James A. Waschek, Ph.D.

Professor, Adult Psychiatry

Psychiatry and Biobehavioral Sciences

Semel Institute for Neuroscience and Human Behavior

Biography

Dr. Waschek is a Professor of Psychiatry and Biobehavioral Science at the David Geffen School of Medicine at the University of California at Los Angeles (UCLA), and is an expert in the molecular and cellular biology and physiological actions of neuropeptides. Dr. Waschek received a Ph.D. in Pharmaceutical Chemistry in 1984 from the University of California at San Francisco, after which he took a postdoctoral position at the National Institutes of Health (NIH). In 1988 he came to UCLA, where his research has centered on three broad, but related topics: 1) CNS development, degeneration, injury, and repair, 2) neuroinflammatory conditions such as multiple sclerosis, and maternal inflammation-induced perinatal white matter disease, and 3) brain tumor pathogenesis. A past and continuing objective has been to better understand the biological roles of neuropeptides in these processes, especially the two related peptides PACAP and VIP (pituitary adenylyl cyclase activating peptide and vasoactive intestinal peptide, respectively). A major contribution in this area was his discovery first reported in 1998 that PACAP and functional PACAP receptors are highly expressed in the murine neural tube and other germinal centers, and that PACAP acts in part via cAMP and protein kinase A to regulate neural patterning and proliferation via antagonism of hedgehog signaling. Using gene targeting and other approaches, he found this interaction to be relevant not only during brain development, but also in the pathogenesis of malignant pediatric brain tumors. In other work, he has demonstrated growth factor-like actions of PACAP in the maturation of white matter (myelin) and in axon regeneration after injury. Most recently, he determined that VIP and PACAP are critically involved in inflammatory responses after nerve injury and in other pathologies such as lung and liver injury, colitis, cystitis, viral infection, and in an animal model of multiple sclerosis. These studies have revealed significant effects of PACAP and VIP PACAP loss on innate cellular responses to injury, as well as in Th1, Th2, and Th17 differentiation, regulatory T cell production, and immune cell invasion of the CNS parenchyma. Has been continuously funding for his research by the NIH since 1984, and is also currently receiving funding through major grants from the National Institutes of Health, the National Multiple Sclerosis Society, the Department of Defense, and the Simons Foundation. Dr. Waschek has served on NIH study sections almost continuously since 2006, and served as an external reviewer for the newly-formed LOWEE Institute on Tumors and Inflammation in Marburg, Germany, and a consultant for the Japanese-Israeli Scientific and Technological Cooperation Agreement in Life Sciences in the Topic of Stem Cell Research.

Tan Yossan-Var, Abad Catalina, Wang Yuqi, Lopez Robert, Waschek James A   Pituitary Adenylate Cyclase Activating Peptide Deficient Mice Exhibit Impaired Thymic and Extrathymic Regulatory T Cell Proliferation during EAE PloS one, 2013; 8(4): e61200.

Yan Yan, Zhou Xiaofeng, Pan Zui, Ma Jianjie, Waschek James A, DiCicco-Bloom Emanuel   Pro- and anti-mitogenic actions of pituitary adenylate cyclase-activating polypeptide in developing cerebral cortex: potential mediation by developmental switch of PAC1 receptor mRNA isoforms The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013; 33(9): 3865-78.

Tyagi Ethika, Agrawal Rahul, Zhuang Yumei, Abad Catalina, Waschek James A, Gomez-Pinilla Fernando   Vulnerability imposed by diet and brain trauma for anxiety-like phenotype: implications for post-traumatic stress disorders PloS one, 2013; 8(3): e57945.

Ji Haofeng, Zhang Yu, Shen Xiuda, Gao Feng, Huang Cynthia Y, Abad Catalina, Busuttil Ronald W, Waschek James A, Kupiec-Weglinski Jerzy W   Neuropeptide PACAP in mouse liver ischemia and reperfusion injury: immunomodulation via cAMP-PKA pathway Hepatology (Baltimore, Md.), 2012; 166(1): .

