Berislav V. Zlokovic 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 has a life-long career in studying the role of cerebral blood vessels in the pathogenesis and treatment of neurological disorders such as Alzheimer’s disease and related disorders and stroke. Using animal models and studying human brain, his laboratory has shown that dysfunction in the blood-brain barrier and brain microcirculation can accumulate before neuronal dysfunction and contribute to the onset and progression of different neurological disorders and symptoms including dementia. His research team has identified the cellular and molecular mechanisms in cerebral blood vessels causing disruption of the blood-brain barrier and neurovascular unit, which leads to neurodegeneration in models of Alzheimer’s disease, pericyte-deficient rodents and stroke. His group has also identified molecular mechanisms at the blood-brain barrier that maintain clearance of Alzheimer’s toxin amyloid-beta from the brain into the circulation, and its influx or re-entry from the circulation into the brain, reflecting an important physiological function of the blood-brain barrier in maintaining brain amyloid-beta homeostasis. Discoveries of his research team have contributed to the development of clinical trials for Alzheimer’s disease (Phase 2 and 3 studies) based on clearance of amyloid-beta and/or blockade of its re-entry into the brain, and stroke based on activated protein C treatment that has currently completed assessment in stroke patients (Phase 2) as a neuroprotective agent.

Zlokovic’s more recent research interests are focused on genes that influence the risk for Alzheimer’s disease, particularly how APOE4, PICALM, and CLU affect the cerebrovascular system. In these studies, he uses different transgenic animal models, and human inducible pluripotent stem cell-derived neuronal and blood-brain barrier in vitro models of neurological disorders. He and his research team have also developed novel neuroimaging methods in the living human brain and animal models and novel molecular biomarkers of the neurovascular unit to evaluate how blood-brain barrier and cerebral blood flow functions influence brain connectivity and cognition. He also remains interested in developing advanced approaches with activated protein C therapy for stroke and other neurological disorders.

Zlokovic is recognized internationally as a leader in the fields of Alzheimer’s disease and stroke. Thomson Reuters listed Zlokovic as one of “The World’s Most Influential Scientific Minds” in 2002-2012, 2014 and 2016 for ranking in one percent of the most-cited authors in the field of neurosciences and behavioral sciences. He is the recipient of many awards, including 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 National Institute on Neurological Disorders and Stroke "in recognition of distinguished record of substantial contributions in a field of neurological sciences”, and the MERIT Award from the National Institute on Aging "in recognition of sustained contribution to aging and leadership and commitment to the field”. He is a fellow of the American Association for Advancement of Science (AAAS) and a member of The Dana Alliance for Brain Initiative, the Serbian Academy of Sciences and Arts and The European Academy of Sciences (Academia Europeae) - the Life Sciences Class. In 2016, 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 2017.

Zlokovic is an active entrepreneur and inventor. He co-founded ZZ Biotech, a biotechnology company that is dedicated to developing new treatments for stroke and neurological disorders.

Featured Publications:

i-10 index: 208; h-index: 82; >350 publications; >26,150 citations (Google Scholar, May 2017); complete list in Google Scholar: https://goo.gl/2Npcj2

Selected Publications representing interests of the Zlokovic laboratory.

Kisler K, Nelson A, Montagne A, Zlokovic BV (2017) Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer’s disease. Nature Reviews Neuroscience (doi: 10.1038/nrn.2017.48)

Kisler K, Nelson AR, Rege SV, Ramanathan A, Wang Y, Ahuja A, Lazic D, Tsai PS, Zhao Z, Zhou Y, Boas DA, Sakadžic S, Zlokovic BV (2017) Pericyte degeneration leads to neurovascular uncoupling and limits oxygen supply to brain. Nature Neuroscience 20, 406-416.

Wang Y, Zhao Z, Rege S, Griffin JH, Goldman SA, Zlokovic BV (2016) 3K3A-APC stimulates post-ischemic neuronal repair by human neural progenitor cells in mice. Nature Medicine 22 (9): 1050-1055.

Sweeney MD, Ayyadurai S, Zlokovic BV (2016) Pericytes of the neurovascular unit: key functions and signaling pathways. Nature Neuroscience 19 (6): 771-783.

Zhao Z, Nelson A, Betsholtz C, Zlokovic BV (2015) Establishment and dysfunction of blood-brain barrier. Cell 163, Nov 19;163(5):1064-78.

Zhao Z, Sagare AP, Ma Q, Halliday MR, Kong P, Kisler K, Winkler EA, Ramanathan A, Kanekiyo T, Bu G, Owens NQ, Rege SV, Si G, Ahuja A, Zhu D, Miller CA, Schneider JA, Maeda M, Maeda T, Sugawara T, Ichida JK, Zlokovic BV (2015) Central role for PICALM in amyloid-? blood-brain barrier transcytosis and clearance. Nature Neuroscience 18, 978-987.

