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David Threadgill

Threadgill, David
David Threadgill
University Distinguished Professor, Tom and Jean McMullin Chair of Genetics, Professor of Molecular and Cellular Medicine and of Biochemistry and Biophysics
Undergraduate Education
B.S., Texas A&M University, 1983
Graduate Education
Ph.D. Texas A&M University, 1989

Areas of Research

Our laboratory uses the mouse as an experimental genetic model to investigate factors that contribute to inter-individual differences in health and disease. Ourcurrent research activities include the identification and functional characterization of alleles contributing to cancer susceptibility, the function of the Erbb gene family in development and disease, and the role of genetic variation in response to environmental stimuli. To support these investigations, we also aredeveloping new genetic tools to support mammalian systems genetic approaches to phenotypes with complex genetic and environmental etiologies.

Cancer genetics

We are focusing on colorectal, breast and kidney cancer to identify environmental factors and genetic polymorphisms contributing to differential susceptibility to the development and progression of cancer. We are also developing approaches to exploit these factors to prevent or delay cancer as well as to identify new therapies.

Epidermal growth factor receptor (Egfr)

We are using mouse models with genetically engineered or spontaneous mutations to elucidate the biological role of Egfr and other member of the Erbb gene family in vivo. These studies have lead to new insights into the role of these genes in neuronal survival and behavior, obesity, cancer and cardiovascular disease. We are currently performing mechanistic studies to identify how the Erbb genes contribute to normal and abnormal phenotypes.

Genetics of environmental responses

Just as individuals differ in their genetic constitution and disease susceptibility, they also differ in their responses toexogenous stimuli. We are using mouse models to investigate responses to environmental factors like the enteric flora of the gastrointestinal tract, diet, and toxicants like dioxin, trichloroethylene, and arsenic. The goal of these studies is to identify how individual responses to environmental factors leads to differential disease susceptibilities and methods to prevent disease in exposed individuals.

Systems genetics resources

We are participating in a large international effort to develop and exploit a new mouse genetic resources that will support the integration of genetics into systems biological analyses at the whole animal level. These efforts are based upon the Collaborative Cross, which is a unique recombinant inbred population of mice that have randomly assorted the genetic polymorphisms present in the eight founder inbred strains. A major focus of our work is the development and use of cell-based platforms for in vitro genetic studies.

Recent Publications

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  1. Sudweeks, J, Hollingsworth, B, Blondel, DV, Campbell, KJ, Dhole, S, Eisemann, JD et al.. Locally Fixed Alleles: A method to localize gene drive to island populations. Sci Rep. 2019;9 (1):15821.
    doi: 10.1038/s41598-019-51994-0. PubMed PMID:31676762. .

  2. Luo, YS, Cichocki, JA, Hsieh, NH, Lewis, L, Wright, FA, Threadgill, DW et al.. Using Collaborative Cross Mouse Population to Fill Data Gaps in Risk Assessment: A Case Study of Population-Based Analysis of Toxicokinetics and Kidney Toxicodynamics of Tetrachloroethylene. Environ. Health Perspect. 2019;127 (6):67011.
    doi: 10.1289/EHP5105. PubMed PMID:31246107. PubMed Central PMC6792382.

  3. Rogovskyy, AS, Threadgill, DW, Akimov, IA, Nebogatkin, IV, Rogovska, YV, Melnyk, MV et al.. Borrelia and Other Zoonotic Pathogens in Ixodes ricinus and Dermacentor reticulatus Ticks Collected from the Chernobyl Exclusion Zone on the 30th Anniversary of the Nuclear Disaster. Vector Borne Zoonotic Dis. 2019;19 (7):466-473.
    doi: 10.1089/vbz.2018.2318. PubMed PMID:31112094. .

  4. Orzabal, MR, Lunde-Young, ER, Ramirez, JI, Naik, VD, Hillhouse, A, Konganti, K et al.. Gestational binge alcohol-induced alterations in maternal uterine artery transcriptome. Reprod. Toxicol. 2019;87 :42-49.
    doi: 10.1016/j.reprotox.2019.05.053. PubMed PMID:31078653. PubMed Central PMC6628922.

  5. Lewis, L, Borowa-Mazgaj, B, de Conti, A, Chappell, GA, Luo, YS, Bodnar, W et al.. Population-Based Analysis of DNA Damage and Epigenetic Effects of 1,3-Butadiene in the Mouse. Chem. Res. Toxicol. 2019;32 (5):887-898.
    doi: 10.1021/acs.chemrestox.9b00035. PubMed PMID:30990016. .

  6. Batool, M, Hillhouse, AE, Ionov, Y, Kochan, KJ, Mohebbi, F, Stoica, G et al.. New Zealand White Rabbits Effectively Clear Borrelia burgdorferi B31 despite the Bacterium's Functional vlsE Antigenic Variation System. Infect. Immun. 2019;87 (7):.
    doi: 10.1128/IAI.00164-19. PubMed PMID:30988058. PubMed Central PMC6589054.

  7. Perry, A, Lynch, RM, Rusyn, I, Threadgill, DW. Long-Term Combinatorial Exposure to Trichloroethylene and Inorganic Arsenic in Genetically Heterogeneous Mice Results in Renal Tubular Damage and Cancer-Associated Molecular Changes. G3 (Bethesda). 2019;9 (5):1729-1737.
    doi: 10.1534/g3.119.400161. PubMed PMID:30898898. PubMed Central PMC6505147.

  8. Wang, P, Wang, Y, Langley, SA, Zhou, YX, Jen, KY, Sun, Q et al.. Diverse tumour susceptibility in Collaborative Cross mice: identification of a new mouse model for human gastric tumourigenesis. Gut. 2019;68 (11):1942-1952.
    doi: 10.1136/gutjnl-2018-316691. PubMed PMID:30842212. .

  9. Orzabal, MR, Lunde-Young, ER, Ramirez, JI, Howe, SYF, Naik, VD, Lee, J et al.. Chronic exposure to e-cig aerosols during early development causes vascular dysfunction and offspring growth deficits. Transl Res. 2019;207 :70-82.
    doi: 10.1016/j.trsl.2019.01.001. PubMed PMID:30653941. PubMed Central PMC6486852.

  10. Cuomo, D, Porreca, I, Ceccarelli, M, Threadgill, DW, Barrington, WT, Petriella, A et al.. Transcriptional landscape of mouse-aged ovaries reveals a unique set of non-coding RNAs associated with physiological and environmental ovarian dysfunctions. Cell Death Discov. 2018;4 :112.
    doi: 10.1038/s41420-018-0121-y. PubMed PMID:30534420. PubMed Central PMC6281605.

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