Timothy W. Yu, MD, PhD

Translational genomic medicine, human gene knockouts in autism.

The Yu Lab leads genome-wide and world-wide searches for rare, familial, single-gene causes of autism, to offer insight into its genetic architecture and to understand neurobiological causes and possible treatments. A major project is to partner with the Autism Sequencing Consortium to conduct large-scale screens for mutations in whole exome sequencing data from thousands of cases and tens of thousands of controls. We focus in particular on biallelic gene knockouts (i.e., impacting both copies of a gene), and have uncovered a striking enrichment of such knockouts in individuals with autism, especially in girls. We are pursuing several candidate genes arising from such analyses, including several implicating targets of special neurobiological interest like glutamatergic and serotonergic signaling.

Our laboratory is characterizing several additional novel human neurologic syndromes that impact brain development and function, discovering links to interesting neurobiological pathways like axon guidance, cholesterol biosynthesis, and nitric oxide signaling.

In addition to basic discovery, we are contributing to efforts to further models for integrating genomic diagnostics and discovery into pediatric care. Representative projects in this area include bringing genome sequencing to the bedside care of sick patients in the NICU, and evaluating genome sequencing as a replacement for newborn screening. The story about Dr Yu’s group’s successful diagnosis of a rare genetic syndrome and development of a novel, customized medicine for that orphan disease is featured in the “Novel Therapies” section of this site’s Research page.

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