Winkler EA, Nishida Y, Sagare AP, Rege SV, Bell RD, Perlmutter D, Sengillo JD, Hillman S, Kong P, Nelson AR, Sullivan JS, Zhao Z, Meiselman HJ, Wendy RB, Soto J, Abel ED, Makshanoff J, Zuniga E, De Vivo DC, Zlokovic BV (2015) GLUT1 reductions exacerbate Alzheimer’s disease vasculo-neuronal dysfunction and degeneration. Nature Neuroscience 18, 521-530.

Montagne A, Barnes SR, Sweeney MD, Halliday MR, Sagare AP, Zhao Z, Toga AW, Jacobs RE, Liu CY, Amezcua L, Harrington MG, Chui HC, Law M, Zlokovic BV (2015) Blood-brain barrier breakdown in the aging human hippocampus. Neuron 85, 296-302.

Griffin JH, Zlokovic BV, Mosnier LO (2015) Activated Protein C: Biased for Translation. Blood 125 (19), 2898-2907.

Zhao Z and Zlokovic BV (2014) Blood-Brain Barrier: A Dual Life of MFSD2A? Neuron 82, 728–730.

Winkler EA, Sengillo JD, Sagare AP, Zhao Z, Ma Q, Zuniga E, Wang Y, Zhong G, Sullivan JS, Griffin JH, Cleveland DW, Zlokovic BV (2014) Blood-spinal cord barrier disruption contributes to early motor neuron degeneration in ALS model mice. Proceedings of the National Academy of Sciences USA 111(11), E1035-42.

Bell RD, Winkler E, Sagare A, Singh I, Deane R, Wu Z, Holtzman DM, Betsholtz C, Armulik A, Sallstrom J, Berk B, Zlokovic BV (2012) Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature 485, 512-516.

Deane R, Singh I, Sagare A, Bell R, Ross NT, Larue B, Love R, Perry S, Deane RJ, Thiyagarajan M, Zarcone T, Friedman A, Miller BL, Zlokovic BV (2012) A novel multi-modal RAGE-specific inhibitor controls amyloid-beta-mediated brain disorder in mice. Journal of Clinical Investigation 122 (4), 1377-1392.

Winkler E, Bell R, Zlokovic BV (2011) Functions of CNS pericytes in health and disease. Nature Neuroscience 14, 1398-1405.

Zlokovic BV (2011) Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nature Reviews Neuroscience 12, 723-738.

Winkler EA, Bell RD, Zlokovic BV (2011) Lack of Smad and Notch Leads to a Fatal Game of Brain Pericyte Hopscotch. Developmental Cell (Cell) 20 (3), 279-281.

Zlokovic BV, Griffin JH (2011) Activated protein C cytoprotective pathways and implications for stroke and neurological disorders. Trends in Neurosciences 34 (4), 1198-2009.

Zlokovic BV (2010) Neurodegeneration and the neurovascular unit. Nature Medicine 16(12), 1370-71.

Bell RD, Winkler EA, Sagare A, Singh I, LaRue B, Deane R, Zlokovic BV (2010) Pericytes control key neurovascular functions and the neuronal phenotype in the adult brain and during brain aging. Neuron 68, 409-427.

Zhu D, Wang Y, Singh I, Bell RD, Deane R, Zhong Z, Sagare A, Winkler EA, Zlokovic BV (2010) Protein S controls hypoxic/ischemic blood-brain barrier disruption through the TAM receptor Tyro3 and sphingosine 1-phosphate receptor. Blood 115, 4963-4972.

Bell RD , Deane R, Chow N, Long X, Sagare A, Singh I, Streb JW, Guo H, Rubio A, Van Nostrand W, Miano JP, Zlokovic BV (2009) SRF and myocardin regulate LRP-mediated amyloid-beta clearance in brain vascular cells. Nature Cell Biology 11(2), 143-153.

Zhong Z, Ilieva H, Hallagan L, Bell R, Singh I, Paquette N, Thiyagarajan M, Deane R, Fernandez JA, Lane S, Zlokovic AB, Liu T, Griffin JH, Chow N, Castellino F, Stojanovic K, Cleveland DW, Zlokovic BV (2009) Activated protein C slows ALS-like disease by transcrptionally inhibiting SOD1 in motor neurons and microglial cells. Journal of Clinical Investigation 119(11), 3437-3440.

Deane R, Sagare A, Hamm K, Parisi M, Lane S, Finn MB, Holtzman DM, Zlokovic BV (2008) Apolipoprotein E isoform-specific disruption of Alzheimer’s amyloid ?-peptide clearance from mouse brain Journal of Clinical Investigation 118(12), 4002-4013.

Zhong Z, Deane R, Zarina A, Parisi M, Shapovalov Y, 0’Banion K, Stojanovic K, Sagare A, Boillee S, Cleveland DW, Zlokovic BV (2008) ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration. Nature Neuroscience 11(4), 420-422.

Zlokovic BV (2008) Blood-brain barrier in health and chronic neurodegenerative disorders. Neuron, 57, 178-201.

Sagare A, Deane R, Bell RD, Johnson B, Hamm K, Pendu R, Marky A, Lenting PJ, Wu Z, Zarcone T, Goate A, Mayo K, Pelmutter D, Coma M, Zhong Z, Zlokovic BV (2007) Clearance of amyloid-beta by circulating lipoprotein receptors. Nature Medicine 13 (9), 1029-1031.

