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Pierre D. McCrea, Ph.D.

Present Title & Affiliation

Primary Appointment

Deputy Chair, Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, TX
Professor, Department of Biochemistry and Molecular Biology, 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 1000
Houston, TX 77030
Room Number: BSRB S9.8136A
Phone: 713-834-6277
Fax: 713-792-0346

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

Experience/Service

Other Appointments/Responsibilities

Deputy Chair, University of Texas MD Anderson Cancer Center, Houston, TX, 2010-present

Honors and Awards

2013 MDACC Educator of the Month (March 2013)
2012-present MDACC Awarded Title of "Distinguished Teaching Professor"
2011-2012 GSBS Reappointment with Highest Commendation
2010 Elected to the MDACC Academy of Health Science Education
2007 Elected to the UT Academy of Health Science Education
2006 GSBS Highest Commendation for Graduate Education (awarded <2% Faculty)
2006 MDACC William Randolpf Hearst Faculty Achievement Award in Education
1998-2002 American Heart Association/ National, Established Investigator Award
1998 GSBS Dean’s Excellence Award
1996-2006 Kleberg Foundation Junior Faculty Award
1991-1993 American Heart Association, California Affiliate, Postdoctoral Fellowship
1989-1991 NIH Individual National Research Award, Postdoctoral Fellowship
1988-1989 Cystic Fibrosis Research, Incorporated, Postdoctoral Fellowship
1979-1983 NIH Pre-doctoral Research Training Fellowship

