Accelerating Breakthrough Discoveries into Medicines

2014 ADDF Harrington Scholars

Thota Ganesh, Ph.D.

Thota Ganesh, PHD

Thota Ganesh, PhD is Associate Professor, Department of Pharmacology, at Emory University, Atlanta, Georgia. Dr. Ganesh obtained his MSc and PhD degrees from Osmania University, Hyderabad, India, and did his postdoctoral studies at IIT-Bombay, India; University of Durham, UK; and Virginia Tech, USA.

Dr. Ganesh’s current research focuses on developing small molecule agents to mitigate the inflammatory pathologies in neurodegenerative diseases, including epilepsy and Alzheimer’s disease (AD).

Alzheimer’s disease is a leading cause of dementia in the elderly. Currently about 4.5 million Americans are living with AD, and the number is expected to triple by the year 2050, yet there is no therapy available to block the inevitable cognitive decline from the disease.

The prostanoid EP2 receptor is emerging as a novel biological target promoting inflammation and subsequent neuropathology in a variety of neurodegenerative disease models including AD. In vitro and in vivo studies from EP2 knockout models show that chronic activation of EP2 in the brain exacerbates AD pathology. However, no tests have been done by pharmacological inhibition of this receptor in vivo to advance EP2 receptor as a druggable target, due to lack of available EP2 antagonists. Dr. Lin recently created a class of highly potent, selective antagonists for EP and demonstrated that a lead EP2 antagonist suppresses the inflammation, and neurodegeneration in a model of epilepsy. This has poised the molecule for testing in models of AD and further optimization.

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C. Glenn Lin, PhD

Chien-Liang Glenn Lin, PHD

Chien-Liang Glenn Lin, PhD is Associate Professor of Neuroscience at The Ohio State University, Columbus, Ohio. Dr. Lin completed his doctorate in Molecular Biology and Biochemistry at the Johns Hopkins University in 1995 and performed postdoctoral research in the Department of Neurology at the Johns Hopkins University. Dr. Lin has published numerous papers in major journals and holds four patents. His recent research focuses on studying the role of glial glutamate transporters EAAT2 in the regulation of synaptic function and plasticity and developing the EAAT2 translational activators for therapeutic application.

The glutamate transporter EAAT2 is primarily localized in peri-synaptic processes of astrocytes closely associated with excitatory synaptic contacts and plays a critical role in the maintenance of low extracellular glutamate levels. Recent investigation into whether restored EAAT2 protein levels and function could ameliorate AD-like behavior and pathology demonstrated that restored EAAT2 function significantly improved cognitive functions, restored synaptic integrity, and reduced amyloid plaques.

Loss of EAAT2 in AD is most likely due to down-regulation of EAAT2 expression at the translational level as a consequence of synaptic loss/ dysfunction. Reactivating EAAT2 translation restores synaptic plasticity and function, and the observed benefits were sustained one month following treatment cessation, indicating that a compound that restores EAAT2 function would be a potential disease modifier.

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