Patricia R. Spilman, M.A.

Drug Discovery Laboratory, Department of Neurology, David Geffen School of Medicine at UCLA

Drug Discovery Laboratory
710 Westwood Plaza, Reed Building - Room 3256
Los Angeles, CA 90095-1769
Tel: (310) 794-4787
Fax: (310) 825-6956
Email: pspilman@mednet.ucla.edu

Biography

I have over 20 years of experience in neurodegenerative disease research, including 12 years with world-renowned neuropathologist Stephen J. DeArmond, M.D., Ph.D., and Nobel Laureate, Stanley Prusiner, M.D. at the University of California, San Francisco. For the last ten years, my focus has been on development of new therapeutics as part of an Alzheimer’s disease (AD) drug discovery team following a pharmaceutical industry model in an academic research setting. Our work has resulted in elevation of AD therapeutic candidate tropisetron to clinical trials. I currently supervise and perform in vivo pharmacokinetic/dynamic studies, collect and analyze all project data, and am frequently the presenter of project status to funding partners. The success of our current program, starting at the Buck Institute for Research on Aging in Novato, CA and continuing at the Mary S. Easton Center for AD Research at UCLA, has resulted in generation of multiple NCEs and garnered significant venture capital investment. In addition to writing grants and three first-author publications in the last 6 years, I give presentations at international scientific conferences such as the Alzheimer’s Association International Conference and the Society for Neuroscience Conference, and to the lay public.

Affiliations

Drug Discovery Laboratory (DDL)

Education and Degrees

B.A. Physiology and Anatomy, University of California, Berkeley

M.S. Physiology and Behavioral Biology, California State University, San Francisco

Publications

DeArmond SJ, Qiu Y, Sanchez H, Spilman P, Ninchak-Casey A, Alonso D, Daggett V. PrPC glycoform heterogeneity as a function of brain region: implications for selective targeting of neurons by prion strains. J Neuropathol Exp Neurol 1999 Sep 58(9):1000-1009.

Bouzamondo-Bernstein E, Hopkins SD, Spilman P, Uyehara-Lock J, Deering C, Safar J, Prusiner SB, Ralston HJ, DeArmond SJ. The neurodegenerative sequence in prion disease: evidence from functional, morphological, and ultrastructural studies of GABAergic systems. Neurol J Neuropathol Exp 2004 Aug 63(8):882-899.

Galvan V, Banwait S, Spilman P, Gorostiza OF, Peel A, Ataie M, Crippen D, Huang W, Sidhu G, Ichijo H, Bredesen DE. Interaction of ASK1 and the beta-amyloid precursor protein in a stress - signaling complex. Neurobiol Dis 2007 Oct; 28(1):65-75.

Spilman P, Lessard P, Sattavat M, Bush C, Tousseyn T, Huang EJ, Giles K, Golde T, Das P, Fauq A, Prusiner SB, DeArmond SJ. A gamma-secretase inhibitor and quinacrine reduce prions and prevent dendritic degeneration in murine brains. PNAS (USA) 2008 Jul 29;105(30):10595-10600. PMID: 18647832; PMCID: PMC2492499

Butterfield DA, Galvan V, Lange MB, Tang H, Sowell RA, Spilman P, Fombonne J, Gorostiza O, Zhang J, Sultana R, Bredesen DE. In vivo oxidative stress in brain of Alzheimer’s disease transgenic mice: requirements for methionine 35 in amyloid beta peptide of APP. Free Radic Biol Med 2010 Jan 1:48(1):136-144. PMID: 19854267; PMCID: PMC2818480

Spilman P, Podlutskaya N, Hart MJ, Debnath J, Gorostiza O, Galvan V. Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease. PLoS One 2010 Apr 1:5(4):e9979. PMID: 20376313; PMCID: PMC2848616

Zhang J, Rao RV, Spilman P, Mangada J, Xie L, Vitelli C, Gorostiza OF, Madden DT, Zeng X, Jin K, Hart MJ, Bredesen DE, Galvan V. Endogenously EGFP-labeled mouse embryonic stem cells. Aging Dis 2011 Feb;2:18. PMID: 21874159; PMCID: PMC3160738

Zhang J, Spilman P, Chen S, Gorostiza O, Matalis A, Niazi K, Bredesen DE, Rao RV. The small co- chaperone p23 overexpressing transgenic mouse. J Neurosci Methods 2013 Jan 30;212(2):190-194. PMID: 23022695; PMCID: PMC3562756

Frankowski H, Alavez S, Spilman P, Mark K, Nelson J, Mollahan P, Rao R, Chen S, Lithgow G, Ellerby M. Dimethyl sulfoxide and dimethyl formamide increase lifespan of C. elegans in liquid.Mech. Ageing Develop 2013 Mar;134(3-4):69-78. PMID: 23313473

Descamps O, *Spilman P, Zhang Q, Libeu CP, Poksay K, Gorostiza O, Campagna J, Jagodzinska B, Bredesen DE, John V. AβPP-Selective BACE Inhibitors (ASBI): Novel Class of Therapeutic Agents for Alzheimer’s Disease. J Alz Dis 2013;37(2):343-55. *Co-wrote manuscript. PMID: 23948888; PMCID: PMC3971881

Zhang Q, Descamps O, Hart MJ, Poksay KS, Spilman P, Kane DJ, Gorostiza O, John V, Bredesen DE. Paradoxical effect of TrkA inhibition in Alzheimer's disease models. J Alzheimers Dis 2014;40(3):605-617. PMID: 24531152; PMCID: PMC4091737

Spilman P, Descamps O, Gorostiza O, Peters-Libeu C, Poksay KS, Matalis A, Campagna J, Patent A, Rao R, John V, Bredesen DE. The multi-functional drug tropisetron binds APP and normalizes cognition in a murine Alzheimer's model. Brain Res 2014 Mar 10;1551:25-44. Issue Cover. doi:10.1016/j.brainres.2013.12.029. PMID: 24389031; PMCID: PMC4001856 [Available on 2015/3/10]

Alam MP, Jagodzinska B, Campagna J, Spilman P, John V. C-O bond formation in a microfluidic reactor: high yield SNAr substitution of heteroaryl chlorides. Tetrahedron Letter 2016;57(19):2059-2062. doi:10.1016/j.tetlet.2016.03.095