Paul H. Patterson, the Anne P. and Benjamin F. Biaggini Professor of Biological Sciences, Emeritus, at Caltech, and a neuroscientist and developmental biologist who created novel behavioral models of schizophrenia and autism in mice, died on June 25, 2014. He was 70 years old.
Paul H. Patterson's early career was very much a product of one the first golden ages of modern neuroscience. Having completed his Ph.D. with William Lennarz at Johns Hopkins in 1970 (working on prokaryotic membrane biology), Paul fatefully decided to head to Harvard Medical School as a postdoctoral fellow, eventually becoming a faculty member, in the first Department of Neurobiology established in the U.S. In this unique environment, Paul pioneered the primary culture of peripheral neurons and used this system to discover that developing sympathetic neurons could switch their neurotransmitter phenotype from noradrenergic to cholinergic, in response to environmental factors. This was a fundamental discovery in Neuroscience, as it violated the "one neuron, one transmitter" concept, and demonstrated that neurotransmitter identity is not genetically determined and immutable. Paul's quest to purify and molecularly characterize the factor that controls this switch culminated in 1989, five years after his move to Caltech, with the purification and microsequencing of the "cholinergic differentiation factor." The sequence of this factor revealed, astonishingly, that it was identical to Leukemia Inhibitory Factor ("LIF"), a cytokine previously identified based on its immunological function. This discovery, along with his early adoption of monoclonal antibodies as a tool to query the nervous system, marked the beginning of Paul's transformation into a "neuroimmunologist."
Paul continued his work on the effects of cytokines on the developing and diseased nervous system, deploying antibodies both as tools and therapeutic candidates. In the early 2000's, these lines of research led Paul to become increasingly interested in the interplay between the biology of inflammation and its impact on the developing brain and behavior. Emboldened by his unique perspective, Paul expanded on the link between the immune system and behavior by establishing a mouse model of autism and schizophrenia based on studies showing infection during pregnancy increased disease risk. He showed that stimulation of the immune system in pregnant animals results in offspring with altered behaviors, and characterized the immune pathways that promoted these outcomes. This discovery served to increase awareness for environmental influences on neurodevelopmental conditions. In one of his most recent studies, Paul demonstrated that the gut microbiome, the diverse collection of intestinal bacteria, regulates behaviors in a mouse model of autism, and that probiotic treatment leads to improvements in behavioral deficits. These studies provide the hope that perhaps neurodevelopmental disorders with strong environmental influences may be ameliorated with microbial therapies. Paul's groundbreaking discoveries have advanced novel paradigms in Neuroscience and Immunology, and introduced concepts that will continue to be developed by researchers worldwide, including many of his trainees.
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Bauman, M.D., Iosif, A.M., Smith, S.E., Bregere, C., Amaral, D.G., Patterson, P.H. (2013) Activation of the maternal immune system during pregnancy alters behavioral development of Rhesus monkey offspring. Bio. Psychiatry Sep 4. pii: S0006-3223(13)00673-2. doi: 10.1016/j.biopsych.2013.06.025. [Epub ahead of print]
Garay, Paula A. and Hsiao, Elaine Y. and Patterson, Paul H. and McAllister, A. K. (2013) Maternal immune activation causes age- and region-specific changes in brain cytokines in offspring throughout development. Brain, Behavior, and Immunity, 31 . pp. 54-68. ISSN 1090-2139. Download
