Brian O'Roak, Ph.D.
- Professor of Molecular and Medical Genetics, School of Medicine
- Molecular and Medical Genetics Graduate Program, School of Medicine
- Neuroscience Graduate Program, School of Medicine
- Graduate Program in Biomedical Sciences, School of Medicine
Biography
I’m originally from California’s Central Valley. After earning a B.S. in Biology at CSU Fresno, I did my PhD studies at Yale University working with Dr. Matthew W. State in the Department of Genetics. I then went on for postdoctoral training in the Department of Genome Sciences at the University of Washington, under Drs. Evan E. Eichler and Jay Shendure. I joined the MMG faculty in Fall 2013.
My goal is to understand the molecular basis of neurodevelopmental disorders (NDDs) and have these fundamental insights translate into meaningful clinical interventions. My pioneering work in the last decade has focused on developing and implementing new research paradigms and technologies that challenge the genetic intractability of complex NDDs, especially autism spectrum disorder (ASD). Through these studies, and similar efforts by others, ~100 different genes are no longer merely ‘candidate’ genes for ASD risk, but are now ‘known’ genes based on their recurrent disruption by de novo mutations.
Defining the molecular mechanisms that underlie autism requires not only identification of critical genetic risk factors, but also understanding how they interact within a complex and developing system. In addition to our gene discovery efforts, our lab is now building a new paradigm that incorporates many different patient-specific mutations in a multitude of models with complementary strengths and weaknesses. Advances in genome editing, induced pluripotent stem cells (iPSCs), neurogenetics, and functional genomics have made this patient-specific approach feasible. Furthermore, we are focusing on mutations in genes that are master regulators of key biologic networks provides an avenue for reducing the phenotypic complexity of autism, biomarker discovery, and targeted personalized therapies that will have impact beyond a single risk gene.
Education and training
-
Degrees
- Ph.D., 2009, Yale University
Memberships and associations:
- American Society of Human Genetics
- Society for Neuroscience
Areas of interest
- Autism
- Neurodevelopmental disorders
- Genetics/genomics
- Stem cells
- Developmental neuroscience
Publications
Publications
Detailed phenotyping of Tbr1-2A-CreER knock-in mice demonstrates significant impacts on TBR1 protein levels and axon development
Autism ResearchNovel recruitment approaches and operational results for a statewide population Cohort for cancer research
Journal of Clinical and Translational ScienceReturn of genetic research results in 21,532 individuals with autism
Genetics in MedicineAerosol delivery of SARS-CoV-2 human monoclonal antibodies in macaques limits viral replication and lung pathology
Nature communicationsPopulation screening shows risk of inherited cancer and familial hypercholesterolemia in Oregon
American Journal of Human GeneticsCas12a-Capture
CRISPR JournalImputing cognitive impairment in SPARK, a large autism cohort
Autism ResearchIntegrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes
Nature geneticsShared and Distinct Functional Effects of Patient-Specific Tbr1 Mutations on Cortical Development
Journal of NeuroscienceValidation of Autism Diagnosis and Clinical Data in the SPARK Cohort
Journal of autism and developmental disordersAutism and attention-deficit/hyperactivity disorders and symptoms in children with neurofibromatosis type 1
Developmental Medicine and Child NeurologyBrief Report
Journal of autism and developmental disordersEarly Pandemic Experiences of Autistic Adults
Autism ResearchHigh-content single-cell combinatorial indexing
Nature biotechnologyNeutralization of SARS-CoV-2 variants by convalescent and BNT162b2 vaccinated serum
Nature communicationsRare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders
Genome MedicineRecent ultra-rare inherited variants implicate new autism candidate risk genes
Nature geneticsAn Integrated Deep-Mutational-Scanning Approach Provides Clinical Insights on PTEN Genotype-Phenotype Relationships
American Journal of Human GeneticsBeliefs in vaccine as causes of autism among SPARK cohort caregivers
VaccineClinical Phenotypes of Carriers of Mutations in CHD8 or Its Conserved Target Genes
Biological PsychiatryExcess of de novo variants in genes involved in chromatin remodelling in patients with marfanoid habitus and intellectual disability
Journal of medical geneticsLarge-scale targeted sequencing identifies risk genes for neurodevelopmental disorders
Nature communicationsPsychiatric and Medical Profiles of Autistic Adults in the SPARK Cohort
Journal of autism and developmental disordersExome sequencing of 457 autism families recruited online provides evidence for autism risk genes
npj Genomic MedicineA Saturation Mutagenesis Approach to Understanding PTEN Lipid Phosphatase Activity and Genotype-Phenotype Relationships
American Journal of Human GeneticsHighly scalable generation of DNA methylation profiles in single cells
Nature biotechnologyExonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder
American Journal of Human Genetics