Selected Publications

Peer-Reviewed Original Research Articles

1. DR Chang, D Martinez Alanis, RK Miller, H Akiyama, PD McCrea, J Chen. Lung epithelial branching program antagonizes alveolar differentiation. PNAS-USA 110(45):18042-51, 9/2013. PMCID: PMC3831485.
2. HY Jung, S Jun, MS Lee, HC Kim, X Wang, H Ji, PD McCrea, JI Park. PAF and EZH2 Induce Wnt/β-Catenin Signaling Hyperactivation. Mol Cell 52(2):193-205, 9/2013.
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. Shahi P, Park D, Pond AC, Seethammagari M, Chiou SH, Cho K, Carstens JL, Decker WK, McCrea PD, Ittmann MM, Rosen JM, Spencer DM. Activation of Wnt signaling by chemically induced dimerization of LRP5 disrupts cellular homeostasis. PLoS One 7(1):e30814, 2012. e-Pub 1/27/2012. PMCID: PMC3267738.
5. 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.
6. Tran HT, Delvaeye M, Verschuere V, Descamps E, Crabbe E, Van Hoorebeke L, McCrea P, Adriaens D, Van Roy F, Vleminckx K. ARVCF depletion cooperates with Tbx1 deficiency in the development of 22q11.2DS-like phenotypes in Xenopus. Dev Dyn 240(12):2680-7, 12/2011. e-Pub 10/2011. PMID: 22028109.
7. Cho K, Lee M, Gu D, Munoz WA, Ji H, Kloc M, McCrea PD. Kazrin, and its binding partners ARVCF- and delta-catenin, are required for Xenopus laevis craniofacial development. Dev Dyn 240(12):2601-12, 12/2011. e-Pub 10/25/2011. PMID: 22028074.
8. Miller RK, Canny SG, Jang CW, Cho K, Ji H, Wagner DS, Jones EA, Habas R, McCrea PD. Pronephric tubulogenesis requires Daam1-mediated planar cell polarity signaling. J Am Soc Nephrol 22(9):1654-64, 9/2011. e-Pub 7/2011. PMCID: PMC3171937.
9. 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.
10. 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.
11. Cho K, Vaught TG, Ji H, Gu D, Papasakelariou-Yared C, Horstmann N, Jennings JM, Lee M, Sevilla LM, Kloc M, Reynolds AB, Watt FM, Brennan RG, Kowalczyk AP, McCrea PD. Xenopus Kazrin interacts with ARVCF-catenin, spectrin and p190B RhoGAP, and modulates RhoA activity and epithelial integrity. J Cell Sci 123(Pt 23):4128-44, 12/2010. e-Pub 11/2010. PMCID: PMC2987443.
12. McCrea PD, Gu D. The catenin family at a glance. J Cell Sci 123(Pt 5):637-42, 3/2010. PMCID: PMC2823574.
13. Miller RK, McCrea PD. Wnt to build a tube: contributions of Wnt signaling to epithelial tubulogenesis. Dev Dyn 239(1):77-93, 1/2010. PMID: 19681164.
14. 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.
15. Park JI, Venteicher AS, Hong JY, Choi J, Jun S, Shkreli M, Chang W, Meng Z, Cheung P, Ji H, McLaughlin M, Veenstra TD, Nusse R, McCrea PD, Artandi SE. Telomerase modulates Wnt signalling by association with target gene chromatin. Nature 460(7251):66-72, 7/2009. PMID: 19571879.
16. Lyons JP, Miller RK, Zhou X, Weidinger G, Deroo T, Denayer T, Park JI, Ji H, Hong JY, Li A, Moon RT, Jones EA, Vleminckx K, Vize PD, McCrea PD. Requirement of Wnt/Beta-catenin signaling in pronephric kidney development. Mech Dev 126(3-4):142-159, Mar-Apr, 3/2009. e-Pub 12/2008. PMCID: PMC2684468.
17. Reintsch WE, Mandato CA, McCrea PD, Fagotto F. Inhibition of cell adhesion by xARVCF indicates a regulatory function at the plasma membrane. Dev Dyn 237(9):2328-2341, 9/2008. PMID: 18729204.
18. Zhang C, Cho K, Huang Y, Lyons JP, Zhou X, Sinha K, McCrea PD, de Crombrugghe B. Inhibition of Wnt signaling by the osteoblast-specific transcription factor Osterix. Proc Natl Acad Sci U S A 105(19):6936-6941, 5/13/2008. e-Pub 5/5/2008. PMCID: PMC2383965.
19. Tao Q, Nandadasa S, McCrea PD, Heasman J, Wylie C. G protein-coupled signals control cortical actin assembly by controlling cadherin expression in the early Xenopus embryo. Development 134(14):2651-2661, 7/2007. e-Pub 6/13/2007. PMID: 17567666.
20. McCrea PD, Park JI. Developmental functions of the P120-catenin sub-family. Biochim Biophys Acta 1773(1):17-33, 1/2007. e-Pub 7/1/2006. PMID: 16942809.
21. Kreiman EL, Morales FC, Takahashi Y, Adams H, Liu TJ, McCrea PD, Georgescu MM. Cortical stabilization of Beta-catenin contributes to NHERF-1/EBP50 tumor suppressor function. Oncogene 26:5290-5299, 2007.
22. 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.
23. van Roy FM, McCrea PD. A role for Kaiso-p120ctn complexes in cancer? Nat Rev Cancer 5(12):956-64, 12/2005. PMID: 16294216.
24. 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.
