Oncogenes, tumor suppressor genes, molecular genetics of GI cancers (colon, pancreatic, upper GI)
Cancers: esophageal, pancreatic, colon Oncogenes: EGFR, cyclin D1, Ki-Ras Organotypic culture
Description of Research
Our laboratory has had long-standing thematic interests in the cell-type and tissue-type specific actions of certain oncogenes (cyclin D1, Ki-Ras, EGFR) and tumor suppressor genes (p53, p16INK4a) in modulating the initiation, progression and invasion of gastrointestinal cancers, especially upper GI, pancreatic and colon. To that end, we employ novel three-dimensional cell culture systems (mouse and human origins) and geneticaly-engineered mouse models to investigate molecular mechanisms. These projects are translated into the objectives of improving molecular diagnostics and experimental therapeutics in patients.
Our research is funded through an NCI program project entitled "Mechanisms of Esophageal Carcinogenesis", NIH R01 grant on pancreatic cancer, and NIH R01 grant on colon cancer. Students and postdoctoral fellows are supported in didactic venues and conferences, present at national meetings, and have obtained national grant fellowships when applicable.
Rotation Projects for 2013-2014
1. To understand the role of oncogenes (EGFR, cyclin D1, Ras) and tumor suppressor genes (p53, p120catenin) in the tumor microenvironment as they relate to tumor cell migration and invasion in GI cancers, using organotypic culture and mouse models.
2. To define mechanisms underlying cell lineage during pancreatic development and cancer
3. To functionally characterize oncogenes in colon cancers.
4. To functionally characterize stem cells in the upper GI tract.
Basil Bakir, MD PhD student, CAMB (thesis project)
Koushik Das, MD, Gastroenterology fellow
Veronique Giroux, PhD, Postdoctoral Researcher (Canadian fellowship)
Kathryn Hamilton, PhD, Postdoctoral fellow (NIH F32 fellowship)
Steffen Heeg, MD, Postdoctoral Researcher (German Cancer Society fellowship)
Christopher Hahn, BA, Research Specialist
Arjun Jeganathan, MD, Gastroenterology Surgery Resident
Tatiana Karakasheva, PhD student, CAMB (thesis project)
Apple Long, MD PhD student, CAMB (PhD thesis project)
Emma Lundsmith, medical student (HHMI fellowship)
Blair Madison, PhD, Research Associate (NIH K01 grant)
Ben Rhoades, M.B., Research specialist and lab manager
Max Reichert, MD, Postdoctoral Researcher (National Pancreas Foundation fellowship)
Shigetsugu Takano, MD, Visiting Assistant Professor
Maria Vega, PhD student, CAMB (thesis project; NIH T32 training grant)
Todd Waldron, PhD, Postdoctoral fellow (NIH F32 fellowship)
Recently in Lab:
Daniel Abravanel, University of Pennsylvania, Rotating MD, PhD Student Claudia Andl, PhD, Research Associate (recipient of NIH K01 grant and AGA Research Scholar Award). Now faculty at Vanderbilt University.
Amy Demicco,University of Pennsylvania, Rotating PhD Student
Brent Fargnoli, University of Pennsylvania undergraduate student (University and Ben Franklin Scholar). Now medical student at University of Pennsylvania.
Christie Gutierrez, University of Pennsylvania, Undergraduate student (AGA student fellowship)
Katharine D. Grugan, PhD,Postdoctoral fellow (recipient of NIH F32 fellowship). Currently, at Centocor.
Cameron Johnstone, PhD, Research Investigator (recipient of American Association for Cancer Research fellowship and Department of Defense grant). Now at Peter McCallum Cancer Institute, Melbourne, Australia.
Elizabeth Kennedy, University of Pennsylvania, Rotating PhD student Catrina King, PhD Received her PhD in Dec 2010; graduate of VMD program. Now a resident at Columbia University Medical Center
Carmen Z. Michaylira, PhD, Postdoctoral fellow (recipient of NIH F32 fellowship)
Charles Miller, University of Pennsylvania, Undergraduate student
Perry Mongroo, PhD, Postdoctoral fellow
Keeley Mui, University of Pennsylvania, Rotating PhD Student
Anna-Sophie Rich, University of Pennsylvania, Medical Student (recipient of NIH/NIDDK fellowship)
Doug Stairs, PhD, Now Assistant Professor of Pathology, Hershey Medical Center (Recipient of NIH F32 fellowship and NIH K99-R00 grant in lab) Jonathan Toung, University of Pennsylvania, Undergraduate Student (Vagelos Scholar)
Johannes von Burstin, MD, Postdoctoral fellow (recipient of DFG fellowship). At Technical University, Munich, Germany.
