Mehta Lab Interests
Vascular endothelium, a monolayer of endothelial cells and extracellular matrix covering all blood vessels, is the essential barrier for the exchange of solutes and fluid
that maintain tissue fluid balance. It has become progressively clear that complex sets of proteins such as cadherin-catenin complex and focal adhesion complex, which constitute intercellular
junctions and focal adhesions, are the fundamental structure important for maintaining endothelial barrier function. Edemagenic agents such as thrombin by binding to Protease Activating
Receptors (PAR-1) induces a repertoire of signaling events that results in the formation of minute gaps between cells. These gaps allow the passage of albumin and other plasma proteins across
the endothelial monolayer leading to increased lung vascular permeability, a hallmark of acute lung injury. Understanding of specific signaling mechanisms, which regulate the opening and
closing of the junctional barrier are therefore critical in defining the mechanism controlling lung vascular permeability.
Specific Projects in the lab include:
- Determining the role of GDI-1 and RhoGEF downstream of PAR-1 activation in triggering the activation of RhoGTPases, and thereby in signaling the increase in junctional permeability.
- Determine signaling mechanisms, which will help restore endothelial junctional barrier.
Studies use biochemical, genetic, confocal microscopy, and real-time protein dynamics in cultured endothelial cells. In addition, we use mouse lung model to address the role of relevant protein in regulating lung vascular permeability.
- Mehta D, Rahman A, Malik AB. Protein kinase C alpha signals rho guanine nucleotide dissociation inhibitor phosphorylation, rho activation and regulates the endothelial cell barrier function. J. Biol. Chem. 2001;276:22614-22620.
- Mehta D. Emerging role of serine/threonine phosphatase-2B in regulating protein-kinase C-activity and endothelial barrier function. Editorial, Am. J. Physiol. Lung Cell. Mol. Physiol. 2001;281:L544-545.
- Mehta D, Tirupathi C, Sandoval R, Minshall RD, Holinstat M, Malik AB. Modulatory role of focal adhesion kinase in regulating human pulmonary arterial endothelial barrier function. J. Physiol. 2002;539:779-789.
- Holinstat M, Mehta D, Kozasa T, Minshall RD, Malik AB. Protein kinase Calpha-induced p115RhoGEF phosphorylation signals endothelial cytoskeletal rearrangement. J. Biol. Chem. 2003:278(31):28793-8 .
- Mehta D, Ahmmed GU, Paria BC, Holinstat M, Voyno-Yasenetskaya T, Tiruppathi C, Minshall RD, Malik AB. RhoA interaction with inositol 1,4,5-trisphosphate receptor and transient receptor potential channel-1 regulates Ca2+ entry. Role in signaling increased endothelial permeability. J. Biol. Chem. 2003:278(35):33492-500.
- Ahmmed GU, Mehta D, Vogel S, Holinstat M, Paria BC, Tiruppathi C, Malik AB. Protein kinase Ca phosphorylates the TRPC1 channel and regulates store-operated Ca2+ -entry. J. Biol. Chem. 279(20):20941-49, 2004.
- Mehta D. p120: The Guardian of Endothelial Junctional Integrity. Editorial, Am. J. Physiol. Lung Cell. Mol. Physiol 2004;286(6), L1140-42, 2004.
- Mehta D, Bhattacharya J, Matthay MA, Malik AB. Intergrated control of lung fluid balance. Am. J. Physiol. Lung Cell. Mol. Physiol. 287:L1081-90, 2004.
- Mehta D, Minshall RD, Malik, AB. Regulation of Endothelial Barrier Function: Contributions of the Transcellular and Paracellular Pathways. In: Cell Signaling in Vascular Inflammation, edited by Bhattacharya J: Humana, 2005.
- Mehta D, Konstantoulaki M, Ahmmed GU, Malik AB. Sphingosine 1-phosphate-induced mobilization of intracellular Ca2+ mediates Rac activation and adherens junction assembly in endothelial cells. J Biol Chem. 280:17320-8, 2005, 2005.
- Mehta D. Lysophosphatidylcholine: an enigmatic phospholipid. Am. J. Physiol. Lung Cell. Mol. Physiol. 289(2):L174-5, 2005.
- Jho DH, Mehta D, Ahmed G, Gao X-P, Tiruppathi C, Broman MT, Malik AB. Angiopoietin-1 apposes VEGF-induced increase in endothelial permeability by inhibiting calcium entry through TRPC channels. Circ. Res 96(12):1282-90, 2005.
- Mehta D and Malik A.B. Signaling mechanisms regulating endothelial permeability. Physiological Reviews in press.
Postdoctoral Fellow position is available in the Department of Pharmacology to investigate mechanisms regulating lung vascular inflammation and repair. Candidates must have PhD or MD/PhD degree with good publication record and should be able to work independently. Applicant should have experience in mouse handling and determining in vivo function. Training in microRNA and their impact on cell function is a plus. Please provide CV and names and contact information of three references. University of Illinois is an equal opportunity and affirmative action employer. Submit electronic materials preferably as pdf to:firstname.lastname@example.org.