Biography
editRajendra Kumar Sharma SOM, PhD, DSc, FRSA son of late Venkateswar Sharma and Durga Devi Sharma was born on January 2, 1942 among two brothers and two sisters in Hathras, UP, India. He spent his childhood in this small town and went to Mohan Gunj Primary Municipality School; high school and intermediate from the Shri Saraswati Vidyalaya Intermediate College.
Sharma joined the Aligarh Muslim University and completed his B.Sc. in Chemistry, Botany and Zoology and M.Sc. in Biochemistry. Due to the shortage of chemistry and physics teachers at that time, he decided to serve as a chemistry lecturer at the Shri Saraswati Vidyalaya Intermediate College, Hathras. Later, he was awarded a research fellowship from the Council of Scientific and Industrial Research for a Ph.D. in Biochemistry at the All India Institute of Medical Sciences, New Delhi which is considered the Harvard of Asia, under the supervision of Dr. Rajarshi Mazumder who joined the institute after completing his postdoctoral fellowship training under the supervision of Dr. Severo Ochao who was awarded Nobel Prize in Physiology and Medicine in 1959 from the USA and Dr. Gursaran Prasad Talwar, Padma Bhushan. His thesis work was published in the prestigious journal - J Biol Chem (1970) 245, 3008-3014. He served as a lecturer after completing his Ph.D. in the Department of Biochemistry, Lady Hardinge Medical College & Hospital, New Delhi.
Sharma married in 1970 to Manjul Saraswat and has three daughters Priya, Puja and Poonam who are married to Pradeep Sharma, Suneel Sharma and Anil Sharma, respectively. He is blessed with six beautiful grandchildren, Aarika, Jiya, Iraj, Sanvi, Aaryan and Avani.
Moving Around in North America
editSharma was awarded a postdoctoral fellowship from the U. S. National Science Foundation to carry out further research in cancer biology field under the supervision of Dr. Roy L. Kisliuk and he joined the Department of Biochemistry & Pharmacology in 1972, Tufts University School of Medicine, Boston, Massachusetts, USA. Later he joined the Department of Biochemistry, College of Medicine, University of South Alabama, Mobile, Alabama, USA. However, Sharma was unable to acquire green card for the USA therefore, he moved to Canada in 1976.
Sharma joined the Department of Biochemistry, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. He decided to moved to India in 1978 with his family in search for an academic position. However, he could not find a job in his chosen field, then he decided to move back to Canada again in 1979. He is very proud of his Indian roots and heritage, he frequently visits to India. He is a respected mentor to many Indian and international scientists. Sharma is an individual of an unbelievable stature. He joined the Department of Biochemistry, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba in 1979. Later he moved to the Department of Medical Biochemistry, University of Calgary, Calgary, Alberta, Canada. He made several milestone discoveries at the University of Manitoba and the University of Calgary in the area of signal transduction.
Sharma moved to the University of Saskatchewan in 1991 and joined the Department of Pathology & Laboratory of Medicine, College of Medicine. At present, he is a Distinguished Professor and holds Associate Memberships in the Departments of Medicine and Surgery.
Scientific Career
editSharma has gained an international reputation over the last 44 years for innovations and original procedures in widely disparate areas, involving enzymology and signal transduction, in the areas of the cardiovascular system, brain and cancer research. His laboratory is one of the pioneer laboratories in the area of calmodulin-regulated systems and myristoylation of cellular proteins. He has made several milestone discoveries and his research over the last 44 years has reflected “cutting edge” discoveries in the areas of colorectal cancer and the cardiovascular system as a whole. Of note, the discovery of the role of lipid modification in Sharma’s laboratory is likely to lead to early diagnosis and treatment of colorectal cancer. He has worked with many great scientists, collaborators, post-doctoral fellows, student and assistants.