Chow N, Bell RD, Deane R, Streb JW, Chen J, Brooks A, Van Nostrand W, Miano JM, Zlokovic BV (2007). Serum response factor and myocardin mediate cerebral arterial hypercontractility and blood flow dysregulation in Alzheimer’s phenotype. Proceedings of the National Academy of Sciences USA 104, 823-828.

Mosnier L, Zlokovic BV, Griffin JH (2007) The cellular protein C pathway. Blood 109(8), 161-172.

Cheng T, Petraglia A, Li Z, Meedakshisudaram T, Wu Z, Zhong Z, Liu D, Maggirwar SB, Deane R, Fernandez J, LaRue B, Griffin J, Chopp M, Zlokovic BV (2006) Activated protein C inhibits tissue plasminogen activator-induced brain hemorrhage. Nature Medicine 12 (11), 1278-1285.

Zlokovic BV (2006) Remodeling after stroke. Nature Medicine 12 (4) 390-391.

Wu Z, Guo H, Chow N, Sallstrom J, Bell RD, Deane R, Brooks A, Kanagala S, Rubio A, Sagare A, Liu D, Li F, Armstrong D, Gasiewicz T, Zidovetski R, Song H, Hofman F, Zlokovic BV (2005) Role of MEOX2 homeobox gene in neurovascular dysfunction in Alzheimer disease. Nature Medicine 11(9), 959-965.

Zlokovic BV (2005) Neurovascular mechanisms of Alzheimer’s neurodegeneration. Trends in Neurosciences 28, 202-208.

Deane R, Wu Z, Davis J, Yan SD, Hamm K, Sagare A, Xu F, Spijkers P, Lenting PJ, Van Nostrand WE, Zlokovic BV (2004) LRP-amyloid-beta interaction mediates differential brain efflux of Abeta isoforms Neuron 43, 33-44.

Liu D, Cheng T, Guo H, Fernandez AJ, Griffin JH, Song X, Zlokovic BV (2004) Tissue plasminogen activator neurovascular toxicity is controlled by activated protein C. Nature Medicine 10, (12), 1379-1383.

Guo H, Liu D, Gelbard H, Cheng T, Fernandez JA, Insalaca R, Griffin JH, Zlokovic BV (2004) Activated protein C prevents neuronal apoptosis via protease activated receptors 1 and 3. Neuron 41, 563-572.

Deane R, Yan SD, Kumar R, Jovanovic S, LaRue B, Welch D, Maness L, Yu J, Zhu H, Ghiso J, Frangione B, Schmidt AM, Arnold B, Liliensiek B, Nawroth P, Hofman F, Kindy M, Stern D, Zlokovic BV (2003) RAGE mediates amyloid-ß peptide transport across the blood-brain barrier and accumulation in brain. Nature Medicine 9(7), 907-913.

Cheng T, Liu D, Fernández JA, Griffin JH, Castellino F, Rosen E, Fukudome K, Zlokovic BV (2003) Activated protein C blocks P53-mediated apoptosis in ischemic human brain endothelium and is neuroportective. Nature Medicine 9, 338-342.

Domotor E, Benzakour O, Griffin JH, Yule D, Fukudome K, Zlokovic BV (2003) Activated protein C alters cytosolic Ca2+ flux in human brain endothelium via binding to endothelial protein C receptor and activation of protease-activated receptor-1. Blood 101, 4797-4801.

Shibata M, Subramanyan RK, Amar A, Fernandez J, Griffin J, Zlokovic BV (2001) Anti-inflammatory, antithrombotic and neuroprotective effects of activated protein C in a murine model of focal ischemic stroke with cerebrovascular thrombosis. Circulation 103, 1799-1805.

Shibata M, Yamada S, Kumar RS, Calero M, Bading B, Frangione B, Holtzman DM, Miller CA, Strickland DK, Ghiso J, Zlokovic BV (2000) Clearance of Alzheimer’s amyloid-ß1-40 peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. Journal of Clinical Investigation 106(12), 1489-1499.

Zlokovic BV, Shinya Y, Holtzman D, Ghiso J, Frangione B (2000) Clearance of amyloid ß-peptide from brain: transport or metabolism? Nature Medicine 6, 718-719.

Mackic JB, Stins M, McComb JG, Calero M, Ghiso J, Kim KS, Yan SD, Stern D, Schmidt AM, Frangione B, Zlokovic BV (1998) Human blood-brain barrier receptors for Alzheimer's amyloid-? 1-40: Asymmetrical binding, endocytosis and transcytosis at the apical side of brain microvascular endothelial cell monolayer. Journal of Clinical Investigation 102, 734-743.

Zlokovic BV, Martel CL, Matsubara E, McComb JG, Zheng G, McCluskey RT, Frangione B, Ghiso J (1996) Glycoprotein 330/megalin: Porbable role in receptor-mediated transport of apolipoprotein J alone and in a complex with Alzheimer's Disease amyloid-? at the blood-brain and blood-cerebrospinal fluid barriers. Proceedings of the National Academy of Sciences USA 93, 4229-4236.