Margaret M. Chou

faculty photo
Associate Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

Contact information
3615 Civic Center Boulevard
ARC Bldg, 816E
Philadelphia, PA 19104-6058
Office: 267-426-9228
Fax: 267-426-5165
Lab: 267-426-9229
Education:
B.A. (Biochemistry)
Barnard College (NY), 1987.
Res. Asst (Biochemistry/Cell Biology)
Rockefeller University (NY), 1989.
Ph.D. (Molecular Oncology)
Rockefeller University, 1993.
Post-doc (Cell Biology)
Harvard Medical School (MA), 1997.
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Description of Research Expertise

Research Interests
bone and soft tissue tumors
sarcoma
mechanisms of malignant transformation
ubiquitination
GTPases
NFkB

Description of Research
My career interest is to understand the mechanisms underlying malignant transformation. The progression of a normal cell into a cancerous one entails profound changes in numerous cellular functions, including its proliferation, survival, and motility/invasiveness, all of which contribute to metastatic behavior. These cell autonomous changes are coupled with alterations in the tumor cells’ microenvironment, which exhibits a mutual regulation with the tumor cells and impacts upon the above properties. My work has been aimed at identifying the signaling pathways that play pivotal roles in these processes.
Most recently, we have focused our efforts on elucidating critical pathogenic factors in the development of bone and soft tissue tumors (BSTTs). In comparison to carcinomas and hematological malignancies, much less is known about the etiology of BSTTs, some of which preferentially affect children. A subset of pediatric BSTTs are driven by pathognomonic chromosomal translocations, including Ewing sarcoma, alveolar rhabdomyosarcoma, and aneurysmal bone cyst. Studies in my laboratory are aimed at identifying the mechanisms by which they contribute in disease pathogenesis. We have recently determined that the TRE17/USP6 oncogene acts as a critical pathogenic agent across a number of BSTTs. TRE17 affects multiple aspects of tumor cell biology and simultaneously modulates the tumor microenvironment. The goals of my laboratory are to determine the molecular mechanisms by which TRE17 functions, to identify additional cellular pathways critical for BSTT pathogenesis, and to develop murine models of BSTTs to ultimately allow development of novel therapeutic strategies.
My laboratory also focuses on pathogenic mechanisms of Ewing sarcoma, alveolar rhabdomyosarcoma, and a newly described cancer, sinonasal sarcoma. Efforts are underway to identify the mechanism by which their respective pathognomonic translocations function in these cancers, and identifying novel sensitivities to cytotoxic agents.



Lab personnel:

Laura Quick (Research Specialist)
Robert Young (Research Specialist)
Ian Henrich (Graduate student)
Krista Bledsoe (Post-doctoral associate)

Selected Publications

Pringle L M, Young R, Quick L, Riquelme D N, Oliveira A M, May M J, Chou M M: Atypical mechanism of NF-κB activation by TRE17/ubiquitin-specific protease 6 (USP6) oncogene and its requirement in tumorigenesis. Oncogene 31(30): 3525-35, Jul 2012.

Oliveira Andre M, Chou Margaret M: The TRE17/USP6 oncogene: a riddle wrapped in a mystery inside an enigma. Frontiers in bioscience (Scholar edition) 4: 321-34, Jan 1 2012.

Erickson-Johnson Michele R, Chou Margaret M, Evers Barbara R, Roth Christopher W, Seys Amber R, Jin Long, Ye Ying, Lau Alan W, Wang Xiaoke, Oliveira Andre M: Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion. Laboratory investigation; a journal of technical methods and pathology 91(10): 1427-33, Oct 2011.

Pietschmann Matthias F, Oliveira Andre M, Chou Margaret M, Ihrler Stefan, Niederhagen Manuel, Baur-Melnyk Andrea, Dürr Hans Roland: Aneurysmal bone cysts of soft tissue represent true neoplasms: a report of two cases. The Journal of bone and joint surgery. American volume 93(9): e45, May 2011.

Lau Alan W, Pringle Lashon M, Quick Laura, Riquelme Daisy N, Ye Ying, Oliveira Andre M, Chou Margaret M: TRE17/ubiquitin-specific protease 6 (USP6) oncogene translocated in aneurysmal bone cyst blocks osteoblastic maturation via an autocrine mechanism involving bone morphogenetic protein dysregulation. The Journal of biological chemistry 285(47): 37111-20, Nov 2010.

Ye Y, Pringle LM, Lau AW, Riquelme DN, Wang H, Jiang T, Lev D, Welman A, Blobel GA, Oliveira AM, Chou MM.: TRE17/USP6 oncogene translocated in aneurysmal bone cyst induces matrix metalloproteinase production via activation of NF-kappaB. Oncogene In press, April 2010.

Blobel, G.A., Kadauke, S., Wang, E., Lau, A.W., Zuber, J., Chou, M.M., and Vakoc, C.R.: A reconfigured pattern of MLL occupancy within mitotic chromatin promotes rapid transcriptional reactivation following mitotic exit. Molecular Cell 36(6): 970-983, December 2009.

Fellig, Y., Oliveira, A.M., Margolin, E., Gomori, J.M., Erickson-Johnson, M.R., Chou, M.M., Umansky, F., and Soffer, D.: Extraosseous aneurysmal bone cyst of cerebello-pontine angle with USP6 rearrangement. Acta Neuropathology 118: 579-581, Sept 2009.

Lau, AW and Chou, MM.: The adaptor complex AP-2 regulates post-endocytic trafficking through the non-clathrin Arf6-dependent endocytic pathway. Journal of Cell Science 121(24): 4008-4017, Nov 2008.

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Last updated: 03/15/2021
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