To date, he has published 241 full-length papers in reputed journals (197 refereed papers and 44 book chapters, for details, see PubMed-NCBI). In addition, he has published 154 abstracts at national and international scientific meetings. Sharma is the co-editor of a book on Signal Transduction Mechanisms for Kluwer Academic Publishers (Dordrecht/Boston/London)[1] and currently, he is in the process of editing two books in the area of cancer and the cardiovascular system. Sharma’s extensive expertise in areas involving enzymology and signal transduction has led him to purifying and characterizing close to two dozen proteins from various species[2][3]. Through purification of these proteins he discovered, purified and characterized several new proteins (i.e. activators and inhibitors) and established their biological and physiological functions[4][5].
Calmodulin-Regulated Systems
editSharma has a longstanding research interest in the area of biochemical mechanisms of the signal transduction processes, with special emphasis on Ca2+ calmodulin (CaM)-regulated enzymes and their involvement in the regulation of both cAMP and Ca2+ second messenger systems. His main focus has been on the regulation of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE). This research has contributed significantly to the discovery of CaMPDE isozymes, the delineation of the molecular, catalytic and regulatory properties of the isozymes and the elucidation of the physiological and regulatory significance of these isozymes. These isozymes are regulated by multiple second messenger-dependent regulatory systems. For each of the isozymes, he has proposed a working hypothesis describing how the multiple regulatory activities interact with each other to achieve regulatory advantages in controlling cAMP metabolism in the cell during cell activation[6][7][8]. One of the main features of the hypothesis is that during cell activation, the various regulatory activities are temporally separated. The result suggests that a temporal separation of second messenger-dependent reactions can be conceived as a natural consequence of dynamic fluxes of the messengers.
He discovered a protein, high molecular weight [calmodulin-binding protein (HMWCaMBP)][9] and subsequently it was established that HMWCaMBP is homologous to calpastatin which inhibits calpains enzymes[10]. He established role of HMWCaMBP in ischemia and reperfusion in primary murine cardiomyocyte cultures and human cardiac ischemia[11][12].
Myristoylation of Cellular Proteins
editSharma has later developed a research interest in the role of spatial separation of regulatory activities during the process of signal transduction which has led him to initiate a study on the myristoylation of cellular proteins.
Colorectal cancer, a major health concern in North America and indeed worldwide, has both a high incidence and a high mortality rate. At this time, the treatment of advanced colorectal cancer remains difficult. Sharma has demonstrated for the first time that N-myristoyltransferase (NMT) is more active in colonic epithelial neoplasms than in normal- appearing colonic tissue and that an increase in NMT activity appeared at an early stage in colonic carcinogenesis[13][14]. This study was published in the prestigious J Natl Cancer Inst (1995) 87, 1630-1635. The paper was highlighted in this volume in the Issue Section of the J Natl Cancer Inst 87, 1569 and received wide spread media coverage. NMT is proposed as a novel molecular target for anti-cancer drug design. This work from his laboratory demonstrated a major breakthrough in the pathogenesis of colorectal cancer. These findings suggested that the NMT enzyme might play a significant role in the development of colorectal cancer and help to facilitate the early diagnosis of colon cancer. This innovative research and discoveries will provide a strong foundation for the early diagnosis and treatment of cancer. Therefore, Drs. R.L. Felsted, C.J. Glover and K. Hartman discussed the study on NMT activity in colon cancer in the editorials (J Natl Cancer Inst (1995) 87, 1571-1572). They have stated that studies regarding the increase in NMT activity in colon cancer from Sharma’s laboratory may provide important new information to advance our understanding of cancer. In addition, the National Cancer Institute submitted our report for a news release to the scientific and public media in Bethesda, Maryland in October 1995 in anticipation of the interest it would generate within the scientific community.
Later Sharma has established that altered expression and localization of NMT in the peripheral blood and bone marrow (BM) in colon cancer patients[15]. Furthermore, immunohistochemical analysis revealed weak to negative staining for NMT in peripheral blood mononuclear cells (PBMC) of controls, whereas strong positivity was observed in PBMC colon cancer patients. In addition, NMT was localized mostly in the nuclei of the BM mononuclear cells of the colon cancer patients, whereas NMT remained cytoplasmic in the control bone marrow specimens. This striking difference in NMT expression offers the basis of a potential adjunct investigative tool for screening and/or diagnosis patients at risk for or suspected of having colon cancer. Furthermore, altered localization of NMT in BM of tumor-bearing hosts may serve as an added investigative tool for the therapeutic purpose.
