Berislav Zlokovic, MD, PhD is the director of the Zilkha Neurogenetic Institute and Professor and Chair of the Department of Physiology & Neuroscience at the Keck School of Medicine of USC, and a Professor of Biological Sciences at the Dornsife College of Letters, Arts and Sciences. Zlokovic studies the role of cerebral blood vessels in the pathogenesis and treatment of Alzheimer’s disease (AD), related disorders and stroke. Using animal models and studying human brain, his laboratory has shown that dysfunction in the blood-brain barrier (BBB) and brain microcirculation can accumulate before neuronal dysfunction in both synapses and nerve cells contributing to neurodegeneration, cognitive impairment and AD pathology. His group has identified molecular mechanisms at the BBB that maintain brain clearance of Alzheimer’s toxin amyloid-beta into the circulation, and its influx or re-entry from blood to brain, reflecting an important physiological function of the BBB in maintaining brain amyloid-beta homeostasis. These findings contributed to development of Phase 2/3 clinical trials for AD patients. He co-discovered with J.H. Griffin vasculoprotective, neuroprotective, and anti-inflammatory activities of activated protein C (APC), including the receptor requirements and downstream signaling pathways. These findings have been translated successfully into Phase 2 clinical trial of 3K3A-APC, a 2nd generation cytoprotective-selective APC analog, in ischemic stroke patients, which led to a Phase 3 pivotal trial of 3K3A-APC in patients with ischemic stroke.

Current research interests

  • We study humans at genetic risk for AD, and use transgenic models, and iPSC-based human models of the BBB and brain on a chip to understand how genes that carry risk for sporadic AD (e.g., APOE4, PICALM) affect the cerebrovascular system contributing to dementia, and AD disease onset and progression.
  • We are developing cell and gene therapy approaches for AD using i) iPSC-derived human pericytes that express different protective target genes, and/or ii) BBB cell-specific gene delivery to influence neuronal and synaptic functions.
  • We study APC biologics and mimetic peptides for 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.
  • Recently, we have initiated studies to understand how gut microbiome influences BBB in relation to neuronal and synaptic functions using transgenic and human iPSC models.
  • We initiated a program on BBB molecular signatures (snRNAseq, proteome) in health and disease using transgenic and human models, and human tissue studies.

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 17 consecutive years (2002-2019) for ranking in 1 % of the most-cited authors in the field of neurosciences and behavioral sciences. He received MetLife Award for Medical Research for “significant contributions to our understanding of Alzheimer’s disease and for bringing us closer to a cure”, Potamkin Prize from the American Academy of Neurology ” in recognition of outstanding achievements in research on Alzheimer’s and related neurodegenerative diseases”, Javits Award from NINDS “in recognition of distinguished record of substantial contributions in a field of neurological sciences”, and MERIT Award from NIA “in recognition of sustained contribution to aging and leadership and commitment to the field”. He is a fellow of the AAAS, The European Academy of Sciences, and The Dana Alliance for Brain Initiative. In 2017, 2018 and 2019, he was asked by the Nobel Assembly at Karolinska Institutet, The Nobel Committee to nominate one or more candidates for the Nobel Prize in Physiology and Medicine. He is also an active entrepreneur and inventor. He co-founded ZZ Biotech, a biotechnology company that is developing treatments for stroke and neurological disorders.