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Biography

Ronald A. Hill, B.S.Chem., Ph.D., is a native of central Ohio. He graduated from the University of Michigan in 1982 with a B.S.Chem. degree, completing an honors thesis project in mechanistic organic chemistry with Professor Peter A. S. Smith. He then spent 4-1/2 years engaged in analytical chemistry and biopharmaceutics R&D at the Upjohn Company in Kalamazoo, MI, followed by graduate study at The Ohio State University, where he completed a Ph.D. in Pharmacy, with emphases in synthetic medicinal and computational chemistry. His graduate research was directed by Professors Duane D. Miller and Jan K. Labanowski (Ohio Supercomputer Ctr.). In 1991, he established a research group at ULM, mainly engaged in areas of synthetic medicinal and bioanalytical chemistry. Historically, his research, funded at various times by the NIH and the AHA, focused mostly on projects related to the central nervous system, particularly the efficient delivery of small organic molecules to the CNS and their distribution, biotransformation, and actions therein. Over the years, he also collaborated extensively with investigators working in areas of pharmaceutics, toxicology, pharmacology, and clinical sciences, and also gained extensive acumen in molecular therapeutics design, molecular biopharmaceutics, and molecular toxicology. His more-recent educational duties at the Ph.D. and Pharm.D. levels, and ongoing research collaborations in areas including cancer and Alzheimer’s disease, has demanded even more breadth and depth of knowledge, especially in areas bridging early discovery science to clinical application. He also currently serves as a member of the Expert Panel for the Cosmetic Ingredient Review, a key safety assessment body for non-drug personal care products. He has served as major adviser for a number of M.S. and Ph.D. students, and on the graduate committees of now more than 60 others, all of whom have an admirable record of accomplishment in industry, government, or academia.

Abstract

Compelling evidence continues to accrue that late-onset (non-familial) Alzheimer’s disease (LOAD), arising early in olfactory structures of the brain, progresses in a spatiotemporally consistent pattern via propogating “inflammaging” processes; predisposing susceptibility may be established as early as gestationally. Genome-wide association studies (GWASs) of cognitively uncompromised individuals who exhibit apparent high pathology suggest that select combinations of genetic attributes can confer resistance to cognitive decline; and, although certain specifics of pathological signatures differ from those in cognitively deteriorating individuals, these might reflect successful defense against an otherwise pathological chain of events. A central player emerging from these GWASs is reelin, a large glycoprotein component of the extracellular matrix (ECM). Though historically regarded mostly as a key player in embryo-fetal development reelin exhibits functional interplay in the adult brain with other molecular constituents having clearly established associations with LOAD, such as apolipoprotein E, and with the responsiveness states of inflammaging-associated cells, notably microglia. The complexities and relative paucity of knowledge regarding ECM maintenance, remodeling, and functional dynamics, and the analytical challenges involved in achieving increased clarity, means that gaining therapeutically actionable traction will be difficult; however, the tantalizing thought that GWASs of these individuals may be showing us ways forward motivates rising to these challenges. Reelin possesses multiple functional domains, and certain reelin fragments exhibit trafficking and function disparate from intact glycoprotein. Very recently, ADAMTS-3 was identified as the catalyst of a proteolytic cleavage of reelin shown to be inactivating in terms of reelin’s canonical activities. Because of reelin remains heavily involved during adulthood in dynamic brain maintenance and remodeling, deleterious consequences can be expected from anatomically untargeted alterations in reelin function. Potential strategies for pathologyactivated, localized generation of suitable modulators will thus be needed, and progress with respect to devising such strategies will be shared in this presentation. Speaker Biography Ronald A Hill is now spanning almost 35 years, over a pharmaceutical sciences career. He has aimed to become a generalist with high-level acumen in relating the Chemistry of biologically active molecules to their interactions with, and actions on, humans and their hosted organisms (normal microbiome, microbial pathogens, parasites). The central focus of his own research has always related to the CNS, guided also by the aim of constantly gaining acumen in molecular therapeutics design, molecular biopharmaceutics, and molecular toxicology and in general, the science of successfully bridging discovery at its earliest stages to clinical application. His educating duties at the PhD and PharmD levels are extensive, and carried out with the underlying hope that the molecular science and molecular design will be intelligently and artfully acted on in clinical practice. His current research collaborations center on neurodegenerative conditions and cancer.

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