D., Munshi, H. G. & Mohindra, N. A., Apr 1 2020, In : Oncologist. 25, 4, p. 301-305 5 p.

Research output: Contribution to journalArticle

Open Access
  • Alveolar soft part sarcoma mimics prostate cancer metastasis

    Principe, D. R., Mohindra, N. A., Munshi, H. G. & Kamath, S. D., Dec 1 2019, In : Oxford Medical Case Reports. 2019, 12, p. 507-509 3 p.

    Research output: Contribution to journalArticle

    Open Access
  • Induction of MNK kinase–dependent eIF4E phosphorylation by inhibitors targeting BET proteins limits efficacy of BET inhibitors

    Pham, T. N. D., Kumar, K., DeCant, B. T., Shang, M., Munshi, S. Z., Matsangou, M., Ebine, K. & Munshi, H. G., Feb 2019, In : Molecular cancer therapeutics. 18, 2, p. 235-244 10 p.

    Research output: Contribution to journalArticle

  • 2 Scopus citations

    P110γ deficiency protects against pancreatic carcinogenesis yet predisposes to diet-induced hepatotoxicity

    Torres, C., Mancinelli, G., Cordoba-Chacon, J., Viswakarma, N., Castellanos, K., Grimaldo, S., Kumar, S., Principe, D., Dorman, M. J., McKinney, R., Hirsch, E., Dawson, D., Munshi, H. G., Rana, A. & Grippo, P. J., Jan 1 2019, In : Proceedings of the National Academy of Sciences of the United States of America. 116, 29, p. 14724-14733 10 p.

    Research output: Contribution to journalArticle

  • 1 Scopus citations

    Potent antineoplastic effects of combined PI3Kα-MNK inhibition in medulloblastoma

    Eckerdt, F., Bell, J. B., Beauchamp, E. M., Clymer, J., Blyth, G. T., Kosciuczuk, E. M., Ma, Q., Chen, D. Z., Horbinski, C., Goldman, S., Munshi, H. G., Hashizume, R. & Platanias, L. C., Jun 1 2019, In : Molecular Cancer Research. 17, 6, p. 1305-1315 11 p.

    Research output: Contribution to journalArticle

  • 2 Scopus citations