Sadashiva S. Karnik Ph.D.

Staff

  • Department of Molecular Cardiology
  • Lerner Research Institute / NB50
  • 9500 Euclid Avenue
  • Cleveland, Ohio 44195
  • karniks@ccf.org
  • (216) 444-1269
  • (216) 444-9263

  1. Regulation of physiology and pathology through AT1R in transgenic mouse models.
  2. Principles governing GPCR functions through structure-function analysis of AT1R. 
  3. The AT1R initiated signal transduction through application of proteomic, global gene and miRNA analysis. 
  4. Genotype-phenotype relationship studies in angiotensin receptor expressing mouse models.
  5. Novel GPCR signaling paradigms through elucidation of ligand-specific signaling in AT1R.

In other words ...

Two transmembrane signaling receptors mediate the in vivo effects of the renin angiotensin system. Of these two, the Angiotensin II (AngII) type 1 receptor (AT1R) plays an indispensable role in physiological regulation of blood pressure and water-electrolyte balance. Pathological states such as hypertension, cardiac hypertrophy and heart failure (HF) are observed when AT1R activation becomes chronic. The AT1R is a target for classical sartan-family of antihypertensive drugs. Currently these drugs are indicated for treatment of additional disease conditions such as myocardial infarction, aortic aneurism,  Marfan syndrome and diabetic nephropathy and retinopathy, which makes the sartans a target for continued drug development. AT1R is a member of G-protein coupled receptor (GPCR) family, which are transmembrane proteins that transform extracellular hormonal or physical cues into specific amplified intracellular signals.

We study all aspects of AT1R structure, function, physiology, genetics and signaling. The approaches we use include transgenesis, molecular pharmacology, ligand design, membrane protein biochemistry, protein-protein interaction, signal transduction, gene regulation, micoRNA regulation, proteomics and post-translational modifications.

  • Virginia Brown
  • Animal Husbandry Technician I
  • Location:NB5-115
  • Phone:(216) 445-6636
  • brownv6@ccf.org
  • Arunachal Chatterjee Ph.D.
  • Postdoctoral Fellow
  • Location:NB5-15
  • Phone:(216) 445-6636
  • chattea@ccf.org
  • Russell William Desnoyer
  • Lead Research Technologist
  • Location:NB5-15
  • Phone:(216) 445-6636
  • Fax:(216) 444-9263
  • desnoyr@ccf.org
  • Kalyan C Tirupula Ph.D.
  • Postdoctoral Fellow
  • Location:NB5-115
  • Phone:(216) 445-6636
  • tirupuk@ccf.org
  • Hamiyet Unal Ph.D.
  • Postdoctoral Fellow
  • Location:NB5-15
  • Phone:(216) 394-7320
  • unalh@ccf.org

HIGHLIGHTED PUBLICATIONS

  1. Unal H, Karnik SS. Domain coupling in GPCRs: the engine for induced conformational changes. Trends Pharmacol. Sci. 33: 79-88, PMCID:PMC3273637
  2. Karnik SS, Unal H. (2012) Angiotensin II Receptor-Induced Cardiac Remodeling in Mice Without Angiotensin II. Hypertension 59: 542-544, PMCID: PMC3310368
  3. Bhatnagar et al. (2012) Interaction of G-protein ß? complex with Chromatin Modulates GPCR-dependent Gene Regulation, PLoS One. doi: 10.1371/ PMCID: PMC3541368 
  4. Ramchandran et al. (2006) Angiotensinergic stimulation of vascular endothelium in mice causes hypotension, bradycardia and attenuated angiotensin response. Proc. Natl. Acad. Sci. U.S.A. 103:19087-19097.

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