25. 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.
26. Ciesiolka M, Delvaeye M, Van Imschoot G, Verschuere V, McCrea P, van Roy F, Vleminckx K. p120 catenin is required for morphogenetic movements involved in the formation of the eyes and the craniofacial skeleton in Xenopus. J Cell Sci 117(Pt 18):4325-39, 8/15/2004. e-Pub 8/3/2004. PMID: 15292404.
27. Lyons JP, Mueller UW, Ji H, Everett C, Fang X, Hsieh JC, Barth AM, McCrea PD. Wnt-4 activates the canonical beta-catenin-mediated Wnt pathway and binds Frizzled-6 CRD: functional implications of Wnt/beta-catenin activity in kidney epithelial cells. Exp Cell Res 298(2):369-87, 8/15/2004. PMID: 15265686.
28. Akiyama H, Lyons JP, Mori-Akiyama Y, Yang X, Zhang R, Zhang Z, Deng JM, Taketo MM, Nakamura T, Behringer RR, McCrea PD, de Crombrugghe B. Interactions between Sox9 and beta-catenin control chondrocyte differentiation. Genes Dev 18(9):1072-87, 5/2004. PMCID: PMC406296.
29. Fang X, Ji H, Kim SW, Park JI, Vaught TG, Anastasiadis PZ, Ciesiolka M, McCrea PD. Vertebrate development requires ARVCF and p120 catenins and their interplay with RhoA and Rac. J Cell Biol 165(1):87-98, 4/2004. e-Pub 4/2004. PMCID: PMC2172091.
30. Shonukan O, Bagayogo I, McCrea P, Chao M, Hempstead B. Neurotrophin-induced melanoma cell migration is mediated through the actin-bundling protein fascin. Oncogene 22(23):3616-23, 6/5/2003. PMID: 12789270.
31. Tepera SB, McCrea PD, Rosen JM. A beta-catenin survival signal is required for normal lobular development in the mammary gland. J Cell Sci 116(Pt 6):1137-49, 3/15/2003. PMID: 12584256.
32. Kim SW, Fang X, Ji H, Paulson AF, Daniel JM, Ciesiolka M, van Roy F, McCrea PD. Isolation and characterization of XKaiso, a transcriptional repressor that associates with the catenin Xp120(ctn) in Xenopus laevis. J Biol Chem 277(10):8202-8, 3/2002. e-Pub 12/2001. PMID: 11751886.
33. Adam L, Vadlamudi RK, McCrea P, Kumar R. Tiam1 overexpression potentiates heregulin-induced lymphoid enhancer factor-1/beta -catenin nuclear signaling in breast cancer cells by modulating the intercellular stability. J Biol Chem 276(30):28443-50, 7/2001. PMID: 11328805.
34. Grothey A, Hashizume R, Ji H, Tubb BE, Patrick CW, Jr, Yu D, Mooney EE, McCrea PD. C-erbB-2/ HER-2 upregulates fascin, an actin-bundling protein associated with cell motility, in human breast cancer cell lines. Oncogene 19:4864-75, 10/2000. PMID: 11039904.
35. Grothey A, Hashizume R, Sahin AA, McCrea PD. Fascin, an actin-bundling protein associated with cell motility, is upregulated in hormone receptor negative breast cancer. Br J Cancer 83:870-3, 10/2000. PMID: 10970687.
36. Paulson AF, Mooney E, Fang X, Ji H, McCrea PD. Xarvcf, Xenopus member of the p120 catenin subfamily associating with cadherin juxtamembrane region. J Biol Chem 275:30124-31, 9/2000. PMID: 10899158.
37. Montross WT, Ji H, McCrea PD. A beta-catenin/engrailed chimera selectively suppresses Wnt signaling. J Cell Sci 113 ( Pt 10):1759-70, 5/2000. PMID: 10769207.
38. Hu W, McCrea PD, Deavers M, Kavanagh JJ, Kudelka AP, Verschraegen CF. Increased expression of fascin, motility associated protein, in cell cultures derived from ovarian cancer and in borderline and carcinomatous ovarian tumors. Clin Exp Metastasis 18:83-8, 2000. PMID: 11206843.
39. Paulson AF, Fang X, Ji H, Reynolds AB, McCrea PD. Misexpression of the catenin p120(ctn)1A perturbs Xenopus gastrulation but does not elicit Wnt-directed axis specification. Dev Biol 207:350-63, 3/1999. PMID: 10068468.
40. Wong V, Ching D, McCrea PD, Firestone GL. Glucocorticoid down-regulation of fascin protein expression is required for the steroid-induced formation of tight junctions and cell-cell interactions in rat mammary epithelial tumor cells. J Biol Chem 274(9):5443-53, 2/1999. PMID: 10026156.
41. Liu D, el-Hariry I, Karayiannakis AJ, Wilding J, Chinery R, Kmiot W, McCrea PD, Gullick WJ, Pignatelli M. Phosphorylation of beta-catenin and epidermal growth factor receptor by intestinal trefoil factor. Lab Invest 77(6):557-63, 12/1997. PMID: 9426392.
42. Hunt JF, McCrea PD, Zaccai G, Engelman DM. Assessment of the aggregation state of integral membrane proteins in reconstituted phospholipid vesicles using small angle neutron scattering. J Mol Biol 273(5):1004-19, 11/1997. PMID: 9367787.
