Santhoshkumar Puttur, PhD

Puttur

Ophthalmology

Associate Research Professor

Academic Information

Associate Research Professor

Research Interests

  • Crystallin structure and function
  • Lens proteases and proteostasis
  • Minichaperone therapeutics
  • Epigenetics and fibrosis
  • Lens Aging
  • Protein aggregation diseases

Areas of Expertise

  • Protein aggregation and stability
  • Protein interactions and cross-linking
  • Mass spectrometry
  • Multi-angle light scattering
  • Cell culture and cloning
  • Transgenic mice
  • Peptide therapy

Education & Training

Medical School

Mangalore University, Mangalore, India

Awards & Honors

  • 1990: Gold Medal for securing First Rank in M.Sc.
  • 1990: Junior Research Fellowship and Lectureship Award, University Grants Commission, India
  • 1993: Senior Research Fellowship Award, Council of Scientific and Industrial Research, India
  • 1997: Research Associate, Council of Scientific and Industrial Research, India
  • 2005: Frederick A. Bettelheim Travel Award, to attend U.S.–Japan CCRG meeting in Kona, Ha., National Foundation for Eye Research, Rochester, Minn.
  • 2005: Best Application Note Award, Wyatt Technology Corporation
  • 2007: Young Investigator Award, Association of Clinical Biochemists of India
  • 2013-2016: Member, School of Medicine Research Council

