Grants per year
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
1999 | Residency, University of Washington Medical Center |
2000 | Fellowship, University of Michigan Health System |
2002 | Fellowship, Northwestern University, McGaw Medical Center (Northwestern Memorial Hospital) |
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
Education/Academic qualification
MD, Medicine, Harvard University
… → 1996
Research interests keywords
- Cancer Biology
- Cell Biology
- Extracellular Matrix
- Hematology
- Oncology
- Pancreatic Cancer
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Collaborations and top research areas from the last five years
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CCSG Program Leadership
Arispe, L. (Other), Backman, V. (Other), Godley, L. A. (Other), Hitsman, B. L. (Other), Khan, S. A. (Other), Matei, D. E. (Other), Munshi, H. G. (Other), Peter, M. E. (Other), Rini, C. (Other), Shilatifard, A. (Other), Simon, M. A. (Other), Stupp, R. (Other), Wignall, S. (Other), Woloschak, G. E. (Other), Yanez, B. R. (Other) & Zhang, B. (Other)
8/1/23 → 7/31/25
Project: Research project
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VA IPA for Jeffrey Becker FY23
Munshi, H. G. (PD/PI), Munshi, H. G. (PD/PI) & Munshi, H. G. (PD/PI)
5/1/23 → 9/30/25
Project: Research project
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BET Inhibition Rescues Acinar-Ductal-Metaplasia and Ciliogenesis and Ameliorates Chronic Pancreatitis-Driven Changes in Mice with Loss of the Polarity Protein Par3
Shields, M. A., Metropulos, A. E., Spaulding, C., Alzahrani, K. A., Hirose, T., Ohno, S., Pham, T. N. D. & Munshi, H. G., Jan 2024, In: CMGH. 18, 5, 101389.Research output: Contribution to journal › Article › peer-review
Open Access1 Scopus citations -
Loss of STK11 Suppresses Lipid Metabolism and Attenuates KRAS-Induced Immunogenicity in Patients with Non–Small Cell Lung Cancer
Principe, D. R., Pasquinelli, M. M., Nguyen, R. H., Munshi, H. G., Hulbert, A., Aissa, A. F. & Weinberg, F., Aug 2024, In: Cancer Research Communications. 4, 8, p. 2282-2294 13 p.Research output: Contribution to journal › Article › peer-review
Open Access3 Scopus citations -
Regorafenib induces DNA damage and enhances PARP inhibitor efficacy in pancreatic ductal carcinoma
Pham, T. D., Becker, J. H., Metropulos, A. E., Mubin, N., Spaulding, C., Bentrem, D. J. & Munshi, H. G., Dec 2024, In: BMC cancer. 24, 1, 1562.Research output: Contribution to journal › Article › peer-review
Open Access -
Targeting BCL2 with Venetoclax Enhances the Efficacy of the KRASG12DInhibitor MRTX1133 in Pancreatic Cancer
Becker, J. H., Metropulos, A. E., Spaulding, C., Marinelarena, A. M., Shields, M. A., Principe, D. R., Pham, T. D. & Munshi, H. G., Nov 2024, In: Cancer Research. 84, 21, p. 3629-3639 11 p.Research output: Contribution to journal › Article › peer-review
Open Access3 Scopus citations -
Trametinib Potentiates Anti-PD-1 Efficacy in Tumors Established from Chemotherapy-Primed Pancreatic Cancer Cells
Pham, T. D., Metropulos, A. E., Mubin, N., Becker, J. H., Shah, D., Spaulding, C., Shields, M. A., Bentrem, D. J. & Munshi, H. G., Dec 3 2024, In: Molecular cancer therapeutics. 23, 12, p. 1854-1865 12 p.Research output: Contribution to journal › Article › peer-review
1 Scopus citations
Datasets
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CBP bromodomain complexed with YF2-23
Li, Y. (Contributor), Zhao, J. (Contributor), Gutgesell, L. M. (Contributor), Shen, Z. (Contributor), Ratia, K. (Contributor), Dye, K. (Contributor), Dubrovskyi, O. (Contributor), Zhao, H. (Contributor), Huang, F. (Contributor), Tonetti, D. A. (Contributor), Thatcher, G. R. J. (Contributor), Xiong, R. (Contributor), Principe, D. R. (Contributor), Pham, T. N. D. (Contributor), Kamath, S. D. (Contributor), Thummuri, D. (Contributor), Daohong, Z. (Contributor), Underwood, P. W. (Contributor), Trevino, J. (Contributor), Munshi, H. G. (Contributor) & Rana, A. (Contributor), Protein Data Bank (PDB), Sep 1 2021
DOI: 10.2210/pdb7JUO/pdb, https://www.wwpdb.org/pdb?id=pdb_00007juo
Dataset