Dr. Arivalagan Muthusamy, PhD,
Chief Scientist
of Zietchick Research Institute

Dr. Arivalagan Muthusamy, the Chief Scientist at Zietchick Research Institute,  is  a results-oriented senior scientist with more than 2 decades of experience in biochemistry, glycobiology, immunology and retinal vascular biology. .For 6 years, he was employed as a Research Investigator at the University of Michigan Kellogg Eye Center. During that time, he was involved in planning and executing major research projects in diabetic retinopathy utilizing cellular & molecular and vascular biology methods. Diabetic retinopathy is a VEGF-associated retinopathy.  His work has included the analysis of pathological changes in the diabetic retina of both rat and mouse models. His research findings have been published in high tier journals and he has delivered several domestic/international presentations at scientific meetings. In 2016, he was appointed as the Chief Scientist at Zietchick Research Institute, LLC and served as a co-investigator in several NIH-funded studies focused on developing new therapeutics for diabetic retinopathy and retinopathy of prematurity.

Dr. Muthusamy's Contributions to Science: 

 Understanding the molecular mechanisms of VEGF- mediated VEGR2 activation in ischemic reperfusion injury during diabetic complications leading to vascular permeability is very important for identifying the novel therapy for treatment. His study for the first time demonstrated the role of a phosphorylated tight junction protein, occludin, in regulating the retinal vascular permeability in ischemic reperfusion injury model in a VEGFR2 -dependent manner. Results from these studies highly contributes to develop a transgenic mouse in targeting the phosphosite of occludin to block the retinal vascular permeability. These results also prompted his team of colleagues to identify the role of occludin phosphorylation in middle cerebral occlusion (MCAO) -mediated cerebrovascular permeability in an in vivo model. 

a)    Steven F. Abcouwer, Cheng-Mao Lin, Sumathi Shanmugam, Arivalagan Muthusamy, Barber AJ, Antonetti DA. (2013) Minocycline prevents retinal inflammation and vascular permeability following ischemia-reperfusion injury. J Neuroinflammation. 10:149. 

b)    Arivalagan Muthusamy, Cheng-Mao Lin, Sumathi Shanmugam, Heather M. Lindner, Steven A. Abcouwer, David A. Antonetti. (2014) Ischemia-reperfusion injury induces occludin phosphorylation/ubiquitination and retinal vascular permeability in a VEGFR-2-dependent manner. J. Cereb Blood Flow Metab. 34: 522-531.

c)     Yunpeng Du, Megan Cramer, Chieh Allen Lee, Jie Tang, Arivalagan Muthusamy, David A. Antonetti, Hui Jin, Krzysztof Palczewski, Timothy S. Kern. (2015) Adrenergic and serotonin receptors affect retinal superoxide generation in diabetic mice: relationship to capillary degeneration and permeability.FASEB J. 29: 2194-2204.   

d)    Liu H, Tang J, Du Y, Lee CA, Golczak M, Muthusamy A, Antonetti DA, Veenstra AA, Amengual J, Von Lintig J, Palczewski K, Kern TS. (2015) 22. Retinylamine Benefits Early Diabetic Retinopathy in Mice. J Biol Chem. 290: 21568- 21579.

(e) Gonçalves A, Lin CM, Muthusamy A, Fontes-Ribeiro C, Ambrósio AF, Abcouwer SF, Fernandes R, Antonetti DA. (2016) Protective Effect of a GLP-1 Analog on Ischemia-Reperfusion Induced Blood-Retinal Barrier Breakdown and Inflammation. Invest Ophthalmol Vis Sci. 57: 2584-2592.

 He has also explored the role of sulfated proteoglycans in joint diseases including osteoarthritis and rheumatoid arthritis models. Identified the role of heparin sulfated proteoglycan in regulating VEGF-mediated VEGFR2 activation during angiogenesis in an in vitro model system. This study encouraged us to explore the role of human perlecan, heparan sulfated proteoglycan, in synovial angiogenesis during synovial hyperplasia in rheumatoid arthritis.

a)    Arivalagan Muthusamy, Carlton R. Cooper, and Gomes RR, Jr. (2010) Soluble perlecan domain I enhance VEGF165 activity and receptor phosphorylation in human bone marrow endothelial cells. BMC Biochemistry. 11: 43-56.

 Publications in his early research career focused on that localization of a novel class low-sulfated proteoglycan receptor in the human placenta responsible for the adherence of malarial parasite, Plasmodium falciparum leading to maternal malaria. These publications were instrumental in identifying the crucial factors responsible for the host-pathogen interaction during maternal malaria. These studies lead us to find various potential glycosaminoglycan inhibitors of malarial parasite adherence in human placenta.

a)    Arivalagan Muthusamy, Achur RN, Bhavanandan VP, Fouda GC, Taylor DW, and Gowda DC. (2004) Plasmodium falciparum –infected erythrocytes adhere both in the intervillous space and on the villous surface of human placenta by binding to the low-sulfated chondroitin sulfate proteoglycan receptor. American Journal of Pathology, 164: 2013-2025.  (Cover Page Article).

b)    Arivalagan Muthusamy, Achur RN, Valiyaveettil M, Madhunapantula SV, IKakizaki K, Bhavanandan VP, and Gowda DC. (2004) Structural characterization of the bovine tracheal chondroitin sulfate chains and binding of Plasmodium falciparum-infected erythrocytes. Glycobiology, 14: 635-645.  

c)     Arivalagan Muthusamy, Achur RN., Valiyaveettil M, Bhotti JJ, Taylor DW, Leke RF, and Gowda DC. (2007) Chondroitin sulfate proteoglycan but not hyaluronic acid is the receptor for the adherence of Plasmodium falciparum –infected erythrocytes in human placenta and IRBC adherence upregulates the receptor expression.  American Journal of Pathology, 170: 1989-2000.  

d)    Suchi Goel, Arivalagan Muthusamy, Jun Miao, Liwang Cui, Ali Salanti, Elizabeth A. Winzeler, Gowda DC. (2014) Targeted disruption of a ring-infected erythrocyte surface antigen (RESA)-like export protein gene in Plasmodium falciparum confers stable chondroitin 4-sulfate cytoadherence capacity. J. Biol Chem. 289: 34408-34421.