Publications

  • Santhoshkumar P. and Shivanandappa, T. (1994). Differential in vivo inhibition of the foetal and maternal brain acetylcholinesterase by bromophos in the rat. Neurotoxicol. Teratol. 16: 227-232
  • Santhoshkumar P., Karanth, S. and Shivanandappa, T. (1995). Pattern of inhibition of acetylcholinesterase in different regions of the brain by two organophosphorus homologues, in relation to their differential neurotoxicity. In: Enzymes of cholinesterase Family (D.M.quinn, A.S. Balasubramanian, B.P. Doctor and P.Taylor Eds.) pp 392-393, Plenum Press , New York.
  • Santhoshkumar P. and Hegde, S.N.  (1995). Incubation-Associate changes in the crop of pigeons (Columbia livia). PAVO 33:145-149.
  • Santhoshkumar P., Karanth, S. and Shivanandappa, T. (1996). Neurotoxicity and pattern of acetylcholinesterase inhibition in the brain regions of the rat by bromophos and ethyl bromophos. Fundam. Appl. Toxicol. 32: 23-30.
  • Santhoshkumar P. and Shivanandappa, T. (1999). In vitro sequestration of two organophosphorus homologs by the rat liver. Chem-Biol. Interact. 119-120:  277-282.
  • Santhoshkumar P. and Sharma,K. K. (2001). Analysis of a-crystallin chaperone function using restriction enzymes and citrate synthase. Mol. Vis. 7: 172-177.
  • Santhoshkumar P. and Sharma,K. K. (2001). Phe71 is essential for chaperone-like function in a-crystallin. J. Biol.Chem. 276: 47094-47099.
  • Srinivas V, Santhoshkumar P, Sharma KK (2002) Effect of trifluoroethanol on the structural and functional properties of alpha-crystallin. J Protein Chem 21: 87-95.
  • Santhoshkumar P. and Sharma,K. K. (2002). Identification of a region in alcohol dehydrogenase that binds to a-crystallin during chaperone action. Biochem. Biophys. Acta. 1598: 115-121.
  • Bhattacharyya J, Santhoshkumar P, Sharma KK (2003) A peptide sequence-YSGVCHTDLHAWHGDWPLPVK [40-60]-in yeast alcohol dehydrogenase prevents the aggregation of denatured substrate proteins. Biochem Biophys Res Commun 307: 1-7.
  • Santhoshkumar P. and Sharma, K. K. (2004). Inhibition of amyloid fibrillogenesis and toxicity by a peptide chaperone derived from alpha A crystallin. Mol. Cell. Biochem. 267: 147-155
  • Sreelakshmi, Y., Santhoshkumar P., Bhattacharyya, J and Sharma, K.K. (2004).  Alpha A-crystallin interacting surfaces of small heat shock protein, Alpha B-crystallin. Biochemistry 43: 15785-15795. PMID: 15595834
  • Biswas A, Miller A, Oya-Ito T, Santhoshkumar P, Bhat M, Nagaraj RH. (2006). Effect of site-directed mutagenesis of methylglyoxal-modifiable arginine residues on the structure and chaperone function of human alphaA-crystallin. Biochemistry 45:4569-4577. PMID: 16584192; PMCID: PMC2597574
  • Santhoshkumar P. and Sharma, K. K. (2006).  Conserved F84 and P86 residues in alphaB-crystallin are essential to effectively prevent the aggregation of substrate proteins. Protein Sci. 15:2488-2498. PMID: 17075130; PMCID: PMC2242417
  • Biswas A, Goshe J, Miller A, Santhoshkumar P, Luckey C, Bhat MB, Nagaraj RH. (2007). Paradoxical effects of substitution and deletion mutation of Arg56 on the structure and chaperone function of human alphaB-crystallin. Biochemistry 46:1117-1127. PMID: 17260942
  • Aziz A, Santhoshkumar P, Sharma KK, Abraham EC (2007) Cleavage of the C-terminal serine of human alphaA-crystallin produces alphaA1-172 with increased chaperone activity and oligomeric size. Biochemistry 46: 2510-2519.
  • Bhattacharyya J, Shipova EV, Santhoshkumar P, Sharma KK, Ortwerth BJ (2007) Effect of a single AGE modification on the structure and chaperone activity of human alphaB-crystallin. Biochemistry 46: 14682-14692.
  • Murugesan R, Santhoshkumar P and Sharma KK (2007).  Cataract-causing aAG98R mutant shows substrate-dependent chaperone activity.  Mol. Vis. 13:  2301-2309. PMID: 18199971
  • Santhoshkumar P, Udupa P, Murugesan R and Sharma KK (2008).  Significance of interactions of low molecular weight crystallin fragments in lens aging and cataract formation. J. Biol. Chem. 283: 8477-8485 PMID: 18227073; PMCID: PMC2417163
  • Rao G, Santhoshkumar P, Sharma KK. (2008) Anti-chaperone betaA3/A1(102-117) peptide interacting sites in human alphaB-crystallin. Mol Vis. 14: 666-674. PMID: 18401461; PMCID: PMC2291074.
  • Murugesan R, Santhoshkumar P, Sharma KK. (2008)  Role of alphaBI5 and alphaBT162 residues in subunit interaction during oligomerization of alphaB-crystallin. Mol Vis.14:1835-44. PMID: 18941542; PMCID: PMC2568893.
  • Biswas A, Lewis S, Wang B, Miyagi M, Santoshkumar P, Gangadhariah MH, Nagaraj RH. (2008) Chemical modulation of the chaperone function of human alphaA-crystallin. J  Biochem.  144(1):21-32 PMID: 18344542
  • Santhoshkumar P, Murugesan R, Sharma KK. (2009) Deletion of (54)FLRAPSWF(61) Residues Decreases the Oligomeric Size and Enhances the Chaperone Function of alphaB-Crystallin. Biochemistry. 48(23):5066-73.PMID: 19388699
  • Pasupuleti N, Gangadhariah M, Padmanabha S, Santhoshkumar P, Nagaraj RH (2010) The role of the cysteine residue in the chaperone and anti-apoptotic functions of human Hsp27. J Cell Biochem 110: 408-419.
