David Threadgill, PhD

Research Interests

• 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 theErbbgenefamily 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.
• Specific areas of current research activity include:
• Cancer genetics We are focusing on colorectal, breast and kidney cancer to identify environmental factors and genetic polymorphisms contributing to differentialsusceptibility to the development and progression of cancer. We are also developing approaches to exploit these factors to prevent or delay cancer as well asto identify new therapies.
• Epidermal growth factor receptor (Egfr) We are using mouse models with genetically engineered or spontaneous mutations to elucidate the biological roleofEgfrand other member of theErbbgene family in vivo. These studies have lead to new insights into the role of these genes in neuronal survival andbehavior, obesity, cancer and cardiovascular disease. We are currently performing mechanistic studies to identify how theErbbgenes contribute to normaland abnormal phenotypes.
• Genetics of environmental response 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 andtoxicants like dioxin, trichloroethylene, and arsenic. The goal of these studies is to identify how individual responses to environmental factors leads to differential diseasesusceptibilities 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 theintegration of genetics into systems biological analyses at the whole animal level. These efforts are based upon the Collaborative Cross, which is a uniquerecombinant 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.

Representative Publications

• Huda MN, Salvador AC, Barrington WT, Gacasan CA, D'Souza EM, Deus Ramirez L, Threadgill DW, Bennett BJ. 2022. Gut microbiota and host genetics modulate the effect of diverse diet patterns on metabolic health. Front Nutr. Aug 18;9:896348.
• Scoggin K, Gupta J, Lynch R, Nagarajan A, Aminian M, Peterson A, Adams LG, Kirby M, Threadgill DW, Andrews-Polymenis HL. 2022. Elucidating Mechanisms of Tolerance to Salmonella Typhimurium across Long-Term Infections Using the Collaborative Cross. mBio 13(4):e0112022.
• Morgan AP, Hughes JJ, Didion JP, Jolley WJ, Campbell KJ, Threadgill DW, Bonhomme F, Searle JB, de Villena FP. 2022. Population structure and inbreeding in wild house mice (Mus musculus) at different geographic scales. Heredity 129(3):183-194.
• Wells AE, Barrington WT, Dearth S, Milind N, Carter GW, Threadgill DW, Campagna SR, Voy BH. 2022. Independent and Interactive Effects of Genetic Background and Sex on Tissue Metabolomes of Adipose, Skeletal Muscle, and Liver in Mice. Metabolites 12(4):337.
• Scoggin K, Lynch R, Gupta J, Nagarajan A, Sheffield M, Elsaadi A, Bowden C, Aminian M, Peterson A, Adams LG, Kirby M, Threadgill DW, Andrews-Polymenis HL. 2022. Genetic background influences survival of infections with Salmonella enterica serovar Typhimurium in the Collaborative Cross. PLoS