Professor, Department of Neurosurgery - Research, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
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
|1997||University of California, Santa Barbara, CA, USA, PHD, Biochemistry and Molecular Biology|
|1989||University of Maryland, Baltimore, MD, USA, BS, Biochemistry|
|1998-2005||Research Fellowship, Molecular Genetics, Massachusetts Institute of Technology, Cambridge, MA|
|2008||Career Development Award, MDACC Brain Cancer SPORE|
|2006||New Scholar Award in Aging, Ellison Medical Foundation|
|1998||Howard Hughes Medical Institute Post-doctoral Research Associate, MIT|
|1994||American Heart Association Pre-doctoral Fellowship, University of California, Santa Barbara|
- 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, 2013.
- Mobley AK and McCarty JH. Cre-Lox genetic strategies to selectively delete cell adhesion genes in astrocytes. Methods in Molecular Biology 814:555-70, 2012.
- Allinson KR, Lee HS, Fruttiger M, McCarty JH, 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, 2012. e-Pub 2012. PMID: 22745736.
- 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, 2011.
- Mobley AK, McCarty JH. β8 integrin is essential for neuroblast migration in the rostral migratory stream. Glia 59(11):1579-87, 2011. e-Pub 2011. PMID: 21674628.
- Nguyen HL, Lee YJ, Shin J, Lee E, Park SO, McCarty JH, Oh SP. TGFβ signaling in endothelial cells, but not neuroepithelial cells, is essential for cerebral vascular development. Lab Invest 91(11):1554-63, 2011. e-Pub 2011. PMID: 21876535.
- 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, 2011.
- Jung Y, Kissil JL, McCarty JH. β8 Integrin and Band 4.1B Cooperatively Regulate Morphogenesis of the Embryonic Heart. Dev Dyn 240(1):2717-7, 2011. e-Pub 2010. PMID: 21181944.
- 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, 2010. e-Pub 2010.
- Mobley AK, Tchaicha JH, Shin J, Hossain MG, McCarty JH. beta8 integrin regulates neurogenesis and neurovascular homeostasis in the adult brain. J Cell Sci 122(11):1842-1851, 2009. PMID: 19461074.
- McCarty JH. Cell adhesion and signaling networks in brain neurovascular units. Curr Opin Hematol 16(3):209-214, 2009. PMID: 19318941.
|Title:||Deciphering Mechanisms of Tumor Cell Invasion in Glioblastoma|
|Title:||Genetic Models to Study Glial Regulation of Angiogenesis|
|Title:||Signal Transduction by alphaVbeta8 Integrin|
|Title:||Targeting Tumor Cell Invasion in Glioblastoma|
|Funding Source:||Cancer Prevention & Research Institute of Texas (CPRIT)|