  • Raju M, Santhoshkumar P, Sharma KK (2011) Cataract-causing alphaAG98R-crystallin mutant dissociates into monomers having chaperone activity. Mol Vis 17: 7-15.
  • Raju, M., Santhoshkumar, P., Henzl, T. M., and Sharma, K. K. (2011) Identification and characterization of a copper-binding site in alphaA-crystallin, Free Rad. Biol. Med. 50, 1429-1436.
  • Santhoshkumar, P., Raju, M., and Sharma, K. K. (2011) alphaA-crystallin peptide SDRDKFVIFLDVKHF accumulating in aging lens impairs the function of alpha-crystallin and induces lens protein aggregation, PloS one 6, e19291.
  • Kore, R., Hedges, R. A., Oonthonpan, L., Santhoshkumar, P., Sharma, K. K., and Abraham, E. C. (2012) Quaternary structural parameters of the congenital cataract causing mutants of alphaA-crystallin, Mol. Cell .Biochem. 362, 93-102.
  • Nagaraj, R. H., Nahomi, R. B., Shanthakumar, S., Linetsky, M., Padmanabha, S., Pasupuleti, N., Wang, B., Santhoshkumar, P., Panda, A. K., and Biswas, A. (2012) Acetylation of alphaA-crystallin in the human lens: effects on structure and chaperone function, Biochim. Biophys. Acta 1822, 120-129.
  • Nagaraj, R. H., Panda, A. K., Shanthakumar, S., Santhoshkumar, P., Pasupuleti, N., Wang, B., and Biswas, A. (2012) Hydroimidazolone modification of the conserved Arg12 in small heat shock proteins: studies on the structure and chaperone function using mutant mimics, PloS one 7, e30257.
  • Raju, M., Santhoshkumar, P., and Sharma, K. K. (2012) alphaA-Crystallin-derived mini-chaperone modulates stability and function of cataract causing alphaAG98R-crystallin, PloS one 7, e44077.
  • Hariharapura, R., Santhoshkumar, P., and Krishna Sharma, K. (2013) Profiling of lens protease involved in generation of alphaA-66-80 crystallin peptide using an internally quenched protease substrate, Exp. Eye Res. 109, 51-59. doi: 10.1016/j.exer.2013.01.016. PMID: 23410823
  • Nahomi, R. B., Wang, B., Raghavan, C. T., Voss, O., Doseff, A. I., Santhoshkumar, P., and Nagaraj, R. H. (2013) Chaperone Peptides of alpha-Crystallin Inhibit Epithelial Cell Apoptosis, Protein Insolubilization, and Opacification in Experimental Cataracts, J. Biol. Chem. 288, 13022-13035. doi: 10.1074/jbc.M112.440214. PMID: 23508955
  • Kannan, R., Santhoshkumar, P., Mooney, B. P., and Sharma, K. K. (2013) The alphaA66-80 Peptide Interacts with Soluble alpha-Crystallin and Induces Its Aggregation and Precipitation: A Contribution to Age-Related Cataract Formation, Biochemistry 52, 3638-50. doi: 10.1021/bi301662w. PMID: 23631441 PMID: 23631441.
  • Kannan, R., Santhoshkumar, P., Mooney, B. P., and Sharma, K. K. (2013) Identification of Subunit-Subunit Interaction Sites in alphaA-WT Crystallin and Mutant alphaA-G98R Crystallin Using Isotope-Labeled Cross-Linker and Mass Spectrometry, PloS one 8, e65610. doi: 10.1371/journal.pone.0065610. Print 2013. PMID: 23755258
  • Nahomi, R.B., Huang, R., Nandi, S.K., Wang, B., Padmanabha, S., Santhoshkumar, P., Filipek, S., Biswas, A., Nagaraj, R.H. (2013) Acetylation of lysine 92 improves the chaperone and anti-apoptotic activities of human αb-crystallin Biochemistry 52, 8126-8138. doi: 10.1021/bi400638s. PMID: 24128140
  • Santhoshkumar, P., Xie, L., Raju, M., Reneker, L., Sharma, K.K. (2014) Lens crystallin modifications and cataract in transgenic mice overexpressing acylpeptide hydrolase J. Biol Chem. 289, 9039-9052. doi: 10.1074/jbc.M113.510677. PMID: 24554718
  • Raju M, Santhoshkumar P, Xie L, Sharma KK. (2014) Addition of αA-Crystallin Sequence 164-173 to a Mini-Chaperone DFVIFLDVKHFSPEDLT Alters the Conformation but Not the Chaperone-like Activity. Biochemistry 53, 2615-23. doi: 10.1021/bi4017268. PMID: 24697516
  • Santhoshkumar, P., Xie, L., Reneker, L., Sharma, K.K. (2014).  Histone Deacetylase Inhibitors Trichostatin A and Vorinostat Inhibit TGFβ2-Induced Lens Epithelial-to-Mesenchymal Cell Transition. Invest Ophthalmol Vis Sci. 55, 4731-40. doi: 10.1167/iovs.14-14109. PMID: 24994865.
  • Raju, M., Santhoshkumar, P. and Sharma, K.K. (2016). Lens Endogenous Peptide αA66-80 Generates Hydrogen Peroxide and Induces Cell Apoptosis. Aging  Dis.http://dx.doi.org/10.14336/AD.2016.0805
  • Santhoshkumar, P., Karmakar, S and Sharma K. (2016). Structural and Functional Consequences of Chaperone Site Deletion in αA-Crystallin.  Biochim. Biophys. Acta. 1864(11):1529-38. Doi 10.1016/j.bbapap.2016.08.006. PMID: 27524665

Review articles

  • Sharma KK, Santhoshkumar P. (2009) Lens aging: effects of crystallins. Biochim Biophys Acta. 90(10):1095-108. PMID: 19463898
  • Raju M, Santhoshkumar P, Krishna Sharma K. (2016) Alpha-crystallin-derived peptides as therapeutic chaperones. Biochim Biophys Acta. 1860:246-51. doi: 10.1016/j.bbagen.2015.06.010.

Book Chapters

  • Santhoshkumar P., Kannan, R. and Sharma, K.K.  (2015)  In book: Studies on the Cornea and Lens: Oxidative Stress in Applied Basic Research and Clinical Practice, Chapter: Proteases in Lens and Cataract, Publisher: Springer New York, Editors: Mark A. Babizhayev, David Wan-Cheng Li, Anne Kasus-Jacobi, Lepša Žorić, Jorge L. Alió, pp.221-238.   DOI: 10.1007/978-1-4939-1935-2_13 .