References
edit- ^ Barnes, JA; Coore, HG; Mohammed, AH; Sharma, RK (1995). Signal Transduction Mechanisms. Kluwer Academic Publishers. ISBN 978-1-4613-5833-6.
- ^ Sharma, RK; Desai, R; Waisman, DM; Wang, JH (1979). "Purification and subunits structure of bovine brain modulator binding protein". J Biol Chem (254): 4276–4282. PMID 220236.
- ^ Kumar, S; Sharma, RK (2014). "An improved method and cost effective strategy for soluble expression and purification of human N- myristoyltransferase 1 in E. coli". Mol Cell Biochem (392): 175–86. PMID 24668448.
- ^ King, MJ; Sharma, RK (1993). "Identification, purification and characterization of a membrane-associated N-myristoyl transferase inhibitor protein from bovine brain". Biochem J (291): 635–639. PMID 8484742.
- ^ Sharma, RK; Wirch, E; Wang, JH (1978). "Inhibition of Ca2+ activatable cyclic nucleotide phosphodiesterase reaction by a heat stable inhibitor protein from bovine brain". J Biol Chem (253): 3575–3580. PMID 206547.
- ^ Kakkar, R; Raju, RVS; Sharma, RK (1999). "Calmodulin-dependent cyclic nucleotide phosphodiesterase". Cell Mol Life Sci (55): 1164–1185. PMID 10442095.
- ^ Sharma, RK; Wang, JH (1985). "Differential regulation of bovine brain calmodulin dependent cyclic nucleotide phosphodiesterase isozyme by cyclic AMP-dependent protein kinase and calmodulin-dependent phosphatase". Proc Natl Acad Sci USA (82): 2603–2607. PMID 2986124.
- ^ Sharma, RK; Wang, JH (1986). "Calmodulin and Ca2+-dependent phosphorylation and dephosphorylation of 63-kDa subunit-containing bovine brain calmodulin stimulated cyclic nucleotide phosphodiesterase isozyme". J Biol Chem (261): 1322–1328. PMID 3944089.
- ^ Sharma, RK (1990). "Purification and characterization of novel calmodulin binding protein from cardiac muscle". J Biol Chem (265): 1152–1157. PMID 2295605.
- ^ Kakkar, R; Raju, RVS; Mellgren, RL; Radhi, JM; Sharma, RK (1997). "High molecular weight calmodulin-binding protein contains calpastatin activity". Biochemistry (36): 11550–11555. PMID 9340007.
- ^ Parameswaran, S; Sharma, RK (2014). "Altered expression of calcineurin, calpain, calpastatin and HMWCaMBP in cardiac cells following ischemia and reperfusion". Biochem Biophys Res Commun (443): 604–609. PMID 24333421.
- ^ Parameswaran, S; Sharma, RK (2014). "Ischemia and reperfusion induce differential expression of calpastatin and its homologue high molecular weight calmodulin- binding protein in murine cardiomyocytes". PLoS One (9): e114653.Doi: 10.1371/journal. pone. 0114653.
- ^ Magnuson, B; Raju, RVS; Moyana, TN; Sharma, RK (1995). "Increased N-myristoyl transferase activity observed in rat and human colonic tumors". J Natl Cancer Inst (87): 1630–1635. PMID 7563206.
- ^ Raju, RVS; Moyana, TN; Sharma, RK (1997). "N-myristoyl transferase over-expression in human colorectal adenocarcinomas". Exp Cell Res (235): 145–154. PMID 9281363.
- ^ Shrivastav, A; Varma, S; Saxena, A; DeCoteau, J; Sharma, RK (2007). "N-myristoyltransferase: A novel potential diagnostic tool for colon cancer". J Transl Med (5): 58–63. PMID 18021392.