Isabelle Mercier PhD

Isabelle Mercier, PhD

Isabelle Mercier PhD

Associate Professor of Pharmaceutical Sciences

Education

BS, University of Montreal (Montreal, Canada), Biochemistry, 1995-1998

PhD, University of Montreal (Montreal, Canada), Physiology, 1998-2004

Research Interests

Breast and prostate cancers continue to be the most commonly diagnosed cancers among Americans. My laboratory focuses on the characterization and molecular targeting of key proteins involved in breast and prostate tumorigenesis, using both in vitro cell culture and clinically relevant in vivo models.

Most breast and prostate cancers are initially dependent on the presence of hormones through the estrogen and androgen receptors. The most effective treatments are estrogen blockade with tamoxifen for breast cancer or androgen deprivation therapy (ADT) in the form of pharmacological or surgical castration for prostate cancer. Although initially responsive, several patients under these therapies inevitably relapse with a more aggressive form of cancer termed "refractory cancers" leading inevitably to death. Unfortunately, the mechanisms responsible for these aggressive cancers remain mostly unknown and are the limiting step in curing breast and prostate cancers.

Our research focuses on finding more effective biomarkers and therapeutic targets to ameliorate the clinical outcome of these patients by preventing their transition to hormone-refractory cancers. We are mainly focusing on the specific targeting of novel proteins involved in tumor metabolism, tumor microenvironment and aging that could be responsible for the development of these advanced cancers. Our research team recently identified metabolic and aging pathways that can be targeted pharmacologically in the tumor microenvironment to prevent tumor growth significantly.

These important findings might open up new treatment formulations, delivery and stratification in patients in a very near future.

Synopsis

Breast and prostate cancers continue to be the most commonly diagnosed cancers among Americans. My laboratory focuses on the characterization and molecular targeting of key proteins involved in breast and prostate tumorigenesis, using both in vitro cell culture and clinically relevant in vivo models.

Selected Scholarly Activity

Publications

Quann K, Gonzales DM, Mercier I, Wang C, Sotgia F, Lisanti MP, Jasmin JF. “Caveolin-1 is a Negative Regulator of Tumor Growth in Glioblastoma and Modulates Chemosensitivity to Temozolomide.” Cell Cycle. 2013; 12 (10): 1510-20.

Mercier I, Camacho J, Titchen K, Gonzales DM, Quann K, Bryant KG, Molchansky A, Milliman J, Whitaker-Menezes D, Sotgia F, Jasmin JF, Schwarting R, Pestell RG, Blagosklonny MV , and Lisanti MP. “Caveolin-1 and Accelerated Host Aging in the Breast Tumor Microenvironment: Chemoprevention with Rapamycin, an mTOR Inhibitor and Anti-Aging Drug." American Journal of Pathol. 2012; 181(1): 278-293.

Bryant KG, Camacho J, Jasmin JF, Wang C, Addya S, Casimiro MC, Fortina P, Balasubramaniam S, Knudsen KE, Schwarting R, Lisanti MP, Mercier I. “Caveolin-1 overexpression enhances androgen-dependent growth and proliferation in the mouse prostate." Int J Biochem Cell Biol. 2011 Sep;43(9):1318-29.

Jasmin JF, Rengo G, Lymperopoulos A, Gupta R, Eaton GJ, Quann K, Gonzales DM, Mercier I, Koch WJ, Lisanti MP. "Caveolin-1 deficiency exacerbates cardiac dysfunction and reduces survival in mice with myocardial infarction." Am J Physiol Heart Circ Physiol. 2011; 300 (4): H1274-81.

Llaverias G, Danilo C, Mercier I, Daumer K, Capozza F, Williams TM, Sotgia F, Lisanti MP, Frank PG. "Role of Cholesterol in the Development and Progression of Breast Cancer." Am J Pathol. 2011; 178 (1): 402-412.

Martinez-Outschoorn UE, Whitaker-Menezes D, Pavlides S, Chiavarina B, Bonuccelli G, Trimmer C, Tsirigos A, Migneco G, Witkiewicz AK, Balliet R, Mercier I, Wang C, Flomenberg N, Howell A, Lin Z, Caro J, Pestell RG, Sotgia F, Lisanti MP. The autophagic tumor stroma model of cancer or "battery-operated tumor growth": A simple solution to the autophagy paradox. Cell Cycle. 2010; 9 (21): 4297-306.

Mercier I., Casimiro M.C., Zhou J., Wang C., Plymire C., Bryant K.G., Daumer K.M., Sotgia F., Bonuccelli G., Witkiewicz A.K., Lin J., Tran T.H., Milliman J., Frank P.G., Jasmin J.F., Rui H., Pestell R.G., Lisanti M.P. 2008. "Genetic Ablation of Caveolin-1 Drives Estrogen-Hypersensitivity and the Development of DCIS-like Mammary Lesions." Am. J. Pathol. 2009; 174 (4): 1172-90.

