Sadashiva "Sadu" Karnik is an Indian-born American molecular biologist who is a Professor in the Molecular Medicine Department of Cleveland Clinic Lerner College of Medicine at Case Western Reserve University. He is also head of the Karnik-lab at the Lerner Research Institute of Cleveland Clinic.[1]

Early life and education

Sadu Karnik earned a B.Sc. degree in botany, zoology and chemistry from Sri Poornaprajna College, Udupi in 1973 and a M.Sc. degree in Clinical Biochemistry by research from Kasturba Medical College, Manipal. He entered the Indian Institute of Science, Department of Microbiology and Cell Biology Bengaluru in 1976 for doctoral studies on Mycobacteriophage in the laboratory of Prof. K.P Gopinathan.[2] His post-doctoral studies were on Bacteriophage Qβ at the laboratory of molecular biologist Martin Billetter of the ETH Institute for Molecular Biology, University of Zurich, Switzerland.[3] He later joined the laboratory of Har Gobind Khorana at Massachusetts Institute of Technology to study disulfide-bonding in integral membrane proteins. He became a naturalized citizen of the United States in 1995.[4]

Career

Karnik started his independent laboratory at the Cleveland Clinic research foundation as assistant staff studying Angiotensin receptor molecular biology and was promoted to full-staff in 2002. In 2000 he received conjoint appointment as professor of chemistry and biology at Cleveland State University (CSU), Cleveland, OH, and in 2003, he became Professor (non-tenure track) of Molecular Medicine in the newly accredited Cleveland Clinic Lerner College of Medicine (CCLCM) at Case Western Reserve University, Cleveland, Ohio.[1] His research programs have been supported by National Institutes of Health funding continuously for the past 25 years.[5]

Research

The Karnik-lab is known for first reporting of constitutive activation, atypical G protein coupling,[6] biased ligand signaling,[7] X-ray structure of antihypertensive drug bound angiotensin[8][9] receptor,[10] and structure-based allosteric ligand of Angiotensin receptors.[11] These discoveries facilitated the development of novel transgenic models of cardiovascular diseases, β-arrestin biased agonists,[12] next generation antihypertensive drugs and novel structures of GPCRs.[10] His current research is aimed at developing novel allosteric ligand drugs for intervention in Preeclampsia due to autoimmunity and Hyperaldosteronism due to adrenal hyperplasia. In 1986 Sadu Karnik and colleagues at MIT reported that production of a functional, light sensing-state of rhodopsin depended on formation of a unique disulfide bond that is conserved in >90% GPCRs.[13][14] The Karnik-lab at Cleveland Clinic extended this finding to other hormone and neurotransmitter GPCRs including β-adrenegic and Angiotensin Receptors.

Awards and honors

Karnik won several fellowships including the Junior Research Fellowship of the Indian Institute of Science, Department of Science Technology (India) Senior Research Fellowship and the Swiss National Science Foundation Fellowship.[15]

  • In 1999, he was awarded Established Investigator of American Heart Association
  • In 2001 he earned the Astra-Zeneca Basic Research Award
  • In 2013 he became Chair of IUPHAR Committee on Angiotensin Receptors and continues his service in that position.

