Srinivas Sithu, Ph.D.

Srinivas Sithu, Ph.D.

srinivas.sithu@louisville.edu
Assistant Professor
University of Lucknow, India, 1999

 

Research:

My broad research goal is to understand the molecular mechanisms of inflammatory disease process in order to inhibit progression of the disease.  In the past several years, I have expanded my research area from studying the role of adhesion molecules in vascular biology to studying lipids and environmental pollutants in endothelial dysfunction, cardiovascular injury, thrombosis and atherogenesis. We observed that endogenous aldehydes, present as ubiquitous environmental chemicals (e.g. acrolein) or exposure to environmental chemicals (e.g. arsenic) which generate free radicals, affect endothelial cells and platelet functions and exacerbate atherosclerosis.

Publications:

  1. Ma, X., Conklin, D.J., Li, F., Dai, Z., Hua, X., Li, Y., Xu-Monette, Z.Y., Young, K.H., Xiong, W., Wysoczynski, M., Sithu, S.D., Srivastava, S., Bhatnagar, A., Li, Y. 2015. The oncogenic microRNA miR-21 promotes regulated necrosis in mice. Nat Commun. 6:7151. PMID: 25990308; PMCID: PMC4440243.
  2. Bartoli, C.R., Dassanayaka, S., Brittian, K.R., Luckett, A., Sithu, S., Siess, T., Raess, D.H., Spence, P.A., Koenig, S.C., Dowling, R.D., D'Souza, S.E. 2014. Insights into the mechanism(s) of von Willebrand factor degradation during mechanical circulatory support. J Thorac Cardiovasc Surg. 147(5):1634-43. PMID: 24139617.
  3. Barski, O.A., Xie, Z., Baba, S.P., Sithu, S.D., Agarwal, A., Cai, J., Bhatnagar, A., Srivastava, S. 2013. Dietary carnosine prevents early atherosclerotic lesion formation in apolipoprotein E-null mice. Arterioscler Thromb Vasc Biol. 33(6):1162-70. PMID: 23559625; PMCID: PMC3869200.
  4. Vladykovskaya, E., Sithu, S.D.* (*co first author), Haberzettl, P., Wickramasinghe, N.S., Merchant, M.L., Hill, B.G., McCracken, J., Agarwal, A., Dougherty, S., Gordon, S.A., Schuschke, D.A., Barski, O.A., O'Toole, T., D'Souza, S.E., Bhatnagar, A., Srivastava, S. 2012. Lipid peroxidation product 4-hydroxy-trans-2-nonenal causes endothelial activation by inducing endoplasmic reticulum stress. J Biol Chem. 287(14):11398-409. PMID: 22228760; PMCID: PMC3322871.
  5. Srivastava, S., Sithu, S.D., Vladykovskaya, E., Haberzettl, P., Hoetker, D.J., Siddiqui, M.A,, Conklin, D.J., D'Souza, S.E., Bhatnagar, A. 2011. Oral exposure to acrolein exacerbates atherosclerosis in apoE-null mice. Atherosclerosis. 215(2):301-8. PMID: 21371710; PMCID: PMC3070047.
  6. Sithu, S.D., Srivastava, S., Siddiqui, M.A., Vladykovskaya, E., Riggs, D.W., Conklin, D.J., Haberzettl, P., O'Toole, T.E., Bhatnagar, A., D'Souza, S.E. 2010. Exposure to acrolein by inhalation causes platelet activation. Toxicol Appl Pharmacol. 248(2):100-10. PMID: 20678513; PMCID: PMC2946419.
  7. Han, S., Arnold, S.A., Sithu, S.D., Mahoney, E.T., Geralds, J.T., Tran, P., Benton, R.L., Maddie, M.A., D'Souza, S.E., Whittemore, S.R., Hagg, T. 2010. Rescuing vasculature with intravenous angiopoietin-1 and alpha v beta 3 integrin peptide is protective after spinal cord injury. Brain. 133(Pt 4):1026-42. PMID: 20375135; PMCID: PMC2850582.
  8. Srivastava, S., Vladykovskaya, E.N., Haberzettl, P., Sithu, S.D., D'Souza, S.E., States, J.C. 2009. Arsenic exacerbates atherosclerotic lesion formation and inflammation in ApoE-/- mice. Toxicol Appl Pharmacol. 241(1):90-100. PMID: 19682479; PMCID: PMC4414341.
  9. Nakashima, S., Arnold, S.A., Mahoney, E.T., Sithu, S.D., Zhang, Y.P., D'Souza, S.E., Shields, C.B., Hagg, T. 2008. Small-molecule protein tyrosine phosphatase inhibition as a neuroprotective treatment after spinal cord injury in adult rats. J Neurosci. 28(29):7293-303. PMID: 18632933; PMCID: PMC2678912.
  10. Essick, E., Sithu, S., Dean, W., D'Souza, S. 2008. Pervanadate-induced shedding of the intercellular adhesion molecule (ICAM)-1 ectodomain is mediated by membrane type-1 matrix metalloproteinase (MT1-MMP). Mol Cell Biochem. 314(1-2):151-9. PMID: 18454303.
  1. Moshal, K.S., Zeldin, D.C., Sithu, S.D., Sen, U., Tyagi, N., Kumar, M., Hughes, W.M. Jr, Metreveli, N., Rosenberger, D.S., Singh, M., Vacek, T.P., Rodriguez, W.E., Ayotunde, A., Tyagi, S.C. 2008. Cytochrome P450 (CYP) 2J2 gene transfection attenuates MMP-9 via inhibition of NF-kappabeta in hyperhomocysteinemia. J Cell Physiol. 215(3):771-81. PMID: 18181170; PMCID: PMC2364732.
  2. Sithu, S.D., English, W.R., Olson, P., Krubasik, D., Baker, A.H., Murphy, G., D'Souza, S.E. 2007. Membrane-type 1-matrix metalloproteinase regulates intracellular adhesion molecule-1 (ICAM-1)-mediated monocyte transmigration. J Biol Chem. 282(34):25010-9. PMID: 17591781
  3. Tsakadze, N.L., Sithu, S.D. (*co first author), Sen, U., English, W.R., Murphy, G., D'Souza, S.E. 2006. Tumor necrosis factor-alpha-converting enzyme (TACE/ADAM-17) mediates the ectodomain cleavage of intercellular adhesion molecule-1 (ICAM-1). J Biol Chem. 281(6):3157-64. PMID: 16332693.
  4. Tsakadze, N.L., Sen, U., Zhao, Z., Sithu, S.D., English, W.R., D'Souza, S.E. 2004. Signals mediating cleavage of intercellular adhesion molecule-1. Am J Physiol Cell Physiol. 287(1):C55-63. PMID: 14973144.