Gholson J. Lyon
M.D., Weill Cornell Medical College, 2004
Ph.D., Rockefeller University, 2003
Biochemistry, amino-terminal acetylation of proteins, human genetics, neuropsychiatric diseases, whole genome sequencing
The Lyon laboratory takes an integrated approach to understanding the pathophysiology of severe neuropsychiatric disorders. This includes using technologies such as whole genome sequencing, induced pluripotent stem cells and deep brain stimulation to investigate and/or perturb these conditions. We focus on the discovery of families with rare diseases and/or increased prevalence for syndromes such as intellectual disability, autism, Tourette syndrome and schizophrenia. Once we identify mutations that likely contribute to a disease, we undertake detailed functional studies of these mutations and the biological processes affected.
As an example of this, we are currently elaborating in detail the mechanistic basis of a new rare disease that we described in 2011. This is the first human disease involving a defect in the N-terminal acetylation of proteins, a common (yet vastly understudied) modification of eukaryotic proteins carried out by N-terminal acetyltransferases (NATs). We are calling this disease Ogden Syndrome, in honor of where the first family resides in Ogden, Utah. We are using several different cellular model systems, including yeast and mammalian cells, to better understand the disease pathophysiology and the basic processes of N-terminal acetylation.
The Lyon lab has a long-term research interest in the scientific problem of how genetic background and environmental perturbation influence phenotypic differences, particularly in severe mental illness. This has led us to efforts involving neuromodulation, namely investigating the effects of deep brain stimulation for treatment-refractory obsessive compulsive disorder (OCD).
Please visit Gholson's Lab home page.
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 Genet. 89: 28–43.