Selected bibliography

References

  1. 1 2 "Lerner Research Institute". www.lerner.ccf.org. Retrieved 2020-12-07.
  2. ↑ Karnik, S. S.; Gopinathan, K. P. (1980-03-01). "Possible involvement of a calcium-stimulated ATP-hydrolyzing activity associated with mycobacteriophage I3 in the DNA injection process". Journal of Virology. 33 (3): 969–975. doi:10.1128/JVI.33.3.969-975.1980. ISSN 0022-538X. PMC 288630. PMID 6445012.
  3. ↑ Karnik, S.; Billeter, M. (1983). "The lysis function of RNA bacteriophage Qbeta is mediated by the maturation (A2) protein". The EMBO Journal. 2 (9): 1521–1526. doi:10.1002/j.1460-2075.1983.tb01617.x. PMC 555316. PMID 11892805.
  4. ↑ Karnik, Sadashiva; Subramaniam, Sriram (2012-12-01). "There is no overkill in biochemistry". Resonance. 17 (12): 1157–1164. doi:10.1007/s12045-012-0132-6. ISSN 0973-712X. S2CID 80667485.
  5. ↑ "NIH Awards by Location and Organization - NIH Research Portfolio Online Reporting Tools (RePORT)". www.report.nih.gov. Retrieved 2020-12-08.
  6. ↑ Tirupula, Kalyan C.; Desnoyer, Russell; Speth, Robert C.; Karnik, Sadashiva S. (2014). "Atypical signaling and functional desensitization response of MAS receptor to peptide ligands". PLOS ONE. 9 (7): e103520. Bibcode:2014PLoSO...9j3520T. doi:10.1371/journal.pone.0103520. ISSN 1932-6203. PMC 4113456. PMID 25068582.
  7. ↑ "Biased Ligands - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2020-12-08.
  8. ↑ Noda, K.; Feng, Y. H.; Liu, X. P.; Saad, Y.; Husain, A.; Karnik, S. S. (1996-12-24). "The active state of the AT1 angiotensin receptor is generated by angiotensin II induction". Biochemistry. 35 (51): 16435–16442. doi:10.1021/bi961593m. ISSN 0006-2960. PMID 8987975.
  9. ↑ Unal, Hamiyet; Karnik, Sadashiva S. (2014-01-01), Tao, Ya-Xiong (ed.), "Chapter Six - Constitutive Activity in the Angiotensin II Type 1 Receptor: Discovery and Applications", Advances in Pharmacology, Pharmacology & Therapeutics of Constitutively Active Receptors, Academic Press, vol. 70, pp. 155–174, doi:10.1016/b978-0-12-417197-8.00006-7, PMC 7500102, PMID 24931196
  10. 1 2 Singh, Khuraijam Dhanachandra; Unal, Hamiyet; Desnoyer, Russell; Karnik, Sadashiva S. (2018). "Divergent Spatiotemporal Interaction of Angiotensin Receptor Blocking Drugs with Angiotensin Type 1 Receptor". Journal of Chemical Information and Modeling. 58 (1): 182–193. doi:10.1021/acs.jcim.7b00424. ISSN 1549-960X. PMC 6058968. PMID 29195045.
  11. ↑ Zhang, Haitao; Unal, Hamiyet; Gati, Cornelius; Han, Gye Won; Liu, Wei; Zatsepin, Nadia A.; James, Daniel; Wang, Dingjie; Nelson, Garrett; Weierstall, Uwe; Sawaya, Michael R. (2015). "Structure of the Angiotensin Receptor Revealed by Serial Femtosecond Crystallography". Cell. 161 (4): 833–844. doi:10.1016/j.cell.2015.04.011. ISSN 0092-8674. PMC 4427029. PMID 25913193.
  12. ↑ Zanaty, Mario; Seara, Fernando A. C.; Nakagawa, Pablo; Deng, Guorui; Mathieu, Natalia M.; Balapattabi, Kirthikaa; Karnik, Sadashiva S.; Grobe, Justin L.; Sigmund, Curt D. (2020-11-30). "β-Arrestin-Biased Agonist Targeting the Brain AT1R (Angiotensin II Type 1 Receptor) Increases Aversion to Saline and Lowers Blood Pressure in Deoxycorticosterone Acetate-Salt Hypertension". Hypertension. 77 (2): 420–431. doi:10.1161/HYPERTENSIONAHA.120.15793. ISSN 1524-4563. PMC 7855825. PMID 33249862.
  13. ↑ Unal, Hamiyet; Jagannathan, Rajaganapathi; Bhatnagar, Anushree; Tirupula, Kalyan; Desnoyer, Russell; Karnik, Sadashiva S. (2013-01-04). "Long Range Effect of Mutations on Specific Conformational Changes in the Extracellular Loop 2 of Angiotensin II Type 1 Receptor". Journal of Biological Chemistry. 288 (1): 540–551. doi:10.1074/jbc.M112.392514. ISSN 0021-9258. PMC 3537051. PMID 23139413.
  14. ↑ Karnik, S; Gogonea, C; Patil, S; Saad, Y; Takezako, T (November 2003). "Activation of G-protein-coupled receptors: a common molecular mechanism". Trends in Endocrinology and Metabolism. 14 (9): 431–437. doi:10.1016/j.tem.2003.09.007. PMID 14580763. S2CID 6956555.
  15. ↑ "Speaker Biographies". Drug Discovery Chemistry. Retrieved 2020-12-08.
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