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Margie L. Clapper, PhD

Margie L. Clapper, PhD
About

Professor

Co-Leader, Cancer Prevention and Control Program

Adjunct Faculty, Lewis Katz School of Medicine, Temple University

Research Program

First report that the lung can metabolize estrogen extensively. Its conversion to 4-hydroxyestrogen, a putative carcinogen, is accelerated in mice exposed to tobacco smoke.
Early detection of colorectal tumors in Apc+/Min-FCCC mice using endoscopic examinations (panel A) and infrared bioactivatable probes specific for matrix metalloproteinases (panel B) has provided new insight into the growth characteristics of preneoplastic colorectal lesions.
The presence vs. loss of p53 drives the formation of polypoid and flat colitis-associated colorectal neoplasms, respectively. The morphological subtypes also vary in their response to therapeutic intervention; a critical factor for consideration during chemopreventive agent development.
Colorectal Adenomas in FCCC ApcMin/+ Mice
Colitis-associated Colorectal Neoplasia in Mice treated with AOM/DSS
Education, Training & Credentials

Educational Background

  • PhD, Genetics/Cell Biology, University of Connecticut at Storrs, CT, 1986
  • BS, Biology, State Univ. College of New York at Oneonta, NY, 1980

Memberships

  • NCI IRG Subcommittee A for Review of Cancer Centers
  • Prime Contractor, Division of Cancer Prevention, NCI
  • External Advisory Board, UCLA-Boston University SPORE in Lung Cancer

Honors & Awards

  • Alumni of Distinction, 125th Anniversary of the State University of New York, Oneonta, NY, 2014
Research Profile

Research Program

Research Interests

  • Genetic mechanisms underlying the development of spontaneous and colitis-associated colorectal cancer
  • Gene-environment interactions that contribute to racial and gender-based differences in lung cancer susceptibility
  • Characterization of promising cancer preventive agents and their mechanisms of action in tumor prone mouse models
  • Novel image-based strategies for the earliest detection of preneoplasia

Lab Overview

This program, initiated more than 20 years ago, is one of the first basic research programs nationally to focus on cancer prevention. Its overall goal is to develop novel, efficacious preventive regimens for individuals at high risk for cancer. Projects focus on the identification of early molecular alterations that may serve as biomarkers of cancer risk and targets for therapeutic intervention in colorectal and lung carcinogenesis. All research is highly translational, with experimentation spanning from cultured cells and genetically defined animal models to the analysis of human tissues. Application of state-of-the-art genomic and imaging technology to the analysis of well-defined mouse models continues to provide unique insight into the molecular basis of the carcinogenic process and potential strategies for tumor inhibition.

A major interest of the lab is to improve our ability to detect colorectal tumors early and establish regimens for the prevention of colorectal cancer in both subjects with known genetic risk and patients with inflammatory bowel disease. Scientific advances have been facilitated by the generation of a mouse strain (Apc+/Min-FCCC) that uniquely develops spontaneous colorectal tumors at a high multiplicity. This model has been used extensively to test agents for their cancer preventive activity and develop image-based probes for the detection of early neoplastic colorectal lesions. Analyses of the molecular mechanisms underlying colitis-associated neoplasia have led to the discovery that morphological subtypes of dysplasia arise via distinct genetic mechanisms and respond differently to therapeutic intervention.

The lab’s interest in hormones and lung cancer has led to the recent novel discovery that: 1) estrogen and its metabolites are present within murine and human lung tissue at detectable levels; 2) tobacco smoke induces the expression of estrogen-metabolism genes and the production of a putative carcinogen, 4-hydroxyestrogen, within the lung; and 3) estrogen metabolism varies with race among women. The group has extensively characterized the estrogen metabolizing capacity of human tissue from lung cancer patients and established an aerosol delivery facility to expose animals to environmental pollutants, including tobacco smoke and e-cigarette vapor, under tightly controlled conditions.