Mercier I., Bryant K.G., Sotgia F., Bonuccelli G., Witkiewicz A.K., Dasgupta A., Jasmin J.F., Pestell R.G., Lisanti M.P. "Using Caveolin-1 Epithelial Immunostaining Patterns to Stratify Human Breast Cancer Patients and to Predict the Caveolin-1 (P132L) Mutation." Cell cycle. 2009; 8 (9): 1396-401.

Sotgia F., Del Galdo F., Casimiro M.C., Bonuccelli G., Mercier I., Whitaker-Menezes D., Daumer K., Zhou J., Wang C., Katiyar S., Xu H., Bosco E., Quong A., Aronow B., Witkiewicz A.K., Minetti C., Frank P., Jimenez S., Knudsen E.S., Pestell R.G., Lisanti M.P. "Caveolin-1 (-/-) Null Mammary Stromal Fibroblasts Share Characteristics with Human Breast Cancer-Associated Fibroblasts." Am. J. Pathol. 2009; 174 (3): 746-61.

Sotgia F., Casimiro M.C., Bonuccelli G., Liu M., Whitaker-Menezes D., Er O., Daumer K., Mercier I., Witkiewicz A.K., Minetti C., Capozza F., Gormley M., Quong A., Rui H., Frank P., Milliman J., Knudsen E.S., Zhou J., Wang C., Pestell R.G., Lisanti M.P. "Loss of Caveolin-3 Induces a Lactogenic Microenvironment that is Protective Against Mammary Tumor Formation. Am. J. Pathol." 2009; 174 (2): 613-29

Bonuccelli G., Casimiro M.C., Sotgia F., Wang C., Liu M., Katiyar S., Zhou J., Dew E., Capozza F., Daumer K., Minetti C., Alpy F., Rio M.-C., Tomasetto C., Mercier I., Frank P.G., Pestell R.G., Lisanti M.P., 2009. "Caveolin-1 (P132L), A Common Breast Cancer Mutation, Confers Mammary Cell Invasiveness and Defines a Novel Stem Cell/Metastasis-Associated Gene Signature." Am. J. Pathol. 2009; 174 (5): 1650-62.

Witkiewicz A.K., Dasgupta A., Sotgia F., Mercier I., Pestell R.G., Sabel M., Kleer C., Brody J.R., Lisanti M.P. "An Absence of Stromal Caveolin-1 Expression Predicts Early Tumor Recurrence and Poor Clinical Outcome in Human Breast Cancers." Am. J. Pathol. 2009; 174 (6): 2023-2034.

Mercier, I., Vuolo, M., Jasmin, J.F., Medina, C.M., Williams, M., Mariadason, J.M., Qian, H., Xue, X., Pestell, R.G., Lisanti, M.P., and Kitsis, R.N. 2008. "ARC (apoptosis repressor with caspase recruitment domain) is a novel marker of human colon cancer." Cell Cycle, 2008; 7(11):1640-1647.

Mercier, I., Casimiro, M.C., Wang, C., Rosenberg, A.L., Quong, J., Allen, K.G., Danilo, C., Sotgia, F., Bonnucelli , G., Jasmin , J.F., Xu, H., Bosco, E., Aronow, B., Witkiewicz, A., Pestell , R.G., Knudsen , E.S., Lisanti, M.P. 2008. "Human Breast Cancer-Associated Fibroblasts (CAFs) Show Caveolin-1 Down-regulation and RB Tumor Suppressor Functional Inactivation: Implications for the Response to Hormonal Therapy." Cancer Biology & Therapy, 2008; 7(8): 1212-1225.

Jasmin J.F., Malhotra S., Dhallu M.S., Mercier I., Rosenbaum D.M., Lisanti M.P. "Caveolin-1 deficiency increases cerebral ischemic injury." Circ Res. 2007; 100(5): 721-729.

Williams T.M., Sotgia F., Lee H., Hassan G., Di Vizio D., Bonuccelli G., Capozza F., Mercier I., Rui H., Pestell R.G., Lisanti M.P. "Stromal and epithelial caveolin-1 both confer a protective effect against mammary hyperplasia and tumorigenesis: Caveolin-1 antagonizes cyclin D1 function in mammary epithelial cells." Am J Pathol. 2006, 169(5): 1784-1801.

Jasmin J.F., Mercier I., Dupuis J., Tanowitz H.B., Lisanti M.P. "Short term administration of a cell-permeable caveolin-1 peptide prevents the development of monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy." Circulation. 2006; 114(9): 912-920.

Mercier I., Vuolo M., Madan R., Xue X., Levalley A.J., Ashton A.W., Jasmin J.F., Czaja M.T., Lin E.Y., Armstrong R.C., Pollard J.W., Kitsis R.N. ARC, an apoptosis suppressor limited to terminally differentiated cells, is induced in human breast cancer and confers chemo- and radiation-resistance. Cell Death Differ. 2005; 12(6): 682-6.

