James Waschek, Ph.D.
Work Phone Number:
635 Charles E. Young Dr. South
Los Angeles, CA 90095
UCLA Psychr & Biobehav Sci
635 S. Charles E. Young Dr
BOX 957332, NRB 345
Los Angeles, CA 90095
Psychiatry and Biobehavioral Sciences
Professor in Residence,
Semel Institute for Neuroscience and Human Behavior
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Brain Research Institute
JCCC Signal Transduction and Therapeutics Program Area
A Short Biography:
Research in the Waschek laboratory has centered mainly on the biological actions of neuropeptides in the VIP and PACAP family. These peptides are rather unique because they function not only as neurotransmitters, but also as potent growth factors and immunomodulators. Recent large scale genetic studies have linked mutations in the genes encoding these peptides and receptors to schizophrenia and post-traumatic stress disorder (PTSD), diseases now believed to have developmental/plasticity underpinnings. Current projects with long-standing funding in the laboratory have utilized animal models of multiple sclerosis, perinatal brain inflammation, and Parkinson's Disease. In more recently funded projects, we have begun to employ studies of fear conditioning and extinction and circadian rhythms to help understand the mechanistic links of these molecules to PTSD, schizophrenia, and autism. As critical reagents for these investigations, the laboratory has generated several neuropeptide-deficient and reporter mice, and utilized several transgenic and conditional knockout mouse strains that alter the phenotype of astrocytes and myeloid cells. In addition, we employ a wide variety of standard and specialized approaches, including viral gene delivery, fluorescence microscopy, FACS, and tissue culture. More detailed information is available at http://www.mrrc.npi.ucla.edu/JWASCHEK/.
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 Multiple Sclerosis Society and the National Brain Tumor Society. 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.
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.),
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
Annals of neurology,
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.
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,
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.),
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
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
Journal of neuroscience research,
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,
Lelievre V, Favrais G, Abad C, Adle-Biassette H, Lu Y, Germano P M, Cheung-Lau G, Pisegna J R, Gressens P, Lawson G, Waschek J A
Gastrointestinal dysfunction in mice with a targeted mutation in the
gene encoding vasoactive intestinal polypeptide: a model for the study
of intestinal ileus and Hirschsprung's disease.
Said Sami I, Hamidi Sayyed A, Dickman Kathleen G, Szema Anthony M, Lyubsky Sergey, Lin Richard Z, Jiang Ya-Ping, Chen John J, Waschek James A, Kort Smadar
Moderate pulmonary arterial hypertension in male mice lacking the
vasoactive intestinal peptide gene.
Szema Anthony M, Hamidi Sayyed A, Lyubsky Sergey, Dickman Kathleen G, Mathew Suni, Abdel-Razek Tarek, Chen John J, Waschek James A, Said Sami I
Mice lacking the VIP gene show airway hyperresponsiveness and airway
inflammation, partially reversible by VIP.
American journal of physiology. Lung cellular and molecular physiology,
Girard Beatrice A, Lelievre Vincent, Braas Karen M, Razinia Tannaz, Vizzard Margaret A, Ioffe Yevgeniya, El Meskini Rajaa, Ronnett Gabriele V, Waschek James A, May Victor
Noncompensation in peptide/receptor gene expression and distinct
behavioral phenotypes in VIP- and PACAP-deficient mice.
Journal of neurochemistry,
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,
Armstrong Brian D, Hu Zhongting, Abad Catalina, Yamamoto Miya, Rodriguez Williams I, Cheng Jennifer, Tam Jimmy, Gomariz Rosa P, Patterson Paul H, Waschek James A
Lymphocyte regulation of neuropeptide gene expression after neuronal
Journal of neuroscience research,