Bruce Berkowitz, PhD
Bruce Berkowitz, PhD received undergraduate degrees in Chemistry and Philosophy from the University of Rochester, and a Ph.D. in Chemistry from Washington University. He held postdoctoral positions in NIH before taking a faculty position in the Department of Ophthalmology / University of Texas Southwestern Medical Center in Dallas. In 1996, he moved to Wayne State University School of Medicine where he is currently a Professor of Anatomy and Cell Biology, and Ophthalmology, and Director of the small animal MRI facility. He is on the editorial board of IOVS, a special issue editor for NMR in Biomedicine on “MRI of Retinal and Optic Nerve Physiology”, and part of the inaugural class of ARVO Fellows in 2009. Dr. Berkowitz research has been continuously funded since 1992 and has over 130 publications (peer-reviewed papers + book chapters).
Current imaging methods cannot measure in vivo rod cell oxidative stress, a major factor considered pathogenic in currently untreatable retinitis pigmentosa (RP) and other blinding diseases, such as diabetic retinopathy (DR). We directly measure photoreceptor oxidative stress burden in incipient RP and DR in vivo, based on the combined evaluation of rod free radical production together with their essential functions of light detection, regulated transmission of information, and visual pigment regeneration. Our new ability enables earlier evaluation of disease progression and anti-oxidant treatment efficacy than is currently possible with conventional methods. Most of our new assays of photoreceptor free radical production and function are based on endogenous contrast mechanisms which will greatly facilitate their translation into patients.
There is an urgent need for disease-modifying treatment of Alzheimer’s disease (AD) starting at its very onset. Often, spatial disorientation is observed during prodromal AD, and its occurrence predicts later dementia. Spatial confusion is linked with select hippocampal (HC) CA1 subfields that encode spatial information. HC oxidative stress is also identified at the very start of AD, and in experimental models of AD.
Our working hypothesis is that oxidative stress in select CA1 subregions in vivo causes deterioration of spatial memory. This hypothesis cannot currently be tested longitudinally and translationally using conventional methods. We have pioneered QUEnch-assiSTed MRI (QUEST MRI) is a sensitive new tool that has been validated against “gold standard” methods. The QUEST MRI index of abnormally high production of paramagnetic free radicals in specific brain regions is a greater-than-normal spin-lattice relaxation rate R1 (1/T1) that can be returned to baseline after acute antioxidant administration. Our QUEST MRI studies have confirmed dorsal HC CA1-specific oxidative stress in spontaneous and familial AD mouse models with declines in spatial learning and memory in conjunction with HC CA1 oxidative stress measured ex vivo. We also find downstream consequences of oxidative stress such as greater-than-normal amounts of the lipid peroxidation product 4-hydroxynonenal (HNE), dorsal HC CA1 calcium dysregulation and reductions in dorsal HC CA1 calcium-dependent afterhyperpolarization (AHP).
Our goal is to use QUEST MRI for testing in vivo antioxidant therapeutic strategies to mitigate a clinically important early decline in spatial memory preceding later loss of personhood in AD.