People

Jing Peng, PhD

Postdoctoral Associate

Room: P2161
215-214-3923

Lisa Vanderveer, BS

Scientific Associate

Room: P2161
215-214-3980

Arlene Wartenberg

Volunteer

Room: P2165
215-728-4302

Kristen Harvey, BS

Scientific Technician I

Debra Pohl

Administrative Assistant

Additional Staff

Mariana Fragoso, MS, Visiting Scientist, University Estadual Paulista, Botucatu Medical School, Brazil

Publications

Selected Publications

Salaün, M, Peng J, Hensley HH, Roder N, Flieder DB, Houlle-Crépin S, Abramovici-Roels O, Sabourin J-C, Thiberville L, Clapper ML. MMP-13 in-vivo molecular imaging reveals early expression in lung adenocarcinoma. PLoS One. 2015 Jul20;10(7):e0132960.  PubMed PMID: 26193700 [PubMed - in process]; PubMed Central PMCID: PMC4508003. PubMed

 

 

Chang WC, Zenser TV, Cooper HS, Clapper ML. Differential response of flat and polypoid colitis-associated colorectal neoplasias to chemopreventive agents and heterocyclic amines. Cancer Lett. 2013 Jun 28;334(1):62-8. PubMed PMID: 23415736; PubMed Central PMCID: PMC3770752. PubMed

 

 

Peng J, Xu X, Mace BE, Vanderveer LA, Workman LR, Slifker MJ, Sullivan PM, Veenstra TD, Clapper ML.  Estrogen metabolism within the lung and its modulation by tobacco smoke. Carcinogenesis. 2013 Apr;34(4):909-15. PubMed PMID: 23276798; PubMed Central PMCID: PMC3616670. PubMed

 

 

Clapper ML, Hensley HH, Chang W-C, Devarajan K, Nguyen MT, Cooper HS. Detection of colorectal adenomas using a bioactivatable probe specific for matrix metalloproteinase activity. Neoplasia. 2011 Aug;13(8):685-91. PubMed PMID: 21847360; PubMed Central PMCID: PMC3156659. PubMed

 

 

Shatalova EG, Klein-Szanto AJ, Devarajan K, Cukierman E, Clapper ML. Estrogen and cytochrome P450 1B1 contribute to both early- and late-stage head and neck carcinogenesis. Cancer Prev Res (Phila). 2011 Jan;4(1):107-15. PubMed PMID: 21205741; PubMed Central PMCID: PMC3043603. PubMed

 

 

Meireles SI, Esteves GH, Hirata R Jr, Peri S, Devarajan K, Slifker M, Mosier SL, Peng J, Vadhanam MV, Hurst HE, Neves EJ, Reis LF, Gairola CG, Gupta RC, Clapper ML.  Early changes in gene expression induced by tobacco smoke: Evidence for the importance of estrogen within lung tissue. Cancer Prev Res (Phila). 2010 Jun;3(6):707-17. PubMed PMID: 20515954; PubMed Central PMCID: PMC2896420. PubMed

 

 

Hensley HH, Merkel CE, Chang WC, Devarajan K, Cooper HS, Clapper ML. Endoscopic imaging and size estimation of colorectal adenomas in the multiple intestinal neoplasia mouse. Gastrointest Endosc. 2009 Mar;69(3 Pt 2):742-9. PubMed PMID: 19251020; PubMed Central PMCID: PMC2821747. PubMed

 

 

Egleston, BL, Meireles SI, Flieder DB, and Clapper ML.  Population-based trends in lung cancer incidence in women.  Seminars in Oncology. 2009 36: 506-515.  (Lead article in an edition devoted to lung cancer in women.) PubMed PMID: 19995642; PubMed Central PMCID: PMC2846780. PubMed

 

Clapper, ML, Gary MA, Coudry RA, Litwin S, Chang W-C L, Devarajan K, Lubet RA, Cooper HS.  5‑aminosalicylic acid inhibits colitis-associated colorectal dysplasias in the mouse model of azoxymethane/dextran sulfate sodium-induced colitis.  Inflamm. Bowel Dis. 2008 14:1341-1347. PubMed PMID: 18452197. PubMed

 

Cooper HS, Chang WC, Coudry R, Gary MA, Everley L, Spittle CS, Wang H, Litwin S, Clapper ML. Generation of a unique strain of multiple intestinal neoplasia (Apc+/Min-FCCC) mice with significantly increased numbers of colorectal adenomas. Mol Carcinog. 2005 Sep;44(1):31-41. PubMed PMID: 15937958. PubMed

 

Hensley HH, Chang WC, Clapper ML. Detection and volume determination of colonic tumors in Min mice by magnetic resonance micro-imaging. Magn Reson Med. 2004 PubMed

Additional Publications

My NCBI

This Fox Chase professor participates in the Undergraduate Summer Research Fellowship
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