Waschek James A   Noggin on heaven's door: a factor that promotes the selective production of serotonergic neurons from murine embryonic stem cells and induced pluripotent stem cells Journal of neurochemistry, 2012; 122(1): 1-3.

Nobuta Hiroko, Ghiani Cristina A, Paez Pablo M, Spreuer Vilma, Dong Hongmei, Korsak Rose A, Manukyan Armine, Li Jiaxi, Vinters Harry V, Huang Eric J, Rowitch David H, Sofroniew Michael V, Campagnoni Anthony T, de Vellis Jean, Waschek James A   STAT3-mediated astrogliosis protects myelin development in neonatal brain injury Annals of neurology, 2012; 72(5): 750-65.

Abad Catalina, Tan Yossan-Var, Cheung-Lau Gardenia, Nobuta Hiroko, Waschek James A   VIP deficient mice exhibit resistance to lipopolysaccharide induced endotoxemia with an intrinsic defect in proinflammatory cellular responses PloS one, 2012; 7(5): e36922.

Abad Catalina, Gomariz Rosa, Waschek James, Leceta Javier, Martinez Carmen, Juarranz Yasmina, Arranz Alicia   VIP in inflammatory bowel disease: state of the art Endocrine, metabolic & immune disorders drug targets, 2012; 12(4): 316-22.

Ghiani Cristina A, Mattan Natalia S, Nobuta Hiroko, Malvar Jemily S, Boles Julie, Ross Michael G, Waschek James A, Carpenter Ellen M, Fisher Robin S, de Vellis Jean   Early effects of lipopolysaccharide-induced inflammation on foetal brain development in rat ASN neuro, 2011; 3(4): .

Loh Dawn H, Dragich Joanna M, Kudo Takashi, Schroeder Analyne M, Nakamura Takahiro J, Waschek James A, Block Gene D, Colwell Christopher S   Effects of vasoactive intestinal Peptide genotype on circadian gene expression in the suprachiasmatic nucleus and peripheral organs Journal of biological rhythms, 2011; 26(3): 200-9.

Alexandre David, Alonzeau Jessy, Bill Brent R, Ekker Stephen C, Waschek James A   Expression analysis of PAC1-R and PACAP genes in zebrafish embryos Journal of molecular neuroscience : MN, 2011; 43(1): 94-100.

Abad Catalina, Waschek James A   Immunomodulatory roles of VIP and PACAP in models of multiple sclerosis Current pharmaceutical design, 2011; 17(10): 1025-35.

Hirose Megumi, Niewiadomski Pawel, Tse Gary, Chi Gloria C, Dong Hongmei, Lee Alice, Carpenter Ellen M, Waschek James A   Pituitary adenylyl cyclase-activating peptide counteracts hedgehog-dependent motor neuron production in mouse embryonic stem cell cultures Journal of neuroscience research, 2011; 89(9): 1363-74.

Tan Yossan-Var, Waschek James A   Targeting VIP and PACAP receptor signalling: new therapeutic strategies in multiple sclerosis ASN neuro, 2011; 3(4): .

Dragich Joanna M, Loh Dawn H, Wang Louisa M, Vosko Andrew M, Kudo Takashi, Nakamura Takahiro J, Odom Irene H, Tateyama Sei, Hagopian Arkady, Waschek James A, Colwell Christopher S   The role of the neuropeptides PACAP and VIP in the photic regulation of gene expression in the suprachiasmatic nucleus The European journal of neuroscience, 2010; 31(5): 864-75.

Abad Catalina, Tan Yossan-Var, Lopez Robert, Nobuta Hiroko, Dong Hongmei, Phan Phu, Feng Ji-Ming, Campagnoni Anthony T, Waschek James A   Vasoactive intestinal peptide loss leads to impaired CNS parenchymal T-cell infiltration and resistance to experimental autoimmune encephalomyelitis Proceedings of the National Academy of Sciences of the United States of America, 2010; 107(45): 19555-60.

