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Biosketch / Results /

Pamela Cowin, Ph.D.

Professor;
Departments of Dermatology [1] and Cell Biology (Cell Biology) [2]

Contact Info

Address
550 First Avenue
Floor 6 Room 621
Medical Science Building
New York, NY 10016

212-263-6915, 212-263-8715
212-263-8139
Pamela.Cowin@nyumc.org


[4]

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Education

1984 — Dr. Cowin received her Ph.D. degree in Cell Adhesion from Southampton University, U.K., Graduate Education
1984-1987 — Dr. Cowin was a Postdoctoral Fellow in Cytoskeleton studies at the German Cancer Research Center, PostDoctoral Training

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Research Summary

Embryonic Patterning Pathways in Mammary Development and Breast Cancer

Mammary glands form in the embryo but also undergo extensive postnatal ductal development during puberty. Each pregnancy induces further cyclical rounds of proliferation and differentiation in preparation for lactation followed by apoptosis, and extensive remodeling after weaning. Mammary development is regulated temporarily by hormones but spatially by hormonally-induced localized paracrine factors. We study the roles of Wnt/beta-catenin and Hedgehog/Gli pathways in this process.

Beta-catenin is a multifunctional protein involved in cadherin-mediated cell adhesion at the plasma membrane and transcriptional regulation in the nucleus. Cadherin-catenin complexes are essential for maintaining epithelial integrity in the developing mammary gland. Their loss or transient downregulation occurs frequently in human breast cancer and facilitates invasion and metastasis. Numerous signaling pathways regulate the stability of cytosolic beta-catenin, the best understood being the canonical Wnt pathway. Wnts signal by stabilizing cytosolic beta-catenin and promoting its nuclear entry and transcriptional function. Wnt/beta-catenin signaling regulates normal mammary stem cell dynamics and is thus essential for many different stages of embryonic and postnatal mammary development. Our work has shown that deregulated I?-catenin signaling leads to mammary stem and progenitor cell accumulation, precocious development and breast cancer in mice. Recent studies suggest that a similar link exists between reactivation of developmental pathways and human breast cancer. Elevated beta-catenin signaling is particularly prevalent in metaplastic and basal subtypes of breast cancer, which have the worst prognosis and patient outcome. Deregulated beta-catenin signaling can occur by other signaling routes, and importantly many of these pathways are aberrant in breast cancer and when disturbed also cause mammary developmental abnormalities.

In addition we study the role of the Hedgehog/Gli pathway in the mammary gland and our work has shown that repression of Hedgehog signaling is critical for normal embryonic mammary development. Misactivation of this pathway in the embryo leads to loss of mammary buds. Currently we are studying the effects of derepressing this pathway during adult mammary development and our studies have shown that this event is critical for Wnt tumor induction.

Research Interests

Cell Adhesion and Wnt Signaling

Research Keywords

plakoglobin, catenins, Wnt signal transduction, oncogene, cell adhesion, mammary gland, epidermis

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All data from NYU Health Sciences Library Faculty Bibliography — -

Contact:
http://hsl.med.nyu.edu/faculty-bibliography-search [9]

A Systematic Screen for Micro-RNAs Regulating the Canonical Wnt Pathway
Anton, Roman; Chatterjee, Sujash S; Simundza, Julia; Cowin, Pamela; Dasgupta, Ramanuj
2011 ;6(10):e26257-e26257, PLoS ONE
— id: 140537, year: 2011, vol: 6, page: e26257, stat: Journal Article,

Choreographing Metastasis to the Tune of LTBP
Chandramouli, Anupama; Simundza, Julia; Pinderhughes, Alicia; Cowin, Pamela
2011 Jun;16(2):67-80, Journal of mammary gland biology & neoplasia
— id: 132580, year: 2011, vol: 16, page: 67, stat: Journal Article,

A mouse transgenic approach to induce beta-catenin signaling in a temporally controlled manner
Mukherjee, Atish; Soyal, Selma M; Li, Jie; Ying, Yan; Szwarc, Maria M; He, Bin; Kommagani, Ramakrishna; Hodgson, Myles C; Hiremath, Minoti; Cowin, Pamela; Lydon, John P
2011 Aug;20(4):827-840, Transgenic research
— id: 138283, year: 2011, vol: 20, page: 827, stat: Journal Article,

Distinct function of androgen receptor coactivator ARA70alpha and ARA70beta in mammary gland development, and in breast cancer
Wu, Xinyu; Chen, Fei; Sahin, Aysegul; Albarracin, Constance; Pei, Zhiheng; Zou, Xuanyi; Singh, Baljit; Xu, Ruliang; Daniels, Garrett; Li, Yirong; Wei, Jianjun; Blake, Marvin; Schneider, Robert J; Cowin, Pamela; Lee, Peng
2011 Jul;128(2):391-400, Breast cancer research & treatment
— id: 138162, year: 2011, vol: 128, page: 391, stat: Journal Article,

