University of Southern California

USC Neuroscience

Daniel B. Campbell

Assistant Professor,
Psychiatry & the Behavioral Sciences
Zilkha Neurogenetic Institute

Research Topics

  1. Genetics of neuropsychiatric disorders, including autism and schizophrenia
  2. Epigenetic mechanisms of neuropsychiatric disorder risk
  3. Cellular functions of genetic and epigenetic variants that contribute to neuropsychiatric disorders
  4. Co-occurring medical conditions in autism
  5. Pharmacogenetics - using genetic information to predict most effective treatment strategies

Research Overview

My laboratory focuses on defining functional genetic variants that contribute to the etiology and treatment effectiveness of autism and schizophrenia. The long-term goals of these studies are to better understand the causes of the disorders and to improve the ability to treat them on an individualized basis. Genetic analyses are critical for determining the genes that contribute to autism and schizophrenia. However, the identification of disorder-associated genes is only the first step in determining the mechanisms by which dysfunction of the encoded proteins contributes to disorder etiology and, eventually, developing biologically-sound treatment options. My laboratory will integrate the results of unbiased whole-genome approaches with an understanding of neurobiological mechanisms to develop hypothesis-driven candidate gene approaches to improve the treatment of neurodevelopmental disorders.

Treatment options for schizophrenia include a number of different antipsychotic medications, each of which can be effective in a subset of patients. Based on gene expression arrays, genetic association analyses, and functional studies, it was determined that the gene encoding Regulator of G-protein Signaling 4 (RGS4) contributes to schizophrenia risk. Because RGS4 regulates activity of the same receptors that are targeted by antipsychotic medications, we hypothesized that variants of the RGS4 gene may also predict which antipsychotic drugs would be most effective for individual patients. We showed that RGS4 genotype does predict the effectiveness of antipsychotic medications. Continuing work in my laboratory seeks to determine how these genetic variants influence RGS4 expression in the brain and what other gene variants may also contribute to prediction of antipsychotic medication effectiveness in individual patients.

Autism is a complex neurodevelopmental disorder that often presents with co-occurring gastrointestinal or immune dysfunctions. We have taken the approach that there are several different types of autism, and that the genetic contributions to autism risk may be more obvious after stratifying groups with these co-occurring conditions. We showed that a functional variant of the gene encoding the MET receptor tyrosine kinase is strongly associated with autism in a subset of patients who also have gastrointestinal conditions. Because the MET receptor tyrosine kinase is a key regulator of immune responsiveness, which may influence both brain development and gastrointestinal function, my laboratory is now interested in how MET protein dysregulation in the immune system may contribute to autism risk in a subset of patients. Together with collaborators, my laboratory has generated data indicating that the functional variant in the MET gene is associated with an immune biomarker of autism risk. We are now pursuing studies that will help to define the role of the MET receptor in immune function, and how a deficit in MET expression in the immune system may contribute to autism risk. The goal of these studies is to find, for at least a subset of patients, effective treatment options for autism.

Contact Information

E-mail:
dbcampbe@usc.edu
Mailing Address:
Zilkha Neurogenetic Institute
USC Keck School of Medicine
1501 San Pablo St. ZNI 407
Los Angeles, CA 90033
Office Location:
ZNI 339
Office Phone:
(323) 442-2979
Lab Location:
ZNI 407

Education

  • BS, Westminster College
  • PhD, Penn State University

Selected Publications

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Campbell, D.B. (2010). Advances and challenges in the genetics of autism.  FOCUS: The American Psychiatric Association Journal of Lifelong Learning in Psychiatry. In Press.

Campbell, D.B., Warren, D., Sutcliffe, J.S., Lee, E.B., and Levitt, P. (2010).  Association of MET with social and communication phenotypes in individuals with autism spectrum disorder. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 153B: 438-446.

Buie, T.M., Campbell, D.B., Fuchs, G.J., Furuta, G.T., Levy, J., Van de Water, J., Whitaker, A.H., Atkins, D., Bauman, M.L., Beaudet A.L., Carr, E.G., Gershon, M.D., Hyman, S.L., Jirapinyo, P., Jyonouchi, H., Kooros, K., Kushak, R., Levitt, P., Levy, S.E., Lewis, J.D., Murray, K.F., Natowicz, M.R., Sabra, A., Wershil, B.K., Weston, S.C., Zeltzer, L., and Winter, H. (2010). Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with autism spectrum disorders: a consensus report.  Pediatrics. 125: S1-S18.

Levitt, P and Campbell, D.B. (2009).  The genetic and neurobiological compass points toward common signaling dysfunctions in autism spectrum disorders. Journal of Clinical Investigation. 119: 747-754.

Campbell, D.B., Buie, T.M., Winter, H., Bauman, M., Sutcliffe, J.S., Perrin, J.M., and Levitt, P. (2009). Distinct genetic risk based on association of MET in families with co-occurring autism and gastrointestinal conditions. Pediatrics. 123: 1018-1024.

Campbell, D.B. (2009). When linkage signal for autism MET candidate gene. European Journal of Human Genetics.17: 699-700.

Campbell, D.B., Li, C., Sutcliffe, J.S., Persico, A.M., and Levitt, P. (2008). Genetic evidence implicating multiple genes in the MET receptor tyrosine kinase pathway in autism spectrum disorder. Autism Research. 1: 159-168.

Campbell, D.B., Ebert, P.J., Skelly, T., Stroup, T.S., Lieberman, J.A., Levitt P., and Sullivan P.F. (2008). Ethnic stratification of the association of RGS4 with antipsychotic treatment response in schizophrenia. Biological Psychiatry. 63: 32-41.

Campbell, D.B., D'Oronzio, R., Garbett, K., Ebert, P.J., Mirnics, K., Levitt, P., and Persico, A.M. (2007). Disruption of cerebral cortex MET signaling in autism spectrum disorder. Annals of Neurology. 62: 243-250.

Campbell, D.B., Sutcliffe, J.S., Ebert, P.J., Militerni, R., Bravaccio, C., Trillo, S., Elia, M., Schneider, C., Melmed, R., Sacco, R., Persico, A.M., and Levitt, P. (2006). A genetic variant that disrupts MET transcription is associated with autism. Proceedings of the National Academy of Sciences, USA. 103: 16834-16839.