David Antonetti, Ph.D.
Dr. Antonetti received his PhD in Cellular and Molecular Biology at The Penn State College of Medicine under the direction of Dr. Leonard Jim Jefferson and was a post-doctoral fellow in Cellular and Molecular Physiology at the Joslin Diabetes Center at Harvard Medical School under the direction of Dr. C. Ronald Kahn. Upon returning to Penn State, he was one of the first to bring high-level signal transduction expertise to the problem of diabetic retinopathy and the blood-retinal barrier. Over the last 20 years, he has become one of the world’s leading experts in mechanisms of vascular permeability in diabetic retinopathy, the role of the blood retinal barrier in normal physiology, and the molecular mechanisms that underlie angiogenesis and neovascularization. These efforts have allowed him to develop new experimental treatments that show promising pre-clinical results. He has received awards including the Jules Francois Prize for Young Investigator at Ophthalmologia Beligica, the Hinkle Society Mid-career Translational Research Award, and the Most Inspirational Teacher Award for graduate education at Penn State. He held the very prestigious Jules and Doris Stein Professorship from Research to Prevent Blindness for the allotted 5 years. Currently he is the inaugural Roger W. Kittendorf Research Professor of Ophthalmology and Visual Sciences. Dr. Antonetti is the Scientific Director at the Kellogg Eye Center contributing to establishing the direction and management of preclinical vision research for the Department. His work has been noted by presentations at key meetings such as the American Diabetes Association, the International Symposium of the Blood-Brain Barrier, Gordon Research Conferences, and the International Symposium on Signal Transduction at the Blood-Brain and Blood-Retina Barriers. Of particular note, his translational impact has been recognized by clinicians by his presentations at the American Uveitis Society, the American Academy of Ophthalmology, the ARVO Vision Innovation and Venture forum, and the University of Pittsburgh, Washington University, and Trinity College in Dublin.
- Ph.D., Pennsylvania State University
Our long-term goal is to contribute to the development of novel treatments to prevent or reverse the debilitating loss of vision from diabetes and stroke.
The tight junction complex contributes an essential role in multi-cellular organisms by helping to create defined environments between tissues. Tight junctions create a tight seal between cells controlling the flux of fluids, proteins and even ions across tissue barriers. These barriers provide an essential function in a variety of tissues including the intestine, lung and kidneys. Our laboratory is specifically interested in the tight junction complex in specialized regions of the vasculature that help to create the blood-brain and blood-retinal barrier. The tight junctions that connect the endothelial cells in the brain and retina are needed for normal neural function and contribute to the neurovascular unit. This vascular barrier may be compromised in a variety of disease states.
Diabetic retinopathy is the leading cause of visual loss in working age adults and is characterized by increased vascular permeability, leading to edema, or fluid accumulation, in the retina. Our laboratory works to understand the cellular and molecular basis for this change in vascular permeability by exploring the changes in the tight junction complex that controls the blood-retinal barrier. Our laboratory utilizes biochemical approaches such as mass spectrometry, cell biology techniques such as mutational analysis in vascular endothelial cell culture, and transgenic mouse studies in models of diabetic retinopathy, in order to understand the mechanisms by which diabetes alters the tight junctions in the blood-retinal barrier. Much of this research has centered on understanding how growth factors and cytokines signal to the tight junction complex and regulate vascular permeability. Our laboratory was one of the first to identify phosphorylation of junctional protein occludin as a regulator of barrier properties. Our recent studies demonstrate that a transgenic mouse models expressing point mutants preventing this phosphorylation preserves the retinal vascular barrier during diabetes and importantly, prevents vision loss. Future studies will explore the intimate relationship between the retinal blood vessels and neural function to better understand the neurovascular unit.