Molecular mechanisms guiding embryonic mammary gland development
Cowin, Pamela; Wysolmerski, John
2010 Jun 1;2(6):a003251-a003251, Cold Spring Harbor perspectives in biology
— id: 109851, year: 2010, vol: 2, page: a003251, stat: Journal Article,

Key signaling nodes in mammary gland development and cancer: beta-catenin
Incassati, Angela; Chandramouli, Anupama; Eelkema, Rachel; Cowin, Pamela
2010 ;12(6):213-213, Breast cancer research
— id: 138282, year: 2010, vol: 12, page: 213, stat: Journal Article,

Links between transforming growth factor-beta and canonical Wnt signaling yield new insights into breast cancer susceptibility, suppression and tumor heterogeneity
Incassati, Angela; Pinderhughes, Alicia; Eelkema, Rachel; Cowin, Pamela
2009 ;11(3):103-103, Breast cancer research
— id: 101284, year: 2009, vol: 11, page: 103, stat: Journal Article,

MMTV-Wnt1 and -DeltaN89beta-catenin induce canonical signaling in distinct progenitors and differentially activate Hedgehog signaling within mammary tumors
Teissedre, Brigitte; Pinderhughes, Alicia; Incassati, Angela; Hatsell, Sarah J; Hiremath, Minoti; Cowin, Pamela
2009 ;4(2):e4537-e4537, PLoS ONE
— id: 96250, year: 2009, vol: 4, page: e4537, stat: Journal Article,

Plakoglobin is required for effective intermediate filament anchorage to desmosomes
Acehan, Devrim; Petzold, Christopher; Gumper, Iwona; Sabatini, David D; Muller, Eliane J; Cowin, Pamela; Stokes, David L
2008 Nov;128(11):2665-2675, Journal of investigative dermatology
— id: 93304, year: 2008, vol: 128, page: 2665, stat: Journal Article,

Breast cancer progression: controversies and consensus in the molecular mechanisms of metastasis and EMT
Cowin, Pamela; Welch, Danny R
2007 Sep;12(2-3):99-102, Journal of mammary gland biology & neoplasia
— id: 91971, year: 2007, vol: 12, page: 99, stat: Journal Article,

The pattern of beta-catenin responsiveness within the mammary gland is regulated by progesterone receptor
Hiremath, Minoti; Lydon, John P; Cowin, Pamela
2007 Oct;134(20):3703-3712, Development
— id: 76076, year: 2007, vol: 134, page: 3703, stat: Journal Article,

Gli3-mediated repression of Hedgehog targets is required for normal mammary development
Hatsell, Sarah J; Cowin, Pamela
2006 Sep;133(18):3661-3670, Development
— id: 69584, year: 2006, vol: 133, page: 3661, stat: Journal Article,

Cadherins and catenins in breast cancer
Cowin, Pamela; Rowlands, Tracey M; Hatsell, Sarah J
2005 Oct;17(5):499-508, Current opinion in cell biology
— id: 96251, year: 2005, vol: 17, page: 499, stat: Journal Article,

Beta-catenin induces a population of radio-resistant alveolar stem/progenitors that progress to form hormone-independent breast tumors in mice
Formenti, SC; Hiremath, M; Yang, A; Demaria, S; Cowin, P
2005 ;63(2):2396-2396, International journal of radiation oncology biology physics
— id: 109265, year: 2005, vol: 63, page: 2396, stat: Journal Article,

Bone morphogenetic protein signaling regulates postnatal hair follicle differentiation and cycling
Guha, Udayan; Mecklenburg, Lars; Cowin, Pamela; Kan, Lixin; O'Guin, W Michael; D'Vizio, Dolores; Pestell, Richard G; Paus, Ralf; Kessler, John A
2004 Sep;165(3):729-740, American journal of pathology
— id: 44783, year: 2004, vol: 165, page: 729, stat: Journal Article,

Beta-catenin and Cyclin D1: Connecting Development to Breast Cancer
Rowlands, Tracey M; Pechenkina, Irina V; Hatsell, Sarah; Cowin, Pamela
2004 Mar-Apr;3(2):145-148, Cell cycle
— id: 41643, year: 2004, vol: 3, page: 145, stat: Journal Article,

Plakoglobin is O-glycosylated close to the N-terminal destruction box
Hatsell, Sarah; Medina, Lillian; Merola, Joe; Haltiwanger, Robert; Cowin, Pamela
2003 Sep 26;278(39):37745-37752, Journal of biological chemistry
— id: 38123, year: 2003, vol: 278, page: 37745, stat: Journal Article,

