The overall goal of the Vawter Functional Genomics Laboratory is to test clinical samples from healthy controls and subjects with a psychiatric diagnosis for establishing reference levels for each group. A variety of tests are run using techniques including genetics, gene expression, and protein. Samples that have been used in the laboratory are generally postmortem brain samples, cultured lymphoblastoid cell lines, and whole blood samples. Pathophysiology and biomarker testing is the aim of the research which may lead to discovery of novel candidate drug targets for treatment and assessment of psychiatric disorders. Disorders that are studied in the laboratory are:
Our laboratory works closely with the UCI Brain Bank and in turn closely with the Orange County and San Diego County Coroner’s Offices.
Laboratory funding sources are:
- Pritzker Neuropsychiatric Disorders Consortium (William Bunney-UCI Site Director, Marquis Vawter Co-Investigator)
- NIMH Conte Center Grant (William Bunney – PI, Marquis Vawter – Co Investigator)
- Penzner Foundation (Department and laboratory unrestricted gift)
- Allen Institute for Brain Science
- Della Martin Fellowship award (Adolfo Sequeira through Dr. William Bunney Della Martin Chair of Psychiatry)
- NARSAD Young Investigator Award (Adolfo Sequeira-Young Investigator PI, Marquis Vawter – Mentor)
- NIMH- Grant Number: 1R01MH085801 – 01, Mitochondrial Variants in Schizophrenia and Bipolar Disorder (Marquis Vawter, PI)
The Vawter Functional Genomics Laboratory is located in the William Gillespie Neuroscience Building at University of California, Irvine under the Department of Psychiatry and Human Behavior, and was started in February 2001. The lab is directed by Dr. Marquis Vawter and managed by Brandi Rollins.
A collaboration with the Allen Institute of Brain Science, and the Functional Genomics Laboratory has been granted IRB approval November 25, 2008 titled ‘Postmortem Specimen Collection for An Atlas of Gene Expression in Whole Human Brain’. The purpose of the project is the collection of high-quality clinically characterized postmortem whole brain specimens from normal controls. These brains will be used by the Allen Institute in the creation a comprehensive multimodal human brain atlas that surveys the entire human genome throughout the brain and shows which genes are turned on, or expressed, in which brain structures. Specifically, the goal of the project is to create a detailed three-dimensional human brain atlas that includes quantitative data for all genes for all brain structures at the anatomic structure level. As part of this effort, the Institute will (1) create a series of high-resolution annotated atlases from whole human brains; (2) generate quantitative readouts of structure-specific gene expression data by isolating genetic material (RNA) from carefully dissected anatomic regions and analyzing it on microarrays; and (3) develop a series of Web-based tools for visualizing, accessing and mining the data. In addition to microarray gene expression data, 3D MRI data, detailed histological data, and in situ hybridization-based gene expression data will be integrated into the Allen Human Brain Atlas dataset so that users may assess gene expression in its anatomic and cytoarchitectural context, possibly helping researchers to better connect anatomic and functional information with underlying genetic information. While various human brain atlases exist in print or online form, none of the currently available atlases combine all of the data modalities into a single resource with 3D representation of the data. All data and tools will be made freely available to the scientific community on the Web in order to encourage widespread use and scientific collaboration.
An active and nascent biomarker program was started in the laboratory. Current biomarker projects involve studying healthy controls for circadian fluctuations in lymphocyte gene expression. A clinical project in collaboration with Dr. John Kelsoe, Dr. Joseph Wu, Dr. Blynn Bunney, and Dr. William Bunney is focused on sleep deprivation as an adjunct rapid antidepressant and using lymphocyte gene expression to predict responders. Comparisons of blood and brain gene expression have been conducted.
An active genetics study focused on an isolated population in the Central Valley of Costa Rica in collaboration with Dr. Lynn DeLisi, Dr. William Bunney, and Dr. William Byerley is underway. The laboratory is genotyping NRG1 (neuregulin 1) as a candidate gene for schizophrenia in Costa Rica samples. Sample ascertainment is directed by Andrea Fainardi-Mesén, M.D.
A recent project comparing schizophrenia and bipolar disorder found 78 genes that were dysregulated in both disorders in the DLPFC (PDF). This project demonstrated that both mental disorders share common gene expression alterations in pathways involving cellular apoptosis and immune dysregulation in brain
(Table 3 of pathway analysis, reproduced from Biol Psychiatry. 2008 Jul 15;64(2):89-97).
This article was the subject of a press release by the Society of Biological Psychiatry.
Recently completed grant projects:
- UCI GCRC Sleep Deprivation and Biomarkers (Vawter – PI)
- NIMH Biomarker Grant (Marquis Vawter – PI)
- Stanley Foundation Medical Research Grant (Marquis Vawter – PI)