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Pierre D. McCrea, Ph.D.

Present Title & Affiliation

Primary Appointment

Professor, Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX

Research Interests

Catenin biology; stem cells; neural development; early vertebrate development; intracellular and nuclear signaling

Background:  Using cell and vertebrate model systems, our lab studies the catenin family of proteins. Catenins transduce developmental (Wnt and additional pathway) signals from the cytoplasm to the nucleus. Being multi-functional, catenins also bind cadherin cell-cell adhesion proteins at the plasma membrane (e.g. at cell-cell junctions), as well as modulate Rho-family (small) GTPases participating in cytoplasmic cytoskeletal control. 

Goals:  We wish to understand the roles of catenins at both developmental and mechanistic levels. In particular our group addresses: 1) lesser-understood catenins such as p120-catenin, ARVCF-catenin, delta-catenin and plakophilin-3 (PKP3); and 2) their involvement in Wnt or other signaling pathways relevant to stemness, differentiation or homeostasis/ regeneration.

While functionally distinct entities, the p120-, ARVCF-, delta- and PKP3-catenins share partial sequence homology with beta-catenin, and each is present in multiple cellular compartments. For example, each binds to cadherin cell-cell adhesion proteins as well as nuclear factors. In the nucleus, beta-catenin activates genes after binding to the TCF/ LEF transcription factors, whereas p120-catenin or delta-catenin (etc.) bind to other transcription factors to regulate gene activity. We recently revealed that complexes of p120-catenin/Kaiso as well as of beta-catenin/TCF directly regulate transcriptional activity at shared developmentally critical genes. Further upstream, we then discovered that p120-catenin interacts with canonical-Wnt pathway modulators only previously known to associate with beta-catenin (e.g. "destruction-complex" components such as Axin, as well as more upstream entities such as Dishevelled and Frodo). Currently, we are evaluating an exciting unexpected interaction of p120-catenin with a powerful transcriptional complex well known to participate in stemness/ differentiation decisions. To widen our understanding of catenin biology, we have further examined additional catenins. For example, we showed that ARVCF is essential in Xenopus development and characterized its direct interaction with the novel protein Kazrin, which is little understood but in common with catenins localizes to both plasma-membrane and nuclear compartments, modulating small-GTPases and potentially gene regulatory functions. We have also probed delta-catenin's roles, and revealed surprisingly, that it is positively regulated by caspase3 cleavage (caspase3 is known to operate also in non-apoptotic settings), generating a large fragment which enters the nucleus to bind, and we expect modulate, a novel Krab-domain zinc-finger repressor we named ZIFCAT. Most recently, we resolved PKP3-catenin's interaction with ETV1, a DNA-binding transcriptional activator important in neural development (dopaneurgic-pathway, etc.), whose activity is positively enhanced by PKP3. In the coming years, we aim to confront the larger question as to the extent that catenin nuclear functions are networked or distinct in reaching developmental objectives.

Office Address

The University of Texas MD Anderson Cancer Center
6767 Bertner Street
Unit Number: Unit 1010
Houston, TX 77030
Room Number: BSRB S9.8136A
Phone: 713-834-6277
Fax: 713-792-0346
Email: pdmccrea@mdanderson.org

Education & Training

Degree-Granting Education

1986 Yale University, New Haven, CT, PHD, Molecular Biophysics and Biochemistry
1981 Yale University, New Haven, CT, M.PHIL., Molecular Biophysics and Biochemistry
1979 Bowdoin College, Brunswick, ME, AB, Biochemistry

Postgraduate Training

1993 Postdoctoral Associate, Cellular Biochemistry and Biophysics Program, Sloan-Kettering Cancer Institute, New York, NY, Dr. Barry Gumbiner
1988-1992 Postdoctoral Fellow, Cell and Developmental Biology, University of California-San Francisco, San Francisco, CA, Dr. Barry Gumbiner
1986-1987 Postdoctoral Associate, Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, Dr. Donald Engelman

Selected Publications

Peer-Reviewed Original Research Articles

1. Lee M, Ji H, Furuta Y, Park JI, McCrea PD.. P120-catenin regulates REST/CoREST, and modulates mouse embryonic stem cell differentiation. J Cell Sci, 2014 Jul 29, 7/2014. PMID: 25074806.
2. Munoz WA, Lee M, Miller RK, Ahmed Z, Ji H, Link TM, Lee GR, Kloc M, Ladbury JE, McCrea PD.. Plakophilin-3 catenin associates with the ETV1/ER81 transcription factor to positively modulate gene activity. PLoS One 9(1):e86784, 1/2014. PMCID: PMCPMC3903613.
3. Hong JY, Park JI, Lee M, Muñoz WA, Miller RK, Ji H, Gu D, Sokol SY, McCrea PD. Down's-syndrome-related kinase Dyrk1A modulates the p120-catenin-Kaiso trajectory of the Wnt signaling pathway. J Cell Sci 125(Pt 3):561-9, 2/2012. PMCID: PMC3367828.
4. Munoz WA, Kloc M, Cho K, Lee M, Hofmann I, Sater A, Vleminckx K, McCrea PD. Plakophilin-3 is required for late embryonic amphibian development, exhibiting roles in ectodermal and neural tissues. PLoS One 7(4):e34342, 2012. e-Pub 4/2012. PMCID: PMC3320641.
5. Gu D, Tonthat NK, Lee M, Ji H, Bhat KP, Hollingsworth F, Aldape KD, Schumacher MA, Zwaka TP, McCrea PD. Caspase-3 cleavage links delta-catenin to the novel nuclear protein ZIFCAT. J Biol Chem 286(26):23178-88, 7/1/2011. e-Pub 5/11/2011. PMCID: PMC3123085.
6. Hong JY, Park JI, Cho K, Gu D, Ji H, Artandi SE, McCrea PD. Shared molecular mechanisms regulate multiple catenin proteins: canonical Wnt signals and components modulate p120-catenin isoform-1 and additional p120 subfamily members. J Cell Sci 123(Pt 24):4351-65, 12/2010. e-Pub 11/2010. PMCID: PMC2995616.
7. Gu D, Sater AK, Ji H, Cho K, Clark M, Stratton SA, Barton MC, Lu Q, McCrea PD. Xenopus delta-catenin is essential in early embryogenesis and is functionally linked to cadherins and small GTPases. J Cell Sci 122(Pt 22):4049-61, 11/2009. e-Pub 10/2009. PMCID: PMC2776500.
8. Park JI, Ji H, Jun S, Gu D, Hikasa H, Li L, Sokol SY, McCrea PD. Frodo links Dishevelled to the p120-catenin/Kaiso pathway: distinct catenin subfamilies promote Wnt signals. Dev Cell 11(5):683-95, 11/2006. PMID: 17084360.
9. Park JI, Kim SW, Lyons JP, Ji H, Nguyen TT, Cho K, Barton MC, Deroo T, Vleminckx K, Moon RT, McCrea PD. Kaiso/p120-catenin and TCF/beta-catenin complexes coordinately regulate canonical Wnt gene targets. Dev Cell 8(6):843-54, 6/2005. PMID: 15935774.
10. Kim SW, Park JI, Spring CM, Sater AK, Ji H, Otchere AA, Daniel JM, McCrea PD. Non-canonical Wnt signals are modulated by the Kaiso transcriptional repressor and p120-catenin. Nat Cell Biol 6(12):1212-20, 12/2004. e-Pub 11/2004. PMID: 15543138.

Last updated: 9/15/2014