Beta-catenin and Tcfs in mammary development and cancer
Hatsell, Sarah; Rowlands, Tracey; Hiremath, Minoti; Cowin, Pamela
2003 Apr;8(2):145-158, Journal of mammary gland biology & neoplasia
— id: 44866, year: 2003, vol: 8, page: 145, stat: Journal Article,

Untangling desmosomal knots with electron tomography
He, Wanzhong; Cowin, Pamela; Stokes, David L
2003 Oct 3;302(5642):109-113, Science
— id: 38124, year: 2003, vol: 302, page: 109, stat: Journal Article,

Evidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells
Li, Yi; Welm, Bryan; Podsypanina, Katrina; Huang, Shixia; Chamorro, Mario; Zhang, Xiaomei; Rowlands, Tracey; Egeblad, Mikala; Cowin, Pam; Werb, Zena; Tan, Lee K; Rosen, Jeffrey M; Varmus, Harold E
2003 Dec 23;100(26):15853-15858, Proceedings of the National Academy of Sciences of the United States of America
— id: 41642, year: 2003, vol: 100, page: 15853, stat: Journal Article,

Mammary gland development requires syndecan-1 to create a beta-catenin/TCF-responsive mammary epithelial subpopulation
Liu, Bob Y; Kim, Young Chul; Leatherberry, Vicki; Cowin, Pam; Alexander, Caroline M
2003 Dec 18;22(58):9243-9253, Oncogene
— id: 41641, year: 2003, vol: 22, page: 9243, stat: Journal Article,

Molecular cloning of the mouse Ltbp-1 gene reveals tissue specific expression of alternatively spliced forms
Noguera, Irene; Obata, Hiroto; Gualandris, Anna; Cowin, Pamela; Rifkin, Daniel B
2003 Apr 10;308(5642):31-41, Gene
— id: 38125, year: 2003, vol: 308, page: 31, stat: Journal Article,

Dissecting the roles of beta-catenin and cyclin D1 during mammary development and neoplasia
Rowlands, Tracey M; Pechenkina, Irina V; Hatsell, Sarah J; Pestell, Richard G; Cowin, Pamela
2003 Sep 30;100(20):11400-11405, Proceedings of the National Academy of Sciences of the United States of America
— id: 38126, year: 2003, vol: 100, page: 11400, stat: Journal Article,

Going undercover
Cowin P; Sun TT
2001 ;107:287-289, Cell
— id: 32401, year: 2001, vol: 107, page: 287, stat: Journal Article,

Deconstructing desmoplakin
Hatsell, S; Cowin, P
2001 DEC ;3(12):E270-E272, Nature cell biology
— id: 54788, year: 2001, vol: 3, page: E270, stat: Journal Article,

Delta N89 beta-catenin induces precocious development, differentiation, and neoplasia in mammary gland
Imbert A; Eelkema R; Jordan S; Feiner H; Cowin P
2001 Apr 30;153(3):555-568, Journal of cell biology
— id: 20693, year: 2001, vol: 153, page: 555, stat: Journal Article,

Appearance of Langerhans cells in the epidermis of Tgfb1(-/-) SCID mice: paracrine and autocrine effects of transforming growth factor-beta 1 and -beta 2(1)
Thomas RM; Belsito DV; Huang C; Chen Lz LZ; Ormsby I; Simmons WJ; Cowin P; Shaw J; Doetschman T; Thorbecke GJ
2001 Dec;117(6):1574-1580, Journal of investigative dermatology
— id: 32235, year: 2001, vol: 117, page: 1574, stat: Journal Article,

Plakoglobin suppresses epithelial proliferation and hair growth in vivo
Charpentier E; Lavker RM; Acquista E; Cowin P
2000 Apr 17;149(2):503-520, Journal of cell biology
— id: 11747, year: 2000, vol: 149, page: 503, stat: Journal Article,

Cytoskeletal-membrane interactions and signal transduction
Cowin, Pam; Klymkowsky, Michael
New York : Chapman & Hall ; Austin, Tex. : Landes Bioscience, c1997,
— id: 576, year: 1997, vol: , page: , stat: ,

Cytoskeleton-membrane interactions [published erratum appears in Curr Opin Cell Biol 1996 Apr;8(2):following 244]
Cowin P; Burke B
1996 Feb;8(1):56-65, Current opinion in cell biology
— id: 6896, year: 1996, vol: 8, page: 56, stat: Journal Article,

Desmosomal cadherin binding domains of plakoglobin
Witcher LL; Collins R; Puttagunta S; Mechanic SE; Munson M; Gumbiner B; Cowin P
1996 May 3;271(18):10904-10909, Journal of biological chemistry
— id: 7059, year: 1996, vol: 271, page: 10904, stat: Journal Article,

