Research Projects
Under Dr. Knowles’ leadership, the laboratory is pursuing:
Transcriptional Atlas of Human Brain Development. The NIMH-funded project is a collaboration between USC, Yale University, and the Allen Institute for Brain Science to determine how differences in gene expression in distinct brain regions contribute to development of the human brain.
Researchers at Yale and USC will sequence transcripts in 16 brain regions at 11 key developmental stages from over 900 samples. The Allen Institute will provide more detailed analysis at the cellular level in a subset of samples. High resolution reference images and detailed cellular information will be available in an online multi-modal resource that the research community can query to learn how specific risk genes for mental disorders affect brain development or which risk gene variants influence gene expression across development.
Discovery of genetic variants that predispose individuals to psychiatric disorders through the conduct of genome-wide association studies, exomic sequencing, and/or high-throughput genomic sequencing in:
- Panic Disorder
- Obsessive-Compulsive Disorder (OCD)
- Nicotine Addiction
- Schizophrenia
- Bipolar Disorder
- Major Depression
The Center owns multiple platforms for performing paired-end high-throughput sequencing and robotic workstations to facilitate high throughput analyses. Located in the Zilkha Neurogenetic Institute (ZNI), the Center has access to ZNI shared facilities and equipment. Through the USC Core Genomics Laboratory, a full Illumina BeadLab System is available for genome wide association studies and other applications.
Development of well-characterized population samples with major psychiatric disorders, including schizophrenia and bipolar disorder.
The NIMH-funded Genomic Psychiatry Cohort at USC (PIs: Drs. Carlos and Michele Pato) includes biological samples and diagnostic data on 10,000 individuals with schizophrenia and 10,000 unaffected controls. Through USC’s participation in the International Cohort Collection for Bipolar Disorder (ICCBP), biological and diagnostic data also are available for thousands of participants with bipolar disorder and controls.
Drs. Pato and Knowles are members of the Zilkha Neurogenetic Institute and collaborate with other neuroscientists and statistical geneticists within the ZNI.
Development of in-vitro neural cell system models from individuals with psychiatric disorders.
Post-mortem brain tissue is neither readily available nor the ideal system with which to investigate gene and protein expression in individuals with psychiatric disorders. A novel system using neural cells derived from nasal biopsies may provide a powerful tool for such investigations.