Margaret M. Chou, PhD
Associate Professor of Pathology and Laboratory Medicine
Associate Professor of Cell and Developmental Biology
Perelman School of Medicine at the University of Pennsylvania
Contact Information3615 Civic Center Boulevard
ARC Bldg, 816E
Philadelphia, PA, 19104-6058
Office: 267-426-9228
Fax: 267-426-5165
Email: mmc@pennmedicine.upenn.edu
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)
Itmat Expertise
Pediatric neoplasms
Sarcoma
Inflammatory signaling
Ubiquitination
GTPases
Graduate Groups
Cell and Molecular Biology
Pharmacology
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
Specialty Certification
Postgraduate Training
Research Assistant, Rockefeller University (Biochemistry/CellBiology), 1987-1989
Post-doctoral Fellow, Harvard Medical School/Dept. of Cell Biology, 1993-1977
Awards and Honors
Leukemia and Lymphoma Society, Research Special Fellow,
Memberships and Professional Organizations
AACR, 2013 - Current
Society for Immunotherapy in Cancer, 2017 - current
NCI Study Section
Special Emphasis Panel: OBT Cancer Biology
Ad hoc Member, 2017 - 2017
NCI Study Section
Special Emphasis Panel: Provocative Questions in Pediatric Cancer
Ad Hoc Member, 2018 - 2018
Member of Membrane Biology and Protein Processing (MBPP) Study
Section, NIH, - Present
American Society for Cell Biology, - Present
American Society for Microbiology, - Present
Web Links
Pharmacological Sciences graduate group faculty webpage.
Selected Publications
Atypical mechanism of NF-κB activation by TRE17/ubiquitin-specific protease 6 (USP6) oncogene and its requirement in tumorigenesis.
Pringle L M, Young R, Quick L, Riquelme D N, Oliveira A M, May M J, Chou M M, Oncogene 31(30): 3525-35, 2012, PMID:22081069
The TRE17/USP6 oncogene: a riddle wrapped in a mystery inside an enigma.
Oliveira Andre M, Chou Margaret M, Frontiers in bioscience (Scholar edition) 4(): 321-34, 2012, PMID:22202063
Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion.
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, Laboratory investigation; a journal of technical methods and pathology 91(10): 1427-33, 2011, PMID:21826056
Aneurysmal bone cysts of soft tissue represent true neoplasms: a report of two cases.
Pietschmann Matthias F, Oliveira Andre M, Chou Margaret M, Ihrler Stefan, Niederhagen Manuel, Baur-Melnyk Andrea, Dürr Hans Roland, The Journal of bone and joint surgery. American volume 93(9): e45, 2011, PMID:21543666
TRE17/ubiquitin-specific protease 6 (USP6) oncogene translocated in aneurysmal bone cyst blocks osteoblastic maturation via an autocrine mechanism involving bone morphogenetic protein dysregulation.
Lau Alan W, Pringle Lashon M, Quick Laura, Riquelme Daisy N, Ye Ying, Oliveira Andre M, Chou Margaret M, The Journal of biological chemistry 285(47): 37111-20, 2010, PMID:20864534
TRE17/USP6 oncogene translocated in aneurysmal bone cyst induces matrix metalloproteinase production via activation of NF-kappaB
Ye Y, Pringle LM, Lau AW, Riquelme DN, Wang H, Jiang T, Lev D, Welman A, Blobel GA, Oliveira AM, Chou MM., Oncogene In press(): , 2010, PMID:20418905
A reconfigured pattern of MLL occupancy within mitotic chromatin promotes rapid transcriptional reactivation following mitotic exit
Blobel, G.A., Kadauke, S., Wang, E., Lau, A.W., Zuber, J., Chou, M.M., and Vakoc, C.R., Molecular Cell 36(6): 970-983, 2009
Extraosseous aneurysmal bone cyst of cerebello-pontine angle with USP6 rearrangement
Fellig, Y., Oliveira, A.M., Margolin, E., Gomori, J.M., Erickson-Johnson, M.R., Chou, M.M., Umansky, F., and Soffer, D., Acta Neuropathology 118(): 579-581, 2009, PMID:19690876
The adaptor complex AP-2 regulates post-endocytic trafficking through the non-clathrin Arf6-dependent endocytic pathway.
Lau, AW and Chou, MM., Journal of Cell Science 121(24): 4008-4017, 2008, PMID:19033387