43. Wilding J, Vousden KH, Soutter WP, McCrea PD, Del Buono R, Pignatelli M. E-cadherin transfection down-regulates the epidermal growth factor receptor and reverses the invasive phenotype of human papilloma virus-transfected keratinocytes. Cancer Res 56(22):5285-92, 11/1996. PMID: 8912870.
44. Tao YS, Edwards RA, Tubb B, Wang S, Bryan J, McCrea PD. beta-Catenin associates with the actin-bundling protein fascin in a noncadherin complex. J Cell Biol 134:1271-81, 9/1996. PMID: 8794867.
45. Aghib DF, McCrea PD. The E-cadherin complex contains the src substrate p120. Exp Cell Res 218:359-69, 5/1995. PMID: 7537697.
46. Funayama N, Fagotto F, McCrea P, Gumbiner BM. Embryonic axis induction by the armadillo repeat domain of beta-catenin: evidence for intracellular signaling. J Cell Biol 128:959-68, 3/1995. PMID: 7876319.
47. Reynolds AB, Daniel J, McCrea PD, Wheelock MJ, Wu J, Zhang Z. Identification of a new catenin: the tyrosine kinase substrate p120cas associates with E-cadherin complexes. Mol Cell Biol 14(12):8333-42, 12/1994. PMID: 7526156.
48. Heasman J, Crawford A, Goldstone K, Garner-Hamrick P, Gumbiner B, McCrea P, Kintner C, Noro CY, Wylie C. Overexpression of cadherins and underexpression of beta-catenin inhibit dorsal mesoderm induction in early Xenopus embryos. Cell 79:791-803, 12/1994. PMID: 7528101.
49. McCrea PD, Brieher WM, Gumbiner BM. Induction of a secondary body axis in Xenopus by antibodies to beta-catenin. J Cell Biol 123:477-84, 10/1993. PMID: 8408227.
50. Gumbiner BM, McCrea PD. Catenins as mediators of the cytoplasmic functions of cadherins. J Cell Sci Suppl 17:155-8, 1993. PMID: 8144692.
51. Peifer M, McCrea PD, Green KJ, Wieschaus E, Gumbiner BM. The vertebrate adhesive junction proteins beta-catenin and plakoglobin and the Drosophila segment polarity gene armadillo form a multigene family with similar properties. J Cell Biol 118:681-91, 8/1992. PMID: 1639851.
52. McCrea PD, Turck CW, Gumbiner B. A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. Science 254:1359-61, 11/1991. PMID: 1962194.
53. McCrea PD, Gumbiner BM. Purification of a 92-kDa cytoplasmic protein tightly associated with the cell-cell adhesion molecule E-cadherin (uvomorulin). Characterization and extractability of the protein complex from the cell cytostructure. J Biol Chem 266:4514-20, 3/1991. PMID: 1999432.
54. Choi YS, Sehgal R, McCrea P, Gumbiner B. A cadherin-like protein in eggs and cleaving embryos of Xenopus laevis is expressed in oocytes in response to progesterone. J Cell Biol 110:1575-82, 5/1990. PMID: 2335564.
55. McCrea PD, Engelman DM, Popot JL. Topography of integral membrane proteins: hydrophobicity analysis vs. immunolocalization. Trends Biochem Sci 13(8):289-90, 8/1988. PMID: 3154280.
56. McCrea PD, Popot JL, Engelman DM. Transmembrane topography of the nicotinic acetylcholine receptor delta subunit. Embo J 6(12):3619-26, 12/1987. PMID: 3428268.
57. McCrea PD. Transmembrane topology of the of the acetylcholine receptor examined in reconstituted vesicles. Ph.D. Dissertation, Yale University, 1987.
58. NO Markham, CA Doll, MR Dohn, RK Miller, H Yu, PD McCrea, JT Gamse, AB Reynolds. DIPA family coiled coils bind conserved isoform-1 specific head domain of p120-catenin family: potential roles in N-cadherin associated disease. Mol Biol Cell. Submitted.
59. 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. Submitted.
Other Articles
1. Grothey A, McCrea PD. Re: Preferential adhesion of prostate cancer cells to a human bone marrow endothelial cell line. J Natl Cancer Inst 90:547, 4/1998. PMID: 9539253.

Book Chapters

1. WA Muñoz, AK Sater, PD McCrea. Development of Neural Tissues in Xenopus laevis, Xenopus Development. In: Xenopus Development. Ed(s) M Kloc, JZ Kubiak. Wiley Press. In Press. ISBN: 9781118492819.
2. RK Miller, M Lee, PD McCrea. The Xenopus pronephros: Leaps towards understanding kidney development. In: Xenopus Development. Ed(s) M Kloc, JZ Kubiak. Wiley Press. In Press. ISBN: 9781118492819.
3. RK Miller, JY Hong, WA Munoz, PD McCrea. Beta-catenin versus the other armadillo catenins: assessing our current view of canonical Wnt signaling. In: The molecular biology of cadherins. 116, Progress in Molecular Biology and Translational Science. Ed(s) Frans van Roy; Series Editor-in-Chief: P. Michael Conn, 387-407, 2013.

Last updated: 9/3/2013