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Gholson Lyon

Assistant Professor
M.D., Weill Cornell Medical College, 2004
Ph.D., Rockefeller University, 2003


Contact
glyon@cshl.edu
(516) 422-4087 (p)
  Lyon Lab Website
My group focuses on human genetics and genomic medicine, with an emphasis on diseases with severe neuropsychiatric manifestations.  We collect large family pedigrees and use whole-genome sequencing to define mutations that correlate with the syndromes.  We then undertake detailed functional characterization of these mutations to discover fundamental new biology.

Gholson Lyon’s lab focuses on analyzing human genetic variation and its role in severe neuropsychiatric disorders and rare diseases, including Tourette syndrome, attention-deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), intellectual disability, autism, and schizophrenia. By recruiting large groups of related individuals living in the same geographic location (e.g., Utah), Lyon’s lab can study the breadth and depth of genetic variants in a similar environmental background. Using the exome—the parts of the genome that code for protein—and whole-genome sequencing, his lab looks for mutations that segregate with syndromes in the various populations. A second focus of the Lyon lab is to study the mechanistic basis of a new rare disease that they described in 2011. This is the first human disease involving a defect in the amino-terminal acetylation of proteins, a common modification of eukaryotic proteins carried out by amino-terminal acetyltransferases (NATs). The team has been using several different cellular model systems to better understand the disease pathophysiology and the basic process of amino-terminal acetylation. This year, Lyon collaborated with a team of researchers from other universities and companies to use precision medicine to successfully treat a patient with severe OCD. His symptoms were treated with deep brain stimulation, and the team used whole-genome sequencing to try to understand the molecular basis of his disease. The patient experienced significant relief from his symptoms and his quality of life returned, suggesting that similar methods may hold tremendous promise in the future.

O’Rawe, J.A., Fang, H., Rynearson, S., Robison, R., Kiruluta, E.S., Higgins, G., Lyon, G.J., et al. 2013. Integrating precision medicine in the study and clinical treatment of a severely mentally ill person. Peer  J. 1: eCollection.

O'Rawe, J., Jiang, T., Sun, G., Wu, Y., Wang, W., Hu, J., Lyon, G.J. et al. 2013. Low concordance of multiple variant-calling pipelines: practical implications for exome and genome sequencing. Genome Medicine 5: 28.

Lyon, G.J., and Wang, K. 2012. Identifying disease mutations in genomic medicine settings: current challenges and how to accelerate progress. Genome Med.  4: 58.

Lyon, G.J. Jiang, T., Van Wijk, R., Wang, W., Bodily, P., Xing, J., Tian, L., Robison, L., Clement, M., Yang, L., Zhang, P., Liu, Y., Moore, B., Glessner, J., Elia, J., Reimherr, F., van Solinge, W., Yandell, M., Hakonarson, H., Wang, J.,  Johnson, W.E., Wei, Z. and Wang, K.. 2011. Exome Sequencing and Unrelated Findings in the context of Complex Disease Research: Ethical and Clinical Implications. Discov. Med . 12: 41­–55. 

Rope, A.F., Wang, K., Evjenth, R., Xing, J., Johnston, J.J., Swensen, J.J., Johnson, W.E., Moore, B., Huff, C.D., Bird, L.M., Carey, J.C., Opitz, J.M., Stevens, C.A, Jiang, T., Schank, C., Fain, H.D., Robison, R., Dalley, B., Chin, S., South, S.T., Pysher, T.J., Jorde, L.B., Hakonarson, H., Lillehaug, J.R., Biesecker, L.G., Yandell, M., Arnesen, T., and Lyon, G.J. 2011. Using VAAST to Identify an X-Linked Disorder Resulting in Lethality in Male Infants Due to N-Terminal Acetyltransferase Deficiency.  American Journal of Human Genet89: 28–43.

Archived Publications
Stanley Institute
Our lab is interested in the pathophysiology of severe neuropsychiatric disorders. We use whole genome sequencing, induced pluripotent stem cells and deep brain stimulation to perform detailed functional studies of gene mutations that we have identified in families with increased prevalence of intellectual disability, autism, Tourette syndrome and schizophrenia.