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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

Keywords

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

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Grants 2003 2023

Pancreatic Neoplasms
Adenocarcinoma
Organoids
Collagen
Transgenic Mice
Adenocarcinoma
Collagen
varespladib methyl
Fibrosis
Small Interfering RNA
Pancreatic Neoplasms
Adenocarcinoma
Collagen
varespladib methyl
Fibrosis

VA IPA for Meng Shang

Munshi, H. G.

Jesse Brown VA Medical Center

10/1/176/30/18

Project: Research project

Pancreatic Neoplasms
Neoplasms
Neoplasm Genes
Pancreatitis
Drinking

Research Output 1992 2019

Quantitative method to track proteolytic invasion in 3D collagen

Ebine, K., Chow, C. R. & Munshi, H. G., Jan 1 2019, Methods in Molecular Biology. Humana Press Inc, p. 161-169 9 p. (Methods in Molecular Biology; vol. 1882).

Research output: Chapter in Book/Report/Conference proceedingChapter

Collagen
Neoplasms
Gels

Interplay between interferon regulatory factor 1 and BRD4 in the regulation of PD-L1 in pancreatic stellate cells

Ebine, K., Kumar, K., Pham, T. N., Shields, M. A., Collier, K. A., Shang, M., DeCant, B. T., Urrutia, R., Hwang, R. F., Grimaldo, S., Principe, D. R., Grippo, P. J., Bentrem, D. J. & Munshi, H. G., Dec 1 2018, In : Scientific Reports. 8, 1, 13225.

Research output: Contribution to journalArticle

Pancreatic Stellate Cells
Interferon Regulatory Factor-1
Interferon-gamma
Adenocarcinoma
Stromal Cells

KRASG12D and TP53R167H Cooperate to Induce Pancreatic Ductal Adenocarcinoma in Sus scrofa Pigs

Principe, D. R., Overgaard, N. H., Park, A. J., Diaz, A. M., Torres, C., McKinney, R., Dorman, M. J., Castellanos, K., Schwind, R., Dawson, D. W., Rana, A., Maker, A., Munshi, H. G., Rund, L. A., Grippo, P. J. & Schook, L. B., Dec 1 2018, In : Scientific Reports. 8, 1, 12548.

Research output: Contribution to journalArticle

Sus scrofa
Pancreatic Ducts
Adenocarcinoma
Swine
Translational Medical Research

Nab-Paclitaxel and Gemcitabine as First-line Treatment of Advanced or Metastatic Cholangiocarcinoma: A Phase 2 Clinical Trial

Sahai, V., Catalano, P. J., Zalupski, M. M., Lubner, S. J., Menge, M. R., Nimeiri, H. S., Munshi, H. G., Benson III, A. B. & O'Dwyer, P. J., Jan 1 2018, (Accepted/In press) In : JAMA Oncology.

Research output: Contribution to journalArticle

gemcitabine
Cholangiocarcinoma
Clinical Trials
Disease-Free Survival
Nanoparticles

Slfn2 regulates type I interferon responses by modulating the NF-κB pathway

Fischietti, M., Arslan, A. D., Sassano, A., Nora Vaz Saleiro, D., Majchrzak-Kita, B., Ebine, K., Munshi, H. G., Fish, E. N. & Platanias, L. C., Aug 1 2018, In : Molecular and cellular biology. 38, 16, e00053-18.

Research output: Contribution to journalArticle

Interferon Type I
Interferons
Genes
NF-kappa B
Antiviral Agents