Kim Woo-Kyun, Meliton Vicente, Park Kye Won, Hong Cynthia, Tontonoz Peter, Niewiadomski Pawel, Waschek James A, Tetradis Sotirios, Parhami Farhad   Negative regulation of Hedgehog signaling by liver X receptors Molecular endocrinology (Baltimore, Md.), 2009; 23(10): 1532-43.

Tan Yossan-Var, Abad Catalina, Lopez Robert, Dong Hongmei, Liu Shen, Lee Alice, Gomariz Rosa P, Leceta Javier, Waschek James A   Pituitary adenylyl cyclase-activating polypeptide is an intrinsic regulator of Treg abundance and protects against experimental autoimmune encephalomyelitis Proceedings of the National Academy of Sciences of the United States of America, 2009; 106(6): 2012-7.

Stack Conor M, Lim Maria A, Cuasay Katrina, Stone Madeleine M, Seibert Kimberly M, Spivak-Pohis Irit, Crawley Jacqueline N, Waschek James A, Hill Joanna M   Deficits in social behavior and reversal learning are more prevalent in male offspring of VIP deficient female mice Experimental neurology, 2008; 211(1): 67-84.

Lelievre Vincent, Seksenyan Akop, Nobuta Hiroko, Yong William H, Chhith Seririthanar, Niewiadomski Pawel, Cohen Joseph R, Dong Hongmei, Flores Avegail, Liau Linda M, Kornblum Harley I, Scott Matthew P, Waschek James A   Disruption of the PACAP gene promotes medulloblastoma in ptc1 mutant mice Developmental biology, 2008; 313(1): 359-70.

Armstrong B D, Abad C, Chhith S, Cheung-Lau G, Hajji O E, Nobuta H, Waschek J A   Impaired nerve regeneration and enhanced neuroinflammatory response in mice lacking pituitary adenylyl cyclase activating peptide Neuroscience, 2008; 151(1): 63-73.

Nemetz Nicole, Abad Catalina, Lawson Greg, Nobuta Hiroko, Chhith Seririthanar, Duong Lucy, Tse Gary, Braun Jonathan, Waschek James A   Induction of colitis and rapid development of colorectal tumors in mice deficient in the neuropeptide PACAP International journal of cancer. Journal international du cancer, 2008; 122(8): 1803-9.

Niewiadomski Pawel, Coûté-Monvoisin Anne-Claire, Abad Catalina, Ngo Danny, Menezes Adrian, Waschek James A   Mice Deficient in both Pituitary Adenylyl Cyclase-activating Polypeptide and Vasoactive Intestinal Peptide Survive, but Display Growth Retardation and Sex-dependent Early Death Journal of molecular neuroscience : MN, 2008; 36(1-3): 200-7.

Lim Maria A, Stack Conor M, Cuasay Katrina, Stone Madeleine M, McFarlane Hewlet G, Waschek James A, Hill Joanna M   Regardless of genotype, offspring of VIP-deficient female mice exhibit developmental delays and deficits in social behavior International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience, 2008; 26(5): 423-34.

Studeny Simon, Cheppudira Bopaiah P, Meyers Susan, Balestreire Elena M, Apodaca Gerard, Birder Lori A, Braas Karen M, Waschek James A, May Victor, Vizzard Margaret A   Urinary bladder function and somatic sensitivity in vasoactive intestinal polypeptide (VIP)-/- mice Journal of molecular neuroscience : MN, 2008; 36(1-3): 175-87.

Loh Dawn H, Abad Catalina, Colwell Christopher S, Waschek James A   Vasoactive intestinal peptide is critical for circadian regulation of glucocorticoids Neuroendocrinology, 2008; 88(4): 246-55.

