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Institute of Molecular Medicine

Laboratory of Timothy P. York, PH.D.

York

Research Projects

The focus of the York Lab is the development and application of a wide variety of statistical-genetic methods ranging from genetically informative twin and family studies to whole genome studies including gene expression, proteomic, GWAS and epigenetic platforms. Examples include the application of data mining techniques to genetic association data, increasing the statistical power in genetic association tests, DNA methylation microarray analyses, and extension of existing genetic methods for genomewide analyses.

Recently the York lab spearheaded the creation of the VIMM/HMG Data Science Lab to foster research innovation, collaboration, and improve efficiency in the analytic exercise of genomic data. The NIH has recently highlighted the need to address the issue of reproducibility in science reporting and how to enhance transparency. The DSL brings together VCU experts in the areas of Genomics, Biostatistics, Computer Science and Bioinformatics with the goal of providing consultation and collaboration opportunities to develop data solutions for VIMM/HMG faculty and students. The theory and practice of data science is rapidly developing and providing educational instruction across the VCU School of Medicine on best practices for reproducible research is a key feature of the DSL.

The primary research phenotype in the York Lab focuses on the contribution of genetic and environmental factors to preterm birth (PTB). Despite the high prevalence and marked racial disparity in prematurity rates relatively very little genetic epidemiology has been attempted. Most of our research thus far in this area has been extending twin and family methods to separate this genetic covariation. Until recently it was largely considered that only the mother’s genome contributed to the onset of labor. Our publications have provided evidence that it is both fetal and maternal genetic factors that contribute to variation in PTB. Importantly, it is mainly environmental factors that account for racial differences in PTB risk. Ongoing projects funded by the NIMHD, Burroughs Wellcome Fund and the Brain & Behavior Research Foundation seek to understand the epigenetic, genetic and environmental basis for this PTB health disparity. Utilizing longitudinal pregnancy data from the VCU Pregnancy, Race, Environment & Gene (PREG) study, the overall objective is to build etiologically informed causal models to test the extent environmental influences on PTB are mediated by changes in genomewide DNA methylation patterns. A replication study is currently underway utilizing a similar longitudinal dataset from the Global Alliance for the Prevention of Preter Birth and Stillbirth (GAPPS).

Laboratory members and collaborators

Dana Lapato
Ph.D. Student

Sara Wagner, RN
Research Nurse

Key Publications

Enga RM, Rice AC, Weller P, Subler MA, Lee D, Hall CP, Windle JJ, Beardsley PM, van den Oord EJ, McClay JL. Initial characterization of behavior and ketamine response in a mouse knockout of the post-synaptic effector gene Anks1b.  Neuroscience Letters. 2017 Feb 22;641:26-32. PMCID: PMC5305419

Jariwala N, Rajasekaran D, Mendoza RG, Shen XN, Siddiq A, Akiel MA, Robertson CL, Subler MA, Windle JJ, Fisher PB, Sanyal AJ, Sarkar D. Oncogenic role of SND1 in development and progression of hepatocellular carcinoma. Cancer Res. 2017 Jun 15;77(12):3306-3316. PMCID: PMC5488274.

Srivastava J, Robertson CL, Ebeid K, Dozmorov M, Rajasekaran D, Mendoza R, Siddiq A, Akiel MA, Jariwala N, Shen XN, Windle JJ, Subler MA, Mukhopadhyay ND, Giashuddin S, Ghosh S, Lai Z, Chen Y, Fisher PB, Salem AK, Sanyal AJ, Sarkar D. A novel role of astrocyte elevated gene-1 (AEG-1) in regulating non-alcoholic steatohepatitis (NASH). Hepatology. 2017 Aug;66(2):466-480. PMCID: PMC5519412.

Zhang Y, Liu H, Li W, Zhang Z, Zhang S, Teves ME, Stevens C, Foster JA, Campbell GE, Windle JJ, Hess RA, Pazour GJ, Zhang Z. Intraflagellar transporter protein 140 (IFT140), a component of IFT-A complex, is essential for male fertility and spermiogenesis in mice. Cytoskeleton, Dec 2017 (Epub ahead of press).

Akiel M, Guo C, Li X, Rajasekaran D, Mendoza RG, Robertson CL, Jariwala N, Yuan F, Subler MA, Windle J, Garcia DK, Lai Z, Chen HH, Chen Y, Giashuddin S, Fisher PB, Wang XY, Sarkar D. IGFBP7 Deletion Promotes Hepatocellular Carcinoma. Cancer Res. 2017, in press.

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