Melanie P. Wescott, PhD, Postdoctoral fellow (recipient of National Pancreas Foundation fellowship)
Louise Wang, University of Pennsylvania, undergraduate student (NIH fellowship). Now medical student at Stanford University
Rafi Winograd, University of Pennsylvania Rotating MD PhD student
Gabrielle Wong, PhD student, CAMB (thesis project; NIH T32 training grant)
Bihui(Claudia) Xu, University of Pennsylvania Rotating PhD student
Yao Yao, University of Pennsylvania, Rotating DVM PhD Student
Opitz OG, Suliman Y, Hahn WC, Harada H, Blum HE, Rustgi AK: Cyclin D1 overexpression and p53 inactivation immortalize primary oral keratinocytes by a telomerase independent mechanism. Journal of Clinical Investigation 108: 725-732, 2001 Notes: Commentary in Journal of Clinical Investigation and Nature Cancer Reviews.
Opitz O.G., Harada H., Suliman Y., Rhoades B., Sharpless N.E., Kent R., Kopelovich L., Nakagawa H., Rustgi A.K.: A mouse genetic model of human oral-esophageal cancer. Journal of Clinical Investigation 110: 761-769, 2002.
Andl CD., Mizushima T., Nakagawa H., Oyama K., Harada H., Chruma K., Herlyn M., Rustgi AK.: Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo. Journal of Biological Chemistry 278(3): 1824-30, Jan 17 2003.
Deramaudt TB, Takaoka M, Upadhyay R, Bowser MJ, Porter J, Lee A, Rhoades B, Johnstone CN, Weissleder R, Hingorani SR, Mahmood U, Rustgi AK: N-cadherin and keratinocyte growth factor receptor mediate the functional interplay between Ki-RASG12V and p53V143A in promoting pancreatic cell migration, invasion, and tissue architecture disruption. Mol Cell Biol 26(11): 4185-4200, 2006.
Okawa, T., Michaylira, C.Z., Kalabis, J., Stair, D., Nakagawa, H., Andl, C., Claudia, D., Johnstone, C.N., Andres, J., Klein-Szanto, A.J., El-Deiry, W.S., Cukierman, E., Herlyn, M., Rustgi, A.K.: The functional interplay between EGFR overexpression, hTERT activation and p53 mutation in esophageal epithelial cells with activation of stromal fibroblasts induce tumor development, invasion and differentiation. Genes & Development 21: 2788-803, 2007.
Kalabis J, Oyama K, Okawa T, Nakagawa H, Michaylira CZ, Stairs DB, Figueiredo JL, Mahmood U, Diehl JA, Herlyn M, Rustgi AK.: A subpopulation of mouse esophageal basal cells has properties of stem cells with the capacity for self-renewal and lineage specification. J Clinical Investigation 118(12): 3860-9, 2008.
Stairs DB, Bayne LJ, Rhoades B, Vega ME, Waldron TJ, Kalabis J, Klein-Szanto A, Katz JP, Diehl JA, Reynolds AB, Vonderheide RH, Rustgi AK : Deletion of p120-catenin results in a tumor microenvironment with inflammation and cancer that establishes it as a tumor suppressor gene. Cancer Cell 19(4): 470-83, 2011.
Quante M, Bhagat G, Abrams JA, Marache F, Good P, Lee MD, Lee Y, Friedman R, Asfaha S, Dubeykovskaya Z, Mahmood U, Figueiredo JL, Kitajewski J, Shawber C, Lightdale CJ, Rustgi AK, Wang TC: Bile acid and inflammation activate gastric cardia stem cells in a mouse model of Barrett-like metaplasia. Cancer Cell 21(1): 36-51, 2012.
Kalabis J, Wong GS, Vega ME, Natsuizaka M, Robertson ES, Herlyn M, Nakagawa H, Rustgi AK. : Isolation and characterization of mouse and human esophageal epithelial cells in 3D organotypic culture. Nature Protocols 7(2): 235-46, 2012.
Reichert M, Takeano, S, von Burstin, J, Kim, SB, Lee, JS, Stansbury, KI, Hahn, C, Heeg, S, Schneider, G, Rhim, A, Stanger, BZ, Rustgi, AK: The Prrx1 homeodomain transcription factor plays a central role in pancreatic regeneration and carcinogenesis. Genes & Development 27: 288-300, 2013.
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Last updated: 04/02/2014
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