Lacombe Arnaud, Lelievre Vincent, Roselli Charles E, Muller Jean-Marc, Waschek James A, Vilain Eric   Lack of vasoactive intestinal peptide reduces testosterone levels and reproductive aging in mouse testis The Journal of endocrinology, 2007; 194(1): 153-60.

Lacombe Arnaud, Lelievre Vincent, Roselli Charles E, Salameh Wael, Lue Yan-he, Lawson Gregory, Muller Jean-Marc, Waschek James A, Vilain Eric   Delayed testicular aging in pituitary adenylate cyclase-activating peptide (PACAP) null mice Proceedings of the National Academy of Sciences of the United States of America, 2006; 103(10): 3793-8.

Aton Sara J, Colwell Christopher S, Harmar Anthony J, Waschek James, Herzog Erik D   Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons Nature neuroscience, 2005; 8(4): 476-83.

Colwell Christopher S, Michel Stephan, Itri Jason, Rodriguez Williams, Tam J, Lelievre Vincent, Hu Zhou, Liu X, Waschek James A   Disrupted circadian rhythms in VIP- and PHI-deficient mice American journal of physiology. Regulatory, integrative and comparative physiology, 2003; 285(5): R939-49.

Nicot Arnaud, Lelièvre Vincent, Tam Jimmy, Waschek James A, DiCicco-Bloom Emanuel   Pituitary adenylate cyclase-activating polypeptide and sonic hedgehog interact to control cerebellar granule precursor cell proliferation The Journal of neuroscience : the official journal of the Society for Neuroscience, 2002; 22(21): 9244-54.

Niewiadomski Pawel, Zhujiang Annie, Youssef Mary, Waschek James A   Interaction of PACAP with Sonic hedgehog reveals complex regulation of the hedgehog pathway by PKA Cellular signalling, 2013; 25(11): 2222-30.

Li Jian-Ming, Southerland Lauren, Hossain Mohammad S, Giver Cynthia R, Wang Ying, Darlak Kasia, Harris Wayne, Waschek James, Waller Edmund K   Absence of vasoactive intestinal peptide expression in hematopoietic cells enhances Th1 polarization and antiviral immunity in mice Journal of immunology (Baltimore, Md. : 1950), 2011; 187(2): 1057-65.

Ji Haofeng, Zhang Yu, Liu Yuanxing, Shen Xiu-Da, Gao Feng, Nguyen Terry T, Busuttil Ronald W, Waschek James A, Kupiec-Weglinski Jerzy W   Vasoactive intestinal peptide attenuates liver ischemia/reperfusion injury in mice via the cyclic adenosine monophosphate-protein kinase a pathway Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 2013; 19(9): 945-56.

Abad Catalina, Nobuta Hiroko, Li Jiaxi, Kasai Atsushi, Yong William H, Waschek James A   Targeted STAT3 disruption in myeloid cells alters immunosuppressor cell abundance in a murine model of spontaneous medulloblastoma Journal of leukocyte biology, 2014; 95(2): 357-67.

Marquez Paul, Bebawy David, Lelièvre Vincent, Coûté Anne-Claire, Evans Christopher J, Waschek James A, Lutfy Kabirullah   The role of endogenous PACAP in motor stimulation and conditioned place preference induced by morphine in mice Psychopharmacology, 2009; 204(3): 457-63.

Yusta Bernardo, Holland Dianne, Waschek James A, Drucker Daniel J   Intestinotrophic glucagon-like peptide-2 (GLP-2) activates intestinal gene expression and growth factor-dependent pathways independent of the vasoactive intestinal peptide gene in mice Endocrinology, 2012; 153(6): 2623-32.

Kim Kyun-Do, Srikanth Sonal, Tan Yossan-Var, Yee Ma-Khin, Jew Marcus, Damoiseaux Robert, Jung Michael E, Shimizu Saki, An Dong Sung, Ribalet Bernard, Waschek James A, Gwack Yousang   Calcium signaling via Orai1 is essential for induction of the nuclear orphan receptor pathway to drive Th17 differentiation Journal of immunology (Baltimore, Md. : 1950), 2014; 192(1): 110-22.