Khoshnan, Ali and Ou, Susan and Ko, Jan and Patterson, Paul H. (2013) Antibodies and intrabodies against Huntingtin: Production and screening of monoclonals and single-chain recombinant forms. In: Trinucleotide Repeat Protocols. Methods in Molecular Biology. No.1010. Springer , New York, pp. 231-251. ISBN 9781627034104 Download
McAllister, A. Kimberley and Patterson, Paul H. (2012) Introduction to special issue on neuroimmunology in brain development and disease. Developmental Neurobiology, 72 (10). pp. 1269-1271. ISSN 1932-8451. Download
Hsiao, Elaine Y. and Patterson, Paul H. (2012) Placental regulation of maternal-fetal interactions and brain development. Developmental Neurobiology, 72 (10). pp. 1317-1326. ISSN 1932-8451. Download
Bugg, Charles W. and Isas, J. Mario and Fischer, Torsten and Patterson, Paul H. and Langen, Ralf (2012) Structural features and domain organization of Huntingtin fibrils. Journal of Biological Chemistry, 287 (38). pp. 31739-31746. ISSN 0021-9258. Download
Hsiao, Elaine Y. and McBride, Sara W. and Chow, Janet and Mazmanian, Sarkis K. and Patterson, Paul H. (2012) Modeling an autism risk factor in mice leads to permanent immune dysregulation. Proceedings of the National Academy of Sciences of the United States of America, 109 (31). pp. 12776-12781. ISSN 0027-8424. Download
Khoshnan, Ali and Patterson, Paul H. (2012) Elevated IKKα accelerates the differentiation of human neuronal progenitor cells and induces MeCP2-dependent BDNF expression. PLoS ONE, 7 (7). e41794. ISSN 1932-6203. Download
Malkova, Natalia V. and Yu, Collin Z. and Hsiao, Elaine Y. and Moore, Marlyn J. and Patterson, Paul H. (2012) Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism. Brain, Behavior and Immunity, 26 (4). pp. 607-616. ISSN 0889-1591 . Download
Garbett, K. A. and Hsiao, E. Y. and Kálmán, S. and Patterson, P. H. and Mirnics, K. (2012) Effects of maternal immune activation on gene expression patterns in the fetal brain. Translational Psychiatry, 2 . Art. No. e98. ISSN 2158-3188 . Download
Deverman, Benjamin E. and Patterson, Paul H. (2012) Exogenous leukemia inhibitory factor stimulates oligodendrocyte progenitor cell proliferation and enhances hippocampal remyelination. Journal of Neuroscience, 32 (6). pp. 2100-2109. ISSN 0270-6474. Download
Carlisle, Holly J. and Luong, Tinh N. and Medina-Merino, Andrew and Schenker, Leslie and Khorosheva, Eugenia and Indersmitten, Tim and Gunapala, Keith M. and Steele, Andrew D. and O'Dell, Thomas J. and Patterson, Paul H. and Kennedy, Mary B. (2011) Deletion of densin-180 results in abnormal behaviors associated with mental illness and reduces mGluR5 and DISC1 in the postsynaptic density fraction. Journal of Neuroscience, 31 (45). pp. 16194-16207. ISSN 0270-6474. Download
Khoshnan, Ali and Patterson, Paul H. (2011) The role of IkB kinase complex in the neurobiology of Huntington's disease. Neurobiology of Disease, 43 (2). pp. 305-311. ISSN 0969-9961. Download
Patterson, Paul H. (2011) Maternal infection and immune involvement in autism. Trends in Molecular Medicine, 17 (7). pp. 389-394. ISSN 1471-4914 . Download
Hsiao, Elaine Y. and Patterson, Paul H. (2011) Activation of the maternal immune system induces endocrine changes in the placenta via IL-6. Brain, Behavior, and Immunity, 25 (4). pp. 604-615. ISSN 0889-1591 . Download
Patterson, Paul H. (2011) Modeling autistic features in animals. Pediatric Research, 69 (5). 34R-40R. ISSN 0031-3998. Download
Southwell, Amber L. and Patterson, Paul H. (2011) Gene therapy in mouse models of Huntington disease. Neuroscientist , 17 (2). pp. 153-162. ISSN 1073-8584 . Download
Brown, Alan S. and Patterson, Paul H. (2011) Maternal infection and schizophrenia: Implications for prevention. Schizophrenia Bulletin, 37 (2). pp. 284-290. ISSN 0586-7614 . Download
Southwell, Amber L. and Bugg, Charles W. and Kaltenbach, Linda S. and Dunn, Denise and Butland, Stefanie and Weiss, Andreas and Paganetti, Paolo and Lo, Donald C. and Patterson, Paul H. (2011) Perturbation with intrabodies reveals that calpain cleavage Is required for degradation of Huntingtin Exon 1. PLoS ONE, 6 (1). Art. No. e16676. ISSN 1932-6203. Download