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David W. Threadgill

David W. Threadgill

Tom and Jean McMullin Chair in Genetics

Department of Molecular and Cellular Medicine

Director, Texas A&M Institute for Genome Sciences and Society

Department of Veterinary Pathobiology

428 Reynolds Medical Building
College Station , TX
Email:
Office Phone: (979) 862-2569

Education:

  1. B.S., Zoology, Texas A&M University, 1983
  2. Ph.D., Genetics, Texas A&M University, 1989
  3. Postdoc, Genetics, Case Western Reserve University, 1990-1996

Biography:

Research Interests:

My laboratory uses the mouse as an experimental genetic model to investigate factors that contribute to inter-individual differences in health and disease. Our current 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 are developing new genetic tools to support mammalian systems genetic approaches to phenotypes with complex genetic and environmental etiologies. Cancer genetics: We are focusing on colorectal and breast 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 response: Just as individuals differ in their genetic constitution and disease susceptibility, they also differ in their responses to exogenous stimuli. We are using mouse models to investigate responses to environmental factors like the enteric flora of the gastrointestinal tract and diet and toxicants like dioxin and trichloroethane. The goal of these studies is to identify how individual responses to environmental factors leads to differential disease susceptibilities. Systems genetics resources: We are leading 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.

Recent Publications:

Phillippi J, Xie Y, Miller DR, Bell TA, Zhang Z, Lenarcic AB, Aylor DL, Krovi SH, Threadgill DW, Pardo-Manuel de Villena F, Wang W, Valdar W, Frelinger JA. 2014. Using the emerging Collaborative Cross to probe the immune system. Genes Immun. 15:38-46.

Scheving LA, Zhang X, Garcia OA, Wang RF, Stevenson MC, Threadgill DW, Russell WE. 2014. Epidermal Growth Factor Receptor Plays a Role in the Regulation of Liver and Plasma Lipid Levels in Adult Male Mice. Am J Physiol Gastrointest Liver Physiol., in press.

Desimone MC, Rathmell WK, Threadgill DW. 2013. Pleiotropic effects of the trichloroethylene-associated P81S VHL mutation on metabolism, apoptosis, and ATM-mediated DNA damage response. J Natl Cancer Inst. 105:1355-1364.


Bautz DJ, Broman KW, Threadgill DW. 2013. Identification of a novel polymorphism in X-linked sterol-4-alpha-carboxylate 3-dehydrogenase (Nsdhl) associated with reduced high-density lipoprotein cholesterol levels in I/LnJ mice. G3 3:1819-1825.


Neufert C, Becker C, Türeci Ö, Waldner MJ, Backert I, Floh K, Atreya I, Leppkes M, Jefremow A, Vieth M, Schneider-Stock R, Klinger P, Greten FR, Threadgill DW, Sahin U, Neurath MF. 2013. Tumor fibroblast-derived epiregulin promotes growth of colitis-associated neoplasms through ERK. J Clin Invest. 123:1428-1443.


Ferris MT, Aylor DL, Bottomly D, Whitmore AC, Aicher LD, Bell TA, Bradel-Tretheway B, Bryan JT, Buus RJ, Gralinski LE, Haagmans BL, McMillan L, Miller DR, Rosenzweig E, Valdar W, Wang J, Churchill GA, Threadgill DW, McWeeney SK, Katze MG, Pardo-Manuel de Villena F, Baric RS, Heise MT. 2013. Modeling host genetic regulation of influenza pathogenesis in the collaborative cross. PLoS Pathog. 9:e1003196.


Saito K, Horiuchi K, Kimura T, Mizuno S, Yoda M, Morioka H, Akiyama H, Threadgill D, Okada Y, Toyama Y, Sato K. 2013. Conditional inactivation of TNFα-converting enzyme in chondrocytes results in an elongated growth plate and shorter long bones. PLoS One 8:e54853.


Eversley CD, Yuying X, Pearsall RS, Threadgill DW. 2012. Mapping six new susceptibility to colon cancer (Scc) loci using a mouse interspecific backcross. G3 2:1577-1584.


