Our lab is focused on understanding the role of genetic variation on disease outcomes. We employ quantitative and functional tools, in a variety of model organisms, to study how genetic variation impacts basic cellular traits important to human health. Our work in model organisms will help to model and to inform studies of genetic variation observed in the human population. We hope to identify variation in the human population that can lead to more precise, personalized therapies.
Genetic variation is a powerful, unbiased tool to uncover novel aspects of gene networks. We are using natural variation to understand how endoplasmic reticulum (ER) stress varies among individuals in a population and what this means for disease variability. To do this, we are using the mouse Collaborative Cross to uncover the genetic architecture underlying this important cellular response. We are also utilizing Drosophila, mouse, and cell culture studies to understand the function of genes that contribute to variability in the ER stress response. Finally, we are taking advantage of natural genetic variation to identify novel modifiers of Mendelian diseases.
Chow Lab Webpage: www.chowlab.org
References to Publications:
Chow CY, Avila F, Wolfner MF, Clark AG. Induction of excessive endoplasmic reticulum stress in the Drosophila male accessory gland results in infertility. PLoS ONE. 10(3): (2015).
Chow CY, Wang X, Riccardi D, Wolfner MF, Clark AG. The genetic architecture of the genome-wide transcriptional response to ER stress in the mouse. PLoS Genet. 11(2): (2015).
Chow CY, Wolfner MF, Clark AG. Using natural variation in Drosophila to discover previously unknown endoplasmic reticulum stress genes. PNAS. 110(22): 9013-9018 (2013).
Chow CY, Wolfner MF, Clark AG. A large neurological component to genetic differences underlying biased sperm use in Drosophila. Genetics. 193(1):177-8 (2013).
Lenk GM, Ferguson CJ, Chow CY, Jin N, Jones JM, Grant AE, Zolov SN, Winters JJ, Giger RJ, Dowling JJ, Weisman LS, Meisler MH. Pathogenic mechanism of the FIG4 mutation responsible for Charcot-Marie-Tooth disease CMT4J. PLoS Genet. Jun 7(6) (2011).
Im KM, Kirchhoff T, Wang X, Green T, Chow CY, et al. Haplotype Structure in Ashkenazi Jewish BRCA1 and BRCA2 Mutation Carriers. Hum Genet. 130(5):685-99 (2011).
Chow CY, Wolfner MF, Clark AG. The Genetic Basis for Male x Female Interactions Underlying Variation in Reproductive Phenotypes of Drosophila. Genetics. 186(4):1355-65 (2010).
Sirot LK, LaFlamme BA, Stitnik JL, Rubinstein CD, Avila FW, Chow CY, Wolfner, MF. Molecular social interactions: Drosophila melanogaster seminal fluid proteins as a case study. Adv. Genet. 68: 23-56 (2009).
Chow CY, Landers JE, Bergren SK, Sapp PC, Grant AE, Jones JM, Everett L, Lenk GM, McKenna-Yasek DM, Weisman LS, Figlewicz D, Brown RH, Meisler MH. Deleterious Variants of FIG4, a Phosphoinositide Phosphatase, in Patients with ALS. Am J Hum Genet. 84(1):85-8 (2009).
Jin N*, Chow CY*, Liu L, Zolov SN, Bronson R, Davisson M, Petersen JL, Zhang Y, Park S, Duex JE, Goldowitz D, Meisler MH and Weisman LS. VAC14 nucleates a protein complex that is essential for the regulation of PI(3,5)P2 levels in yeast and mouse. EMBO J. (27), 3221-34 (2008).
Zhang X, Chow CY, Sahenk Z, Shy M, Meisler M, Li J. Mutation of FIG4 causes a rapidly progressive, asymmetric neuronal degeneration. Brain 131, 1990-2001 (2008).
McKinney B, Chow CY, Meisler M, Murphy G. Exaggerated emotional behavior in mice heterozygous null for the sodium channel Scn8a (Nav1.6). Genes, brain, and behavior 7 (6), 629-38 (2008).
Zhang Y, Zolov S, Chow CY, Slutsky S, Richardson S, Piper R, Yang B, Nau J, Westrick R, Morrison S, Meisler M, Weisman L. Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol 3,5-bisphosphate, results in neurodegeneration in mice. PNAS 104 (44), 17518-23 (2007).
Chow CY, Zhang Y, Dowling J, Jin N, Adamska M, Shiga K, Szigeti K, Shy M, Li J, Zhang X, Lupski J, Weisman L, Meisler M. Mutation of FIG4 causes neurodegeneration in the pale tremor mouse and patients with CMT4J. Nature 448 (7149), 68-72 (2007).