Lakshmi Santhanam, PhD

Primary Academic Title

Associate Professor of Anesthesiology and Critical Care Medicine

Background

Additional Academic Titles

Associate Professor of Biomedical Engineering

Research Interests

Cardiovascular disease, vascular stiffening, atherosclerosis

Lab Website

Lakshmi Santhanam Lab

• Investigators in the Lakshmi Santhanam Lab examine the fundamental mechanisms behind cardiovascular disease. They are particularly interested in better understanding how nitric oxide-mediated S-nitrosylation (a post-translational protein modification) impacts protein function and trafficking in the vasculature as well as how this relationship influences matrix remodeling and vascular stiffening.

Selected Publications

• 1. Santhanam L, Tuday EC, Webb AK, Dowzicky P, Kim JH, Oh YJ, Sikka G, Kuo M, Halushka MK, Macgregor AM, Dunn J, Gutbrod S, Yin D, Shoukas A, Nyhan D, Flavahan NA, Belkin AM, Berkowitz DE. Decreased S-nitrosylation of tissue transglutaminase contributes to age-related increases in vascular stiffness. Circ Res. 2010 Jul 9;107(1):117-25. PMID: 20489165
  2. Jandu SK, Webb AK, Pak A, Sevinc B, Nyhan D, Belkin AM, Flavahan NA, Berkowitz DE, Santhanam L. Nitric oxide regulates tissue transglutaminase localization and function in the vasculature. Amino Acids. 2011 Oct 8. [Epub ahead of print] PMCID: PMC3744185
  3. Santhanam L, Berkowitz DE, Belkin AM. Nitric oxide regulates non-classical secretion of tissue transglutaminase. Commun Integr Biol. 2011 Sep;4(5):584-6. PMCID: PMC3204136
  4. Jung SM, Jandu S, Steppan J, Belkin A, An SS, Pak A, Choi EY, Nyhan D, Butlin M, Viegas K, Avolio AP, Berkowitz DE, Santhanam L. Increased Tissue Transglutaminase Activity Contributes to Central Vascular Stiffness in eNOS Knockout Mice. Am J Physiol Heart Circ Physiol. 2013 Jul 19.
  5. Steppan J, SikkaG, Jandu S, Barodka V, Halushka MK, Flavahan N, Belkin AM, Nyhan D, Butlin M, Avolio A, Berkowitz DE, and Santhanam L. Exercise, vascular stiffness, and tissue transglutaminase. J of Am Heart Assoc. (This article was accompanied by an editorial)
  6. Kuo MM, Barodka V, Abraham TP, Steppan J, Shoukas AA, Butlin M, Avolio A, Berkowitz DE, Santhanam L. Measuring ascending aortic stiffness in vivo in mice using ultrasound. J Vis Exp. 2014 Dec 2;(94)
  7. Santhanam L, Lim HK, Lim HK, Miriel V, Brown T, Patel M, Balanson S, Ryoo S, Anderson M, Irani K, Khanday F, Di Costanzo L, Nyhan D, Hare JM, Christianson DW, Rivers R, Shoukas A, Berkowitz DE. Inducible NO synthase dependent S-nitrosylation and activation of arginase1 contribute to age-related endothelial dysfunction. Circ Res. 2007 Sep 28;101(7):692-702. PMID: 17704205 (This manuscript was accompanied by an editorial)
  8. Santhanam L, Gucek M, Brown TR, Mansharamani M, Ryoo S, Lemmon CA, Romer L, Shoukas AA, Berkowitz DE, Cole RN. Selective fluorescent labeling of S-nitrosothiols (S-FLOS): a novel method for studying S-nitrosation. Nitric Oxide. 2008 Nov;19(3):295-302. PMCID: PMC3705760
  9. Santhanam L, Christianson DW, Nyhan D, Berkowitz DE. Arginase and vascular aging. J Appl Physiol. 2008 Nov;105(5):1632-42.; PMCID: PMC2584835
  10. Dunn J, Gutbrod S, Webb A, Pak A, Jandu SK, Bhunia A, Berkowitz DE, Santhanam L. S-nitrosation of arginase 1 requires direct interaction with inducible nitric oxide synthase. Mol Cell Biochem. 2011 Sep;355(1-2):83-9. PMCID: PMC3744166 Kutz JL, Greaney JL, Santhanam L, Alexander LM. Evidence for a functional vasodilatatory role for hydrogen sulphide in the human cutaneous microvasculature. J Physiol. 2015 May 1;593(9):2121-9.
  11. Smith CJ, Santhanam L, Alexander LM. Rho-Kinase activity and cutaneous vasoconstriction is upregulated in essential hypertensive humans. Microvasc Res. 2013 May;87:58-64
  12. Bruning RS, Santhanam L, Stanhewicz AE, Smith CJ, Berkowitz DE, Kenney WL, Holowatz LA. Endothelial nitric oxide synthase mediates cutaneous vasodilation during local heating and is attenuated in middle-aged human skin. J Appl Physiol 2012 Jun;112(12):2019-26
  13. Smith CJ, Santhanam L, Bruning RS, Stanhewicz A, Berkowitz DE, Holowatz LA. Upregulation of inducible nitric oxide synthase contributes to attenuated cutaneous vasodilation in essential hypertensive humans. Hypertension. 2011 Nov;58(5):935-42. PMCID: PMC3209704
  14. Holowatz LA, Santhanam L, Webb A, Berkowitz DE, Kenney WL. Oral atorvastatin therapy restores cutaneous microvascular function by decreasing arginase activity in hypercholesterolaemic humans. J Physiol. 2011 Apr 15;589(Pt 8):2093-103. PMCID: PMC3090606