Vu John P, Million Mulugeta, Larauche Muriel, Luong Leon, Norris Joshua, Waschek James A, Pothoulakis Charalabos, Pisegna Joseph R, Germano Patrizia M   Inhibition of vasoactive intestinal polypeptide (VIP) induces resistance to dextran sodium sulfate (DSS)-induced colitis in mice Journal of molecular neuroscience : MN, 2014; 52(1): 37-47.

Brown T M, Colwell C S, Waschek J A, Piggins H D   Disrupted neuronal activity rhythms in the suprachiasmatic nuclei of vasoactive intestinal polypeptide-deficient mice Journal of neurophysiology, 2007; 97(3): 2553-8.

Watson M B, Nobuta H, Abad C, Lee S K, Bala N, Zhu C, Richter F, Chesselet M-F, Waschek J A   PACAP deficiency sensitizes nigrostriatal dopaminergic neurons to paraquat-induced damage and modulates central and peripheral inflammatory activation in mice Neuroscience, 2013; 240: 277-86.

Waschek J A   VIP and PACAP: neuropeptide modulators of CNS inflammation, injury, and repair British journal of pharmacology, 2013; 169(3): 512-23.

Colwell C S, Michel S, Itri J, Rodriguez W, Tam J, Lelièvre V, Hu Z, Waschek J A   Selective deficits in the circadian light response in mice lacking PACAP American journal of physiology. Regulatory, integrative and comparative physiology, 2004; 287(5): R1194-201.

Vu John P, Larauche Muriel, Flores Martin, Luong Leon, Norris Joshua, Oh Suwan, Liang Li-Jung, Waschek James, Pisegna Joseph R, Germano Patrizia M   Regulation of Appetite, Body Composition, and Metabolic Hormones by Vasoactive Intestinal Polypeptide (VIP) Journal of molecular neuroscience : MN, 2015; 56(2): 377-87.

Ago Yukio, Condro Michael C, Tan Yossan-Var, Ghiani Cristina A, Colwell Christopher S, Cushman Jesse D, Fanselow Michael S, Hashimoto Hitoshi, Waschek James A   Reductions in synaptic proteins and selective alteration of prepulse inhibition in male C57BL/6 mice after postnatal administration of a VIP receptor (VIPR2) agonist Psychopharmacology, 2015; 232(12): 2181-9.

Onaka Yusuke, Shintani Norihito, Nakazawa Takanobu, Haba Ryota, Ago Yukio, Wang Hyper, Kanoh Takuya, Hayata-Takano Atsuko, Hirai Hiroyuki, Nagata Kin-Ya, Nakamura Masataka, Hashimoto Ryota, Matsuda Toshio, Waschek James A, Kasai Atsushi, Nagayasu Kazuki, Baba Akemichi, Hashimoto Hitoshi   CRTH2, a prostaglandin D2 receptor, mediates depression-related behavior in mice Behavioural brain research, 2015; 284(12): 131-7.

Tan Yossan-Var, Abad Catalina, Wang Yuqi, Lopez Robert, Waschek James A   VPAC2 (vasoactive intestinal peptide receptor type 2) receptor deficient mice develop exacerbated experimental autoimmune encephalomyelitis with increased Th1/Th17 and reduced Th2/Treg responses Brain, behavior, and immunity, 2015; 44(12): 167-75.

Yamasaki Atsushi, Kasai Atsushi, Toi Akihiro, Kurita Maki, Kimoto Saki, Hayata-Takano Atsuko, Nakazawa Takanobu, Nagayasu Kazuki, Shintani Norihito, Hashimoto Ryota, Ito Akira, Meltzer Herbert Y, Ago Yukio, Waschek James A, Onaka Yusuke, Matsuda Toshio, Baba Akemichi, Hashimoto Hitoshi   Identification of the role of bone morphogenetic protein (BMP) and transforming growth factor-β (TGF-β) signaling in the trajectory of serotonergic differentiation in a rapid assay in mouse embryonic stem cells in vitro Journal of neurochemistry, 2015; 132(4): 418-28.

