This is the first competing renewal application for my RCS Award. My lab has been engaged in the field of eye research for >37 years; I’ve been a tenured full Professor since 1994. Historically, our focus has been on understanding the normal role of cholesterol and related isoprenoid compounds in promoting and preserving the structure and function of the retina. However, more recently (during the RCS Award period), we’ve turned to studies relevant to traumatic injury to the eye and visual system. Eye injuries resulting in compromised or lost vision are among the signature injuries sustained by our Veterans and deployed soldiers engaged in the recent conflicts in Iraq and Afghanistan (OEF, OIF). Currently, about 170,000 Veterans are legally blind, and nearly 1.5 million have some kind of visual deficit that is battle-related. Traumatic brain injury (TBI) is another signature injury of those conflicts; a significant percentage of TBI patients suffer visual deficits, nearly a third of which are blast-induced. My lab’s goal is to understand the molecular and cellular mechanisms underlying these kinds of trauma-induced vision loss, and to find practical pharmacological interventions to prevent or retard their progression. Those studies are funded by an ongoing VA MERIT Award. In addition, we’re investigating a form of retinitis pigmentosa (RP59)— a hereditary progressive blinding disorder— about which little is known, initially in an effort to understand the causes of the associated retinal degeneration at the molecular level and eventually to develop gene therapy approaches to ameliorate or prevent the degeneration and vision loss. Those studies are supported by an ongoing NEI/NIH R01 grant award. I’ve been a VA Research Service staff member at the Buffalo VAMC since July, 2008, and an RCSA recipient since April, 2016. I hold a tenured endowed chair Professorship and am Vice-Chair/Director of Research in the Dept. of Ophthalmology at the affiliated university (SUNY- University at Buffalo (UB)). I am the only person in the history of my department to become a UB Distinguished Professor and a SUNY Distinguished Professor, and I am the sole RCSA recipient at my VA site. Over the years, I’ve been fortunate to have numerous, productive collaborations, both with VA and non-VA researchers, including current, ongoing projects, and have a strong history of extramural grant funding. I’ve authored or coauthored 129 peer-reviewed publications (+2 in press, + 2 under review)— 38% of which have been published since I joined the VA— plus 10 book chapters and 242 conference abstracts. I’ve given 241 invited lectures (120 while on VA staff) at other universities and research institutions, plus 65 platform presentations (15 while on VA staff) at biomedical research conferences, nationally and internationally. I’ve engaged in multiple service activities— to the VA (local and national), my university, and the broader research community— including service on VA, NIH, DOD (CDMRP), and private foundation grant review panels. I also serve on the Scientific Advisory Board of Foundation Fighting Blindness (FFB). I’ve been elected President of the two leading international eye and vision research professional societies (ARVO and ISER), and serve as Editor-in-Chief of one of the top two eye research journals (Exp. Eye Res.), as well as serving as a peer reviewer for >4 dozen journals. I teach actively in the Biomedical Sciences Graduate Program of my university, both on scientific topics (Cell Biology and Biochemistry) as well as Responsible Conduct in Research. I’ve mentored numerous undergraduate, graduate, and medical students, as well as postdocs and Ophthalmology Residents in my lab (currently: 2 postdocs, 1 medical student, 1 undergrad). I also actively mentor all junior faculty in my own department (including 2 at my VA site), as well as 22 in other departments within the UB Jacobs School of Medicine and Biomedical Sciences, to assist them in their career development. In addition, I’ve been an active participant in the ARVO Global Mentoring Program, and serve on the ASCB International Affairs Committee. Overall, my research, teaching, and service activities meet or exceed the academic standards of my university and also are fully consistent with the VA HSR&D’s mission and the CRADO’s cross-cutting clinical priorities.

Eye injuries leading to compromised or lost vision are among the signature injuries sustained by our Veterans and deployed soldiers engaged in the recent conflicts in Iraq and Afghanistan (OEF, OIF). Currently, about 170,000 Veterans are legally blind, and nearly 1.5 million have some kind of visual deficit that is battle-related. Traumatic brain injury (TBI) is another signature injury of those conflicts; a significant percentage of TBI patients suffer visual deficits, nearly a third of which are blast-induced. Our goal is to understand the molecular and cellular mechanisms underlying such vision loss, and to find practical pharmacological interventions to prevent or retard the progression of those visual deficits. In addition, we’re investigating a form of Retinitis Pigmentosa (RP), about which very little is known, initially in an effort to understand the causes of the associated retinal degeneration at the molecular level and eventually to develop gene therapy approaches to ameliorate or prevent that degeneration and vision loss.