Jasmin J.F., Mercier I., Hnasko R., Cheung M.W., Tanowitz H.B., Dupuis J., Lisanti M.P. "Lung remodeling and pulmonary hypertension after myocardial infarction: pathogenic role of reduced caveolin expression." Cardiovasc Res. 2004; 63(4): 747-55.

Pham-Dang M., Clement R., Mercier I., Calderone A. "Comparative effects of tamoxifen and angiotensin II type-1 receptor antagonist therapy on the hemodynamic profile of the ovariectomized female rat." Can J Physiol Pharmacol. 2003; 81(9): 915-9.

Thorin E., Pham-Dang M., Clement R., Mercier I, Calderone A. "Hyper-reactivity of cerebral arteries from ovariectomized rats: therapeutic benefit of tamoxifen." Br J Pharmacol. 2003; 140(7): 1187-92.

Mercier I., Mader S., Calderone A. "Tamoxifen and ICI 182,780 negatively influenced cardiac cell growth via an estrogen receptor-independent mechanism." Cardiovasc Res. 2003; 59(4): 883-92.

Mercier I., Pham-Dang M., Clement R., Gosselin H., Colombo F., Rouleau J.L., Calderone A. "Elevated mean arterial pressure in the ovariectomized rat was normalized by ET(A) receptor antagonist therapy: absence of cardiac hypertrophy and fibrosis." Br J Pharmacol. 2002; 136(5): 685-92.

Sanchez R., MacKenzie A., Farhat N., Nguyen T.D., Stewart D.J., Mercier I., Calderone A., Thorin E. "Endothelin B receptor-mediated regulation of endothelin-1 content and release in cultured porcine aorta endothelial cell." J Cardiovasc Pharmacol. 2002; 39(5): 652-9.

Mercier I., Colombo F., Mader S., Calderone A. "Ovarian hormones induce TGF-beta(3) and fibronectin mRNAs but exhibit a disparate action on cardiac fibroblast proliferation." Cardiovasc Res. 2002; 53(3): 728-39.

Abdelaziz N., Colombo F., Mercier I., Calderone A. "Nitric oxide attenuates the expression of transforming growth factor-beta(3) mRNA in rat cardiac fibroblasts via destabilization." Hypertension. 2001; 38(2): 261-6.

Colombo F., Noel J., Mayers P., Mercier I., Calderone A. "beta-Adrenergic stimulation of rat cardiac fibroblasts promotes protein synthesis via the activation of phosphatidylinositol 3-kinase." J Mol Cell Cardiol. 2001; 33(6): 1091-106.

Eng F.C., Barsalou A., Akutsu N., Mercier I., Zechel C., Mader S., White J.H. "Different classes of coactivators recognize distinct but overlapping binding sites on the estrogen receptor ligand binding domain." J Biol Chem. 1998; 273(43): 28371-7.

Review Articles

Witkiewicz AK, Casimiro MC, Dasgupta A, Mercier I, Wang C, Bonuccelli G, Jasmin JF, Frank PG, Pestell RG, Kleer CG, Sotgia F, Lisanti MP. "Towards a new "stromal-based" classification system for human breast cancer prognosis and therapy." Cell Cycle. 2009; 8(11): 1654-8

Mercier I., Jasmin J.F., Pavlides S., Minetti C., Pestell R.G., Frank P., Sotgia F., Lisanti M.P. "Clinical and Translational Implications for the Caveolin Gene Family: Lessons from Mouse Models and Human Genetic Disorders." Lab Invest. 2009; 89 (6): 614-23.

Sotgia F., Rui H., Bonuccelli G., Mercier I., Pestell R.G., Lisanti M.P. "Caveolin-1, mammary stem cells, and estrogen-dependent breast cancers." Cancer Res. 2006, 66(22): 10647-10651.

Jasmin J.F., Mercier I., Sotgia F., Lisanti M.P. "SOCS proteins and caveolin-1 as negative regulators of endocrine signaling." Trends in Endocrinology and Metabolism. 2006; 17(4): 150-158.

Book Chapters

Mercier I and Lisanti MP. "Caveolin-1 and Breast Cancer: a New Clinical Perpective. Caveolins and Caveolae: Roles in Signaling and Disease Mechanisms (Landes Bioscience)." Edited by Jasmin JF, Frank PG and Lisanti MP. Adv Exp Med Biol. 2012; 729:83-94.

Mercier I and Lisanti M.P. "Caveolin-1 and Cancer-Associated Fibroblasts; Caveolin Proteins in Cancer Pathogenesis, Prevention and Therapy." Edited by Mercier I, Jasmin JF and Lisanti MP. Current Cancer Research. 2011. Springer.

Book Editing

Caveolin Proteins in Cancer Pathogenesis, Prevention and Therapy. Book edited by Mercier I, Jasmin JF, Lisanti MP. 2012: (http://www.springer.com/biomed/cancer/book/978-1-4614-1000-3). Springer Science.

Contact Information

Mailing address: University of Sciences
600 South 43rd Street
Philadelphia, PA 19104-4495
Office Phone: 215-596-7151
Email:

i [dot] mercier [at] usciences [dot] edu