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Joseph H. McCarty, Ph.D.

Present Title & Affiliation

Primary Appointment

Associate Professor, Department of Neurosurgery - Research, The University of Texas MD Anderson Cancer Center, Houston, TX

Research Interests

The McCarty Lab uses mouse genetics to study how integrins and their extracellular matrix (ECM) protein ligands regulate the development and physiology of the central nervous system (CNS). Additional interests include understanding how abnormal regulation of integrin and ECM protein expression and functions lead to CNS pathologies, including birth defects, stroke and cancer. In particular, we study cell adhesion and signaling pathways that mediate bi-directional communication between glial cells and vascular cells within the CNS. The billions of neurons and glial cells in the CNS are intertwined with a complex web of blood vessels. These various neural and vascular cell types dynamically interact with each other to form integrated complexes, or neurovascular units, that regulate the structural and functional integrity of the CNS and have causative links to many CNS pathologies. We have identified integrins and their ECM protein ligands as essential regulators of neurovascular development and physiology in the CNS. One integrin, alphaVbeta8, which is expressed in perivascular neuroepithelial cells and astrocytes, is of particular interest. This integrin is a receptor for latent TGFbeta's (LAP-TGFb's) which are expressed by cells as inactive ECM-associated complexes. Genetic ablation of alphaVbeta8 integrin or the TGFb's lead to strikingly similar developmental neurovascular defects, including abnormal CNS angiogenesis, hemorrhage and premature death. Hence, alphaVbeta8 integrin and latent TGFb's are components of an adhesion and signaling axis that link perivascualr glial cells, vascular basement membranes and cerebral endothelial cells. Current efforts in the lab involve characterizing mechanisms that link the components of this axis as well as using this axis as a foundation to identify other genes and signaling pathways important for neurovascular development and disease.

McCarty Lab Website - Please click this link to view it: http://www.mdanderson.org/education-and-research/departments-programs-and-labs/labs/mccarty-lab/index.html

 

 

Office Address

The University of Texas MD Anderson Cancer Center
Department of Neurosurgery
1515 Holcombe Boulevard
Unit Number: 1004
Houston, TX 77030
Room Number: BSRB S5.8136c
Phone: (713) 792-0429
Email: jhmccarty@mdanderson.org

Education & Training

Degree-Granting Education

1997 University of California, Santa Barbara, CA, PHD, Biochemistry and Molecular Biology
1989 University of Maryland, Baltimore, MD, BS, Biochemistry

Postgraduate Training

1998-2005 Research Fellowship, Molecular Genetics, Massachusetts Institute of Technology, Cambridge, MA, Richard O. Hynes

Honors and Awards

2008-2010 Career Development Award, MDACC Brain Cancer SPORE
2006-2010 New Scholar Award in Aging, Ellison Medical Foundation
1998-2003 Howard Hughes Medical Institute Post-doctoral Research Associate, MIT
1994-1997 American Heart Association Pre-doctoral Fellowship, University of California, Santa Barbara

Professional Memberships

American Association for the Advancement of Science
Member, 2005-present
American Association of Cancer Researchers
Member, 2005-present
American Society for Cell Biology
Member, 2005-present
North American Vascular Biology Organization
Member, 2006-present
Society for Neuroscience
Member, 2008-present

Selected Publications

Peer-Reviewed Original Research Articles

1. Reyes SB, Narayanan A, Tchaicha JH, Shin HS, Lang FF, Aldape KD, Tolias K. McCarty, JH. alphaVbeta8 integrin interacts with RhoGDI1 to regulate and Rac1/Cdc42 activation and drive glioblastoma cell invasion. Molecular Biology of the Cell 4:474-482, 1/2013.
2. Allinson KR, Lee HS, Fruttiger M, McCarty J, Arthur HM. Endothelial expression of TGFβ type II receptor is required to maintain vascular integrity during postnatal development of the central nervous system. PLoS One 7(6):e39336, 6/2012.
3. Mobley AK and McCarty JH. Cre-Lox genetic strategies to selectively delete cell adhesion genes in astrocytes. Methods in Molecular Biology 814:555-70, 1/2012.
4. Hirota, S, Liu, Q, Lee, HS, Hossain, MH, Lacy-Hulbert, A and McCarty, JH. The astrocyte expressed integrin aphaVbeta8 governs endothelial cell growth and sprouting in the developing retina. Development 138(23):5157-66, 12/2011.
5. Tchaicha, JH, Reyes, SB, Shin, J, Hossain, MH, Lang, FF and McCarty, JH. Glioblastoma angiogenesis and tumor cell invasiveness are differentially regulated by beta8 integrin. Cancer Research 71(20):6371-81, 10/2011.
6. Nguyen HL, Park SO, Shin JK, McCarty JH, and Oh SP. TGFβ signaling in endothelial cells, but not neuroepithelial cells, is essential for cerebral vascular development. Laboratory Investigation 91(11):1554-63, 7/2011.
7. Mobley AK and McCarty JH. β8 integrin is essential for neuroblast migration in the rostral migratory stream. Glia. e-Pub 6/2011.
8. Jung Y, Kissil JL, and McCarty JH. β8 Integrin and Band 4.1B Cooperatively Regulate Morphogenesis of the Embryonic Heart. Developmental Dynamics 240(1):2717-7, 1/2011.
9. Tchaicha JH, Mobley AM, Hossain MG, ALdape K, and McCarty JH. A mosaic mouse model of astrocytoma identifies αvβ8 integrin as a negative regulator of yumor angiogenesis. Oncogene 29(31):4460-72, 6/2010. PMCID: PMC3037767.
10. Mobley AK, Tchaicha JH, Shin JK, Hossain MG, McCarty JH. beta8 integrin regulates neurogenesis and neurovascular homeostasis in the adult brain. Journal of Cell Science 122(11):1842-1851, http://jcs.biologists.org/cgi/content/full/122/11/1842, 5/2009.
11. McCarty JH. Cell adhesion and signaling networks in brain neurovascular units. Current Opinion in Hematology 16(3):209-214, 5/2009.

Grant & Contract Support

Title: Targeting Tumor Cell Invasion in Glioblastoma
Funding Source: Cancer Prevention & Research Institute of Texas (CPRIT)
Role: Principal Investigator
Duration: 9/1/2014 - 8/30/2017
 
Title: Signal Transduction by alphaVbeta8 Integrin
Funding Source: NIH/NINDS
Role: Principal Investigator
Duration: 8/15/2014 - 6/1/2019
 
Title: Genetic Models to Study Glial Regulation of Angiogenesis
Funding Source: NIH/NINDS
Role: Co-Principal Investigator
Duration: 7/1/2014 - 6/30/2016
 
Title: Deciphering Mechanisms of Tumor Cell Invasion in Glioblastoma
Funding Source: NIH/NINDS
Role: Principal Investigator
Duration: 9/15/2012 - 5/31/2017

Last updated: 7/31/2014