Joseph M Castellano, PhD
- ASSISTANT PROFESSOR (PENDING) | Neuroscience
Research Topics:Aging, Alzheimer's Disease, Blood-Brain Barrier, Epigenetics, Extracellular Matrix, Hippocampus, Immunology, Memory, Microglia, Neuro-degeneration/protection, Neuroscience, Synaptic Plasticity, Transgenic Mice
As a graduate student, I studied how the strongest genetic risk factor for Alzheimer's disease influences metabolism of the pathogenic peptide amyloid beta from brain interstitial fluid. In David Holtzman’s group, I used in vivo microdialysis to show in behaving mice that clearance of this peptide is impeded by the presence of APOE4, whereas clearance in the context of more inert or protective forms is faster. As I transititoned into my postdoctoral training, I was fascinated by the possibility that brain function may be, in part, shaped by our immune system and by unexplored activities present within our circulation. In my postdoctoral work with Tony Wyss-Coray, I sought to identify and characterize factors in the periphery that reverse features of brain aging, finding that systemic treatment with umbilical cord plasma revitalizes hippocampal function in aged mice. My laboratory now focuses on characterizing proteins, including TIMP2, and their action in mediating long-range effects on circuits in the brain in the context of Alzheimer's disease and other disorders.
Fellowship, Stanford University
PhD, Washington University in St. Louis
Castellano JM, Mosher KI, Abbey RJ, McBride AA, James ML, Berdnik D, Shen JC, Zou B, Xie XS, Tingle M, Hinkson IV, Angst MS, Wyss-Coray T. Human umbilical cord plasma proteins revitalize hippocampal function in aged mice. Nature 2017 Apr; 544(7651).
Czirr E, Castello NA, Mosher KI, Castellano JM, Hinkson IV, Lucin KM, Baeza-Raja B, Ryu JK, Li L, Farina SN, Belichenko NP, Longo FM, Akassoglou K, Britschgi M, Cirrito JR, Wyss-Coray T. Microglial complement receptor 3 regulates brain Aβ levels through secreted proteolytic activity. The Journal of experimental medicine 2017 Apr; 214(4).
Castellano JM, Palner M, Li SB, Freeman GM, Nguyen A, Shen B, Stan T, Mosher KI, Chin FT, de Lecea L, Luo J, Wyss-Coray T. In vivo assessment of behavioral recovery and circulatory exchange in the peritoneal parabiosis model. Scientific reports 2016 Jul; 6.
Zhang XD, Wang H, Antaris AL, Li L, Diao S, Ma R, Nguyen A, Hong G, Ma Z, Wang J, Zhu S, Castellano JM, Wyss-Coray T, Liang Y, Luo J, Dai H. Traumatic Brain Injury Imaging in the Second Near-Infrared Window with a Molecular Fluorophore. Advanced materials (Deerfield Beach, Fla.) 2016 Aug; 28(32).
Castellano JM, Kirby ED, Wyss-Coray T. Blood-Borne Revitalization of the Aged Brain. JAMA neurology 2015 Oct; 72(10).
Shieh P, Dien VT, Beahm BJ, Castellano JM, Wyss-Coray T, Bertozzi CR. CalFluors: A Universal Motif for Fluorogenic Azide Probes across the Visible Spectrum. Journal of the American Chemical Society 2015 Jun; 137(22).
Villeda SA, Plambeck KE, Middeldorp J, Castellano JM, Mosher KI, Luo J, Smith LK, Bieri G, Lin K, Berdnik D, Wabl R, Udeochu J, Wheatley EG, Zou B, Simmons DA, Xie XS, Longo FM, Wyss-Coray T. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nature medicine 2014 Jun; 20(6).
Baruch K, Deczkowska A, David E, Castellano JM, Miller O, Kertser A, Berkutzki T, Barnett-Itzhaki Z, Bezalel D, Wyss-Coray T, Amit I, Schwartz M. Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function. Science (New York, N.Y.) 2014 Oct; 346(6205).
Luo J, Nguyen A, Villeda S, Zhang H, Ding Z, Lindsey D, Bieri G, Castellano JM, Beaupre GS, Wyss-Coray T. Long-term cognitive impairments and pathological alterations in a mouse model of repetitive mild traumatic brain injury. Frontiers in neurology 2014; 5.
Mak AC, Pullinger CR, Tang LF, Wong JS, Deo RC, Schwarz JM, Gugliucci A, Movsesyan I, Ishida BY, Chu C, Poon A, Kim P, Stock EO, Schaefer EJ, Asztalos BF, Castellano JM, Wyss-Coray T, Duncan JL, Miller BL, Kane JP, Kwok PY, Malloy MJ. Effects of the absence of apolipoprotein e on lipoproteins, neurocognitive function, and retinal function. JAMA neurology 2014 Oct; 71(10).
Verghese PB, Castellano JM, Garai K, Wang Y, Jiang H, Shah A, Bu G, Frieden C, Holtzman DM. ApoE influences amyloid-β (Aβ) clearance despite minimal apoE/Aβ association in physiological conditions. Proceedings of the National Academy of Sciences of the United States of America 2013 May; 110(19).
Ulrich JD, Burchett JM, Restivo JL, Schuler DR, Verghese PB, Mahan TE, Landreth GE, Castellano JM, Jiang H, Cirrito JR, Holtzman DM. In vivo measurement of apolipoprotein E from the brain interstitial fluid using microdialysis. Molecular neurodegeneration 2013 Apr; 8.
Castellano JM, Deane R, Gottesdiener AJ, Verghese PB, Stewart FR, West T, Paoletti AC, Kasper TR, DeMattos RB, Zlokovic BV, Holtzman DM. Low-density lipoprotein receptor overexpression enhances the rate of brain-to-blood Aβ clearance in a mouse model of β-amyloidosis. Proceedings of the National Academy of Sciences of the United States of America 2012 Sep; 109(38).
Castellano JM, Kim J, Stewart FR, Jiang H, DeMattos RB, Patterson BW, Fagan AM, Morris JC, Mawuenyega KG, Cruchaga C, Goate AM, Bales KR, Paul SM, Bateman RJ, Holtzman DM. Human apoE isoforms differentially regulate brain amyloid-β peptide clearance. Science translational medicine 2011 Jun; 3(89).
Verghese PB, Castellano JM, Holtzman DM. Apolipoprotein E in Alzheimer's disease and other neurological disorders. The Lancet. Neurology 2011 Mar; 10(3).
Kim J, Castellano JM, Jiang H, Basak JM, Parsadanian M, Pham V, Mason SM, Paul SM, Holtzman DM. Overexpression of low-density lipoprotein receptor in the brain markedly inhibits amyloid deposition and increases extracellular A beta clearance. Neuron 2009 Dec; 64(5).