Dolly Mehta

My lab investigates interactive signaling between non-phagocytic (i.e., endothelial cells) and phagocytic cells (i.e., monocytes/macrophages) in regulating tissue function. We seek to understand how stressors (such as ligands for G-protein coupled receptors or toll-like receptors) on these cell types trigger metabolic and epigenetic changes to alter tissue function under physiological setting versus pathological (i.e., cancer) settings.

Specific projects are:

1) Investigate the non-canonical function of the tumor suppresor, PTEN, in generating a reparative and anti-inflammatory population of endothelial cells that maintain normal tissue function.

2) Investigate the role of focal adhesion kinase (FAK) in maintaining cellular tension and epigenetics.

3) Determine mechanisms inducing the synthesis of GPCR, S1PR1, and how it determines physiological versus pathological angiogenesis.

4) Investigate the role of S1P and cAMP metabolism in macrophages in dictating tissue macrophage phenotype and inflammatory function.

Yazbeck P, Tauseef M, Kruse K, Amin MR, Sheikh R, Feske S, Komarova Y, Mehta D. STIM1 Phosphorylation at Y361 Recruits Orai1 to STIM1 Puncta and Induces Ca2+ Entry. Sci Rep. 2017 Feb 20;7:42758.

Rajput C, Tauseef M, Farazuddin M, Yazbeck P, Amin MR, Avin Br V, Sharma T, Mehta D. MicroRNA-150 Suppression of Angiopoetin-2 Generation and Signaling Is Crucial for Resolving Vascular Injury. Arterioscler Thromb Vasc Biol. 2016 Feb;36(2):380-8.

Tauseef M, Farazuddin M, Sukriti S, Rajput C, Meyer JO, Ramasamy SK, Mehta D. Transient receptor potential channel 1 maintains adherens junction plasticity by suppressing sphingosine kinase 1 expression to induce endothelial hyperpermeability. FASEB J. 2016 Jan;30(1):102-10.

Rajput C, Kini V, Smith M, Yazbeck Y, Chavez A, Thennes T, Knezevic N, Mehta D. N-WASP plays a critical role in re-annealing VE-cadherin adherens junctions. J Biol Chem. 288:4241-50, 2013.

Tauseef M, Knezevic N, Chava KR, Smith M, Sukriti S,Gianaris N, Obukhov AG, Vogel SM, Schraufnagel DE, Dietrich A, Birnbaumer L, Malik AB, Mehta D. TLR4 Activation of TRPC6-dependent calcium signaling mediates endotoxin-induced lung vascular permeability and inflammation. J Exp Med. 209:1953-68, 2012.

Chava KR, Tauseef M, Mehta D. Cyclic AMP response element binding (CREB) protein prevents endothelial permeability increase through transcriptional controlling p190RhoGAP expression. Blood. 119:308-19, 2012.

Kini V, Chavez A, Mehta D. A new role for PTEN in regulating transient receptor potential canonical channel 6-mediated Ca2+ entry, endothelial permeability and angiogenesis. J Biol Chem. 285:33082-91, 2010.

Knezevic N, Tauseef M, Thennes T, Mehta D.The G protein beta gamma subunit mediates re-annealing of adherens junctions to reverse endothelial permeability increase by thrombin. J Exp Med. 206:2761-77, 2009.

Tauseef M, Kini V, Knezevic N, Saba J, Vogel S, Ramchandran R, Malik AB, Mehta D. Activation of sphingosine kinase-1 reverses the increase in lung vascular permeability through sphingosine-1-phosphate receptor signaling in endothelial cells. Circ Res.103:1164-72, 2008.

Nebojsa K, Roy A, Timblin B, Konstantoulaki M, Malik AB, Mehta D. Requirement for GDI-1 phosphorylation at serine 96 in the mechanism of RhoA activation and increased endothelial permeability. Mol Cell Biol. 27:6323-33, 2007.

Holinstat M, Knezevic N, Broman M, Samarel A, Malik AB, Mehta D. Suppression of rho activity by focal adhesion kinase-induced activation of p190RhoGAP: Role in restoring endothelial barrier function. J Biol Chem. 281:2296-305, 2006.

Jho DH, Mehta D., Ahmmed 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. 96:1282-90, 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.