Professor
Unit: Drug Discovery and Development
Auburn University
Harrison College of Pharmacy
255 Pharmacy Research Building
Auburn, AL 36849
Email: rha0003@auburn.edu
Phone: 334-844-8295
Fax: 334-844-8331
1991-99: Research Assistant, Kresge Eye Institute, Wayne State University
2004-05: Associate Investigator, Cardiometabolic & Heart Failure Center, John D. Dingell VA Medical Center
2005-08: Research Associate Fellow, Center of Integrative Medicine and Endocrine Research, Pfizer
2009-present: Assistant/Associate Professor/Professor, Department of Drug Discovery and Development, Auburn University Harrison College of Pharmacy
Overview: The Amin lab seeks to translate their understanding of metabolism into novel effective therapeutics for diseases associated with metabolic dysfunction. Our lab is similar to a small biotechnology company and is based upon experiences and knowledge from my postdoc research at Pfizer and my graduate work in Pharmacology and Medicinal Chemistry at Wayne State University. My lab currently develops novel chemical tools for better understanding how modulation of nuclear receptors can influence metabolically related diseases. This includes neurodegenerative diseases (Alzheimer’s Disease), liver disease (NAFLD –NASH), and cardiometabolic diseases.
Our lab focuses upon novel target identification, rational drug library development based upon machine-based learning, and in silico development using Schroedinger and Gastroplus-based platforms. We synthesize lead compounds and test in vitro using platforms for furthering our understanding for identification of our lead compound. Our lead compounds are then tested in transagenic animal models for efficacy, ADME and toxicity. Additional analysis for metabalomics, lipidomics and changes in gene expression patterns help better understand the impact of our chemical tools on modulation of nuclear receptors. Single cell changes or FRET anaylsis is accomplished by confocal laser microscopy. Animal imaging is accomplished by ECHO and MRI analysis.
Alzheimer’s Disease: We have designed and developed libraries of novel agonists for nuclear receptors including dual PPAR-delta/PPAR-gamma agonists and Liver X-Receptor (LXR-beta) agonists. The design of our compounds is based upon activation and avoidance of avoidance of selective amino acids in the ligand binding domains. One library is based upon design of Peroxisomal Proliferator Activating Receptors (delta, gamma and alpha) (PPARs). Our lead compound is now in phase 2 investigation and will be submitted for a PRE-IND to the FDA in the upcoming future. Another set of compounds is directed towards the design and development of Liver X Receptor-Beta (LXR-beta) agonism, for investigating cholesterol modulation in Alzheimer’s disease. These compounds are geared towards better understanding the significance of cholesterol modulation in ApoE 3 and ApoE4 patients for altering pathologies associated with neurodegeneration.
Liver Disease: Liver disease including fatty liver disease and progression towards liver fibrosis is at epidemic proportions today. We have developed a novel series of LXR-beta compounds and PPAR compounds with highly effective delivery systems of our compounds for stellate cell targeting in fatty liver and Nonalcoholic Steatotic hepatitis (NASH). These delivery systmes include nanoparticle delivery as well as novel hinge systems with mannose or chondroitin sulfate for targeting hepatic inflammatory cells and stellate cells. Our compounds have been designed for preventing the progression of fatty liver disease to liver fibrosis. We use diabetic / obese animal models that devlop liver fibrosis for testing our drug compounds.
Cross talk between Gut-liver and brain: Currently our lab is investigating how the microbiome from patients with diabetes obesity produces chemical signals that can promote neuroinflammation and progress deficits in neuronal function as well as memory impairment. Further work in our lab has developed novel inhibitors of liver enzymes that produce these proatherogenic and neuroinflammatory agents.