Ardito CM, Grüner BM, Takeuchi KK, Lubeseder-Martellato C, Teichmann N, Mazur PK, Delgiorno KE, Carpenter ES, Halbrook CJ, Hall JC, Pal D, Briel T, Herner A, Trajkovic-Arsic M, Sipos B, Liou GY, Storz P, Murray NR, Threadgill DW, Sibilia M, Washington MK, Wilson CL, Schmid RM, Raines EW, Crawford HC, Siveke JT. 2012. EGF receptor is required for KRAS-induced pancreatic tumorigenesis. Cancer Cell 22:304-317.


Welsh CE, Miller DR, Manly KF, Wang J, McMillan L, Morahan G, Mott R, Iraqi FA, Threadgill DW, de Villena FP. 2012. Status and access to the Collaborative Cross population. Mamm Genome. 23706-712.


Mustafi R, Dougherty U, Shah H, Dehghan H, Gliksberg A, Wu J, Zhu H, Joseph L, Hart J, Dive C, Fichera A, Threadgill D, Bissonnette M. 2012. Both stromal cell and colonocyte epidermal growth factor receptors control HCT116 colon cancer cell growth in tumor xenografts. Carcinogenesis 33:1930-1939.


Rinella ES, Threadgill DW. 2012. Efficacy of EGFR inhibition is modulated by model, sex, genetic background and diet: implications for preclinical cancer prevention and therapy trials. PLoS One 7:e39552.


Franzke CW, Cobzaru C, Triantafyllopoulou A, Löffek S, Horiuchi K, Threadgill DW, Kurz T, van Rooijen N, Bruckner-Tuderman L, Blobel CP. 2012. Epidermal ADAM17 maintains the skin barrier by regulating EGFR ligand-dependent terminal keratinocyte differentiation. J Exp Med. 209:1105-1119.


Bottomly D, Ferris MT, Aicher LD, Rosenzweig E, Whitmore A, Aylor DL, Haagmans BL, Gralinski LE, Bradel-Tretheway BG, Bryan JT, Threadgill DW, de Villena FP, Baric RS, Katze MG, Heise M, McWeeney SK. 2012. Expression quantitative trait Loci for extreme host response to influenza a in pre-collaborative cross mice. G3 2:213-221.


Kelada SN, Aylor DL, Peck BC, Ryan JF, Tavarez U, Buus RJ, Miller DR, Chesler EJ, Threadgill DW, Churchill GA, Pardo-Manuel de Villena F, Collins FS. 2012. Genetic analysis of hematological parameters in incipient lines of the collaborative cross. G3 2:157-165.


Collaborative Cross Consortium. 2012. The genome architecture of the Collaborative Cross mouse genetic reference population. Genetics 190:389-401.


Threadgill DW, Churchill GA. 2012. Ten years of the Collaborative Cross. Genetics 190:291-294.


Rinella ES, Bankaitis ED, Threadgill DW. 2012. Dietary calcium supplementation enhances efficacy but also toxicity of EGFR inhibitor therapy for colon cancer. Cancer Biol Ther. 13:130-137.


Crowley JJ, Kim Y, Szatkiewicz JP, Pratt AL, Quackenbush CR, Adkins DE, van den Oord E, Bogue MA, Yang H, Wang W, Threadgill DW, de Villena FP, McLeod HL, Sullivan PF. 2012. Genome-wide association mapping of loci for antipsychotic-induced extrapyramidal symptoms in mice. Mamm Genome. 23:322-335.


Chen J, Chen JK, Nagai K, Plieth D, Tan M, Lee TC, Threadgill DW, Neilson EG, Harris RC. 2012. EGFR signaling promotes TGFβ-dependent renal fibrosis. J Am Soc Nephrol. 23:215-224.

Current Genetics Students:

Selene Howe

Carolina Mantilla Rojas

 

Research Interests:

Bioinformatics and Genomics:

Mouse modeling of gene-environment interactions underlying human health and diseases

Medical Genetics - Human and Animal:

Mouse modeling of gene-environment interactions underlying human health and diseases

 

Molecular, Cellular and Developmental Genetics:

Mouse modeling of gene-environment interactions underlying human health and diseases