Abad Catalina, Cheung-Lau Gardenia, Coûté-Monvoisin Anne-Claire, Waschek James A   Vasoactive intestinal peptide-deficient mice exhibit reduced pathology in trinitrobenzene sulfonic acid-induced colitis Neuroimmunomodulation, 2015; 22(3): 203-12.

Wu Xiujuan, Conlin Victoria S, Morampudi Vijay, Ryz Natasha R, Nasser Yasmin, Bhinder Ganive, Bergstrom Kirk S, Yu Hong B, Waterhouse Chris C M, Buchan Allison M J, Popescu Oana E, Gibson William T, Waschek James A, Vallance Bruce A, Jacobson Kevan   Vasoactive intestinal polypeptide promotes intestinal barrier homeostasis and protection against colitis in mice PloS one, 2015; 10(5): e0125225.

Castorina Alessandro, Waschek James A, Marzagalli Rubina, Cardile Venera, Drago Filippo   PACAP interacts with PAC1 receptors to induce tissue plasminogen activator (tPA) expression and activity in schwann cell-like cultures PloS one, 2015; 10(2): e0117799.

Teuchner Barbara, Dimmer Andreas, Humpel Christian, Amberger Albert, Fischer-Colbrie Reiner, Nemeth Jozsef, Waschek James A, Kieselbach Gerhard, Kralinger Martina, Schmid Eduard, Bechrakis Nikolaos, Troger Josef   VIP, PACAP-38, BDNF and ADNP in NMDA-induced excitotoxicity in the rat retina Acta ophthalmologica, 2011; 89(7): 670-5.

Cohen Joseph R, Resnick Daniel Z, Niewiadomski Pawel, Dong Hongmei, Liau Linda M, Waschek James A   Pituitary adenylyl cyclase activating polypeptide inhibits gli1 gene expression and proliferation in primary medulloblastoma derived tumorsphere cultures BMC cancer, 2010; 10(7): 676.

Martin Bronwen, Shin Yu-Kyong, White Caitlin M, Ji Sunggoan, Kim Wook, Carlson Olga D, Napora Joshua K, Chadwick Wayne, Chapter Megan, Waschek James A, Mattson Mark P, Maudsley Stuart, Egan Josephine M   Vasoactive intestinal peptide-null mice demonstrate enhanced sweet taste preference, dysglycemia, and reduced taste bud leptin receptor expression Diabetes, 2010; 59(5): 1143-52.

Girard Beatrice M, Malley Susan E, Braas Karen M, Waschek James A, May Victor, Vizzard Margaret A   Exaggerated expression of inflammatory mediators in vasoactive intestinal polypeptide knockout (VIP-/-) mice with cyclophosphamide (CYP)-induced cystitis Journal of molecular neuroscience : MN, 2008; 36(1-3): 188-99.

Nakano Ichiro, Masterman-Smith Michael, Saigusa Kuniyasu, Paucar Andres A, Horvath Steve, Shoemaker Lorelei, Watanabe Momoko, Negro Alejandra, Bajpai Ruchi, Howes Amy, Lelievre Vincent, Waschek James A, Lazareff Jorge A, Freije William A, Liau Linda M, Gilbertson Richard J, Cloughesy Timothy F, Geschwind Daniel H, Nelson Stanley F, Mischel Paul S, Terskikh Alexey V, Kornblum Harley I   Maternal embryonic leucine zipper kinase is a key regulator of the proliferation of malignant brain tumors, including brain tumor stem cells Journal of neuroscience research, 2008; 86(1): 48-60.