Protein zero, a nervous system adhesion molecule, triggers epithelial reversion in host carcinoma cells
Doyle JP; Stempak JG; Cowin P; Colman DR; D'Urso D
1995 Oct;131(2):465-482, Journal of cell biology
— id: 16330, year: 1995, vol: 131, page: 465, stat: Journal Article,

Unraveling the cytoplasmic interactions of the cadherin superfamily [see comments]
Cowin P
1994 Nov 8;91(23):10759-10761, Proceedings of the National Academy of Sciences of the United States of America
— id: 6598, year: 1994, vol: 91, page: 10759, stat: Journal Article,

Interactions of the cytoplasmic domain of the desmosomal cadherin Dsg1 with plakoglobin
Mathur M; Goodwin L; Cowin P
1994 May 13;269(19):14075-14080, Journal of biological chemistry
— id: 6448, year: 1994, vol: 269, page: 14075, stat: Journal Article,

Structure of DSG1, the bovine desmosomal cadherin gene encoding the pemphigus foliaceus antigen. Evidence of polymorphism
Puttagunta S; Mathur M; Cowin P
1994 Jan 21;269(3):1949-1955, Journal of biological chemistry
— id: 6489, year: 1994, vol: 269, page: 1949, stat: Journal Article,

Alterations in beta-catenin phosphorylation and plakoglobin expression in human breast cancer cells
Sommers CL; Gelmann EP; Kemler R; Cowin P; Byers SW
1994 Jul 1;54(13):3544-3552, Cancer research
— id: 16331, year: 1994, vol: 54, page: 3544, stat: Journal Article,

Expression of Wnt-1 in PC12 cells results in modulation of plakoglobin and E-cadherin and increased cellular adhesion
Bradley RS; Cowin P; Brown AM
1993 Dec;123(6 Pt 2):1857-1865, Journal of cell biology
— id: 16332, year: 1993, vol: 123, page: 1857, stat: Journal Article,

Nomenclature of the desmosomal cadherins
Buxton RS; Cowin P; Franke WW; Garrod DR; Green KJ; King IA; Koch PJ; Magee AI; Rees DA; Stanley JR; et al.
1993 May;121(3):481-483, Journal of cell biology
— id: 16333, year: 1993, vol: 121, page: 481, stat: Journal Article,

Components of intercellular adhesive junctions and their role in morphogenesis
Cowin P; Brown A
Molecular basis of morphogenesis New York : Wiley-Liss, 1993,
— id: 3526, year: 1993, vol: , page: 49, stat: Chapter,

Desmocollins form a distinct subset of the cadherin family of cell adhesion molecules
Mechanic S; Raynor K; Hill JE; Cowin P
1991 May 15;88(10):4476-4480, Proceedings of the National Academy of Sciences of the United States of America
— id: 14021, year: 1991, vol: 88, page: 4476, stat: Journal Article,

Desmoglein shows extensive homology to the cadherin family of cell adhesion molecules
Goodwin L; Hill JE; Raynor K; Raszi L; Manabe M; Cowin P
1990 Dec 31;173(3):1224-1230, Biochemical & biophysical research communications
— id: 14242, year: 1990, vol: 173, page: 1224, stat: Journal Article,

Molecular cloning and amino acid sequence of human plakoglobin, the common junctional plaque protein
Franke WW; Goldschmidt MD; Zimbelmann R; Mueller HM; Schiller DL; Cowin P
1989 Jun;86(11):4027-4031, Proceedings of the National Academy of Sciences of the United States of America
— id: 16334, year: 1989, vol: 86, page: 4027, stat: Journal Article,

The desmosomal plaque and the cytoskeleton
Franke WW; Cowin P; Schmelz M; Kapprell HP
1987 ;125(3):26-48, CIBA Foundation symposium
— id: 16337, year: 1987, vol: 125, page: 26, stat: Journal Article,

Immunolocalization of plakoglobin in endothelial junctions: identification as a special type of Zonulae adhaerentes
Franke WW; Kapprell HP; Cowin P
1987 ;59(3):205-218, Biology of the cell
— id: 16338, year: 1987, vol: 59, page: 205, stat: Journal Article,

Plakoglobin is a component of the filamentous subplasmalemmal coat of lens cells
Franke WW; Kapprell HP; Cowin P
1987 Jun;43(3):301-315, European journal of cell biology
— id: 16336, year: 1987, vol: 43, page: 301, stat: Journal Article,

Biochemical characterization of the soluble form of the junctional plaque protein, plakoglobin, from different cell types
Kapprell HP; Cowin P; Franke WW
1987 Aug 3;166(3):505-517, European journal of biochemistry
— id: 16335, year: 1987,