Berislav V Zlokovic, MD, PhD
|Title(s)||Chair and University Professor of Physiology & Neuroscience|
|School||Keck School of Medicine of Usc|
|Address||ZNI 101 1501 San Pablo Street|
Health Sciences Campus
Los Angeles CA 90033
|Phone||+1 323 442 2722|
|Title(s)||Mary Hayley and Selim Zilkha Chair in Alzheimer's Disease Research|
|Title(s)||Director, Zilkha Neurogenetic Institute|
Berislav Zlokovic, MD, PhD is the University Professor, Mary Hayley and Selim K. Zilkha Chair in Alzheimer’s Disease Research, director of the Zilkha Neurogenetic Institute and Professor and Chair of the Department of Physiology & Neuroscience at the Keck School of Medicine of USC. Zlokovic studies the role of brain microcirculation, particularly the blood-brain barrier (BBB) in health and disease in the adult and aging brain. He made major contributions to our understanding of the role of BBB in the pathogenesis and treatment of Alzheimer’s disease (AD) and stroke. Using animal models and studying human brain, his laboratory has shown that dysfunction in the BBB and brain microcirculation can accumulate before neuronal loss and is an early biomarker of human cognitive dysfunction. His group showed that disrupted cross-talk between BBB-associated pericytes and brain capillary endothelial cells within the neurovascular unit leads to neuronal dysfunction in both synapses and neurons. He showed that targeting the BBB cellular and molecular pathways by gene and cell therapy approaches, small molecules and/or biologics can slow down, arrest and/or prevent development of neurodegenerative changes. He has identified genes and receptors at the BBB that regulate brain levels of Alzheimer’s amyloid-beta toxin, which accumulates with aging and in AD. His team has developed new imaging techniques for studying BBB function in animal models and the living human brain. His findings contributed to development of Phase 2/3 clinical trials for AD. He co-discovered with J.H. Griffin vasculoprotective, neuroprotective, and anti-inflammatory activities of activated protein C (APC) in the CNS, including the receptor requirements and downstream signaling pathways. These findings have been translated in successfully completed Ph 1 and Ph 2 trial of 3K3A-APC, a 2nd generation cell-signaling APC analog, in ischemic stroke patients, which led to a Ph 3 efficacy pivotal trial of 3K3A-APC in patients with ischemic stroke.
Current research interests:
• We study humans at genetic risk for AD, use transgenic models, and iPSC-based human models of the BBB to understand how genes that carry risk for sporadic AD (APOE4, PICALM) affect the cerebrovascular system contributing to dementia, and AD onset and progression.
• We are developing gene and cell therapy approaches for AD using i) BBB cell-specific gene delivery; and ii) iPSC-derived human pericytes to influence and protect neuronal and synaptic functions.
• We study APC biologics and mimetic peptides in the white matter stroke, AD and ALS.
• We work on identifying small molecules that influence genes/pathways linked to AD.
• We work on CSF and imaging BBB biomarkers of human cognitive dysfunction.
• We initiated program on BBB molecular signatures (snRNAseq, proteome) in health and disease using transgenic and human models, and human brain tissue.
• Recently, we have initiated studies to understand how gut microbiome influences BBB in relation to neuronal and synaptic functions using transgenic models of AD.
Zlokovic is recognized internationally as a leader in the fields of AD and stroke research. Thomson Reuters and Clarivate Analytics listed Zlokovic as one of “The World’s Most Influential Scientific Minds” for 21 consecutive years (2002-2022) for ranking in 1 % of the most-cited authors in the field of neurosciences and behavioral sciences. He received the MetLife Award for Medical Research for “significant contributions to our understanding of Alzheimer’s disease and for bringing us closer to a cure”, the Potamkin Prize from the American Academy of Neurology in recognition of “outstanding achievements in research on Alzheimer’s and related neurodegenerative diseases”, the Javits Award from the NINDS in recognition of “distinguished record of substantial contributions in a field of neurological sciences”, the MERIT Award from the NIA in recognition of “sustained contribution to aging and leadership and commitment to the field”, and the USC Associates Award for Creativity in Research and Scholarship “the highest honor the university faculty bestows on its members for distinguished intellectual achievements”. He is the University Professor “awarded very selectively by the President based on multi-disciplinary interests and significant accomplishments in several disciplines”. He is fellow of the AAAS, The European Academy of Sciences, and The Dana Alliance for Brain Initiative. He was appointed nominator for the Nobel Prize in Physiology and Medicine for 5 consecutive years (2017-2022). He is an active entrepreneur and inventor. He co-founded ZZ Biotech, a biotechnology company that is developing treatments for stroke and neurological disorders.
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