Chinnaswamy Kasinathan

My research involves the effects of tyrosine sulfation, a post-translational modification, on the secretion and biological activities of salivary proteins are being investigated. Additional research investigates the biochemical mechanism leading to alcoholism. Currently, our attention is directed in developing a sustained injectable drug for the treatment of narcotic drug addiction using the "Gel Depot" system, which can eliminate current limitations. Gel Depot is a novel, non-toxic, poly (ethylene glycol) based hydrogel system that is injected subcutaneously. "Gel Depot" system is also being used to sequester beta-amyloid (Aβ) peptides that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease (AD). Alzheimer's disease is closely linked with aging and diabetes, consistent with the term ‘Type III diabetes’ for AD. Aβ pathology has almost exclusively studied in genetically engineered mice/rats, which normally encode/generate non-human-sequence Aβ peptides. Unfortunately, mouse/rat artificial human AβPP Tg expression bypasses physiological disease processes of aging and diabetes. The diabetes model we developed in white rabbits, which normally encodes/generates human-sequence Aβ system-wide and also demonstrates robust Aβ pathology in brain in 15 weeks after initiating uncontrolled diabetes/hyperglycemia. This animal model is being used to study major neurodegenerative disease proteins in serum and/or saliva, which can provide key biomarker information.

BS, Chemistry, University of Madras, India

MS, Biochemistry, University of Madras, India

PhD, Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India

1. Neurodegenerative disease biomarkers. Salivary Biomarkers for Amyloid Pathology. Alzheimer's disease (AD) is the most common cause of dementia with no easy and effective diagnostic methods for use in the early stages of cognitive impairment. Our aim is to explore and identify effective biomarkers for confident early diagnosis of AD β-amyloid pathology.
2. Detox Gel to treat Alzheimer’s Disease. Alzheimer's disease (AD) is believed to result from the neurotoxic effects of beta-amyloid peptide Aβ42 and Aβ40. These peptides aggregate into beta-sheet structures, which are observed as plaques at autopsy. According to the "peripheral sink" hypothesis, these neurotoxic peptides can cross the blood-brain barrier and therefore be removed from the central nervous system by injection into the bloodstream of a substance that specifically binds Aβ40/42. We have designed PEGylated retro-inverso (RI) peptide, ffvlk, of the native sequence KLVFF, which demonstrated these required properties.

1. Frederikse P, Kasinathan C. Lens Biology is a Dimension of Neurobiology. Neurochem Res. 2017 Apr;42(4):933-942.
2. Frederikse PH, Nandanoor A, Kasinathan C. Fragile X Syndrome FMRP Co-localizes with Regulatory Targets PSD-95, GABA Receptors, CaMKIIa, and mGluR5 at Fiber Cell Membranes in the Eye Lens. Neurochem Res. 2015 Nov;40(11):2167-76.
3. Frederikse PH, Kasinathan C. Lens GABA receptors are a target of GABA-related agonists that mitigate experimental myopia. Med Hypotheses. 2015 Jun;84(6):589-92.
4. Frederikse PH, Nandanoor A, Kasinathan C. "Moonlighting" GAPDH Protein Localizes with AMPA Receptor GluA2 and L1 Axonal Cell Adhesion Molecule at Fiber Cell Borders in the Lens. Curr Eye Res. 2016;41(1):41-9.
5. Gupta A, Espinosa V, Galusha LE, Rahimian V, Miro KL, Rivera-Medina A, Kasinathan C, Capitle E, Aguila HA, Kachlany SC. Expression and targeting of lymphocyte function-associated antigen 1 (LFA-1) on white blood cells for treatment of allergic asthma. J Leukoc Biol. 2015 Mar;97(3):439-46.
6. Bhattacharyya M, Nandanoor A, Osman M, Kasinathan C, Frederikse P. NMDA glutamate receptor NR1, NR2A and NR2B expression and NR2B Tyr-1472 phosphorylation in the lens. Neurochem Res. 2014 Sep;39(9):1825-32.
7. Sundaram RK, Kasinathan C, Stein S, Sundaram P. Novel Detox Gel Depot sequesters b-Amyloid Peptides in a mouse model of Alzheimer's Disease. Int J Pept Res Ther. 2012 Jun 1;18(2):99-106.
8. Bitel CL, Kasinathan C, Kaswala RH, Klein WL, Frederikse PH. Amyloid-b and tau pathology of Alzheimer's disease induced by diabetes in a rabbit animal model. J Alzheimers Dis. 2012;32(2):291-305.
9. Sundaram RK, Kasinathan C, Stein S, Sundaram P. Detoxification depot for beta-amyloid peptides. Curr Alzheimer Res. 2008 Feb;5(1):26-32.
10. Jean S, Kasinathan C, Buyske S, Manowitz P. Ethanol decreases rat hepatic arylsulfatase A activity levels. Alcohol Clin Exp Res. 2006 Nov;30(11):1950-5.
11. Kasinathan C, Jean S, Manowitz P. Tyrosine sulfation of arylsulfatase A and its peptide. Protein Pept Lett. 2006;13(4):357-61.
12. Kasinathan C, Vrana K, Beretta L, Thomas P, Gooch R, Worst T, Walker S, Xu A, Pierre P, Green H, Grant K, Manowitz P. The future of proteomics in the study of alcoholism. Alcohol Clin Exp Res. 2004 Feb;28(2):228-32.
13. Kasinathan C, Jean S, Manowitz P. Tyrosine sulfation of arylsulfatase A and its peptide. Protein Pept Lett. 2006;13(4):357-61.
14. Ramaprasad P, Kasinathan C. In vivo induction of tyrosylprotein sulfotransferase by ethanol: role of increased enzyme synthesis. Alcohol Clin Exp Res. 1998 Aug;22(5):1120-4.
15. Kasinathan C, Ramaprasad P, William S, Espina N. Stimulation of tyrosylprotein sulfotransferase activity by ethanol: role of increased enzyme level. Alcohol. 1998 May;15(4):271-6.