Fall 2018 Asa Gray Seminars
September 10th, 2018
Brandee Rockefeller, Ph. D., Associate Professor of Biology, Utica College, Utica, NY.
The Role of PI3K/mTOR in Vascular Morphogenesis
Angiogenesis, the formation of blood vessels from preexisting vasculature, is a highly coordinated and tightly regulated physiological process requiring endothelial cells to respond to environmental cues proliferate, migrate, and differentiate. The PI3K signaling cascade is essential to proper formation and function of these vascular networks, controlling several key aspects of angiogenesis. Dysfunctional angiogenesis, such as that seen in vascular malformations is directly linked to genetic aberrations in several genes along the PI3K pathway. Characteristics unique to vascular malformations are also associated with the vasculature in numerous other pathologies including cardiovascular disease, cancer, retinopathy, chronic wounds, and diabetes all of which cause significant morbidity and mortality. Therefore, understanding the mechanistic basis governing the formation and maintenance of vascular malformations may provide insight for therapeutic inventions across a wide range of diseases. Interestingly, small case studies of vascular malformations treated with rapamycin, an mTORc1 inhibitor, have shown clinical improvement, however the rationale and mechanism were not well understood. In vitro, ex vivo, and in vivo models of vascular malformations across two complementary genetic drivers, all show rapamycin sensitivity. Additionally, utilizing these models we have found mTORc1 signaling is a critical regulator of ENOS activation, endothelial fate decisions, and a driver for vascular malformations by disrupting normal tip/stalk selection and inducing metabolic reprogramming. Collectively, this data supports the use of rapamycin as a therapeutic intervention for PI3K driven vascular malformations and provides insight that metabolic targets may also be useful.
September 24th, 2018
Lucas J. Tucker, Ph.D., Associate Professor of Chemistry and Biochemistry, Director of the Siena College Green Chemistry Institute, Siena College, Albany, New York.
Green Chemistry: If we don’t make the change, who will?
Methods for developing sustainable practice within chemistry will have a large impact on the future of the field. Reaching students that will study all fields and take jobs in all sectors during their secondary education can result in not only progressive scientists, but also executives to hire them and fund their work. As such, in collaboration with dozens of New York state high school teachers a series of green laboratory experiments have been developed and made available. A discussion of green chemistry, research at Siena, consulting for companies both large and small, and pedagogical work will paint a picture of the scientific life of one chemist from a small town in upstate NY.
October 22nd, 2018
James L. Hougland, Ph.D., Associate Professor of Chemistry, Syracuse University, Syracuse, NY
Ghrelin acylation by ghrelin O-acyltransferase: Unique chemistry leading to unique biological function
Ghrelin is a peptide hormone involved in appetite stimulation, energy balance regulation, glucose homeostasis, and a range of other physiological and neurological pathways. Ghrelin requires octanoylation of a serine side chain, a unique posttranslational modification within the human proteome, to bind its cognate receptor and activate signaling. The enzyme that catalyzes this acylation, ghrelin O-acyltransferase (GOAT), was identified in 2008 as a member of the membrane-bound O-acyltransferase (MBOAT) enzyme superfamily. Ghrelin is the only predicted substrate for GOAT, suggesting that blocking ghrelin acylation using GOAT inhibitors potentially offers a specific and targeted therapeutic avenue to treat conditions impacted by ghrelin signaling.
We are applying chemical, biochemical, and computational approaches to investigate ghrelin acylation by human GOAT (hGOAT). Using structure-activity analysis of substrates and inhibitors, we’ve identified multiple functional groups within ghrelin recognized by hGOAT. Small molecule hGOAT inhibitors have revealed hGOAT contains a functionally essential cysteine residue, providing a chemical avenue for locating domains within hGOAT required for enzyme activity. Defining the hGOAT active site and substrate binding sites through computational and biochemical analyses offers insight into the structure of this integral membrane acyltransferase and related enzymes while providing guidance for designing and optimizing hGOAT inhibitors.
November 12th, 2018
Dan Kurtz, Ph.D., Professor of Biology, Utica College, Utica, New York.
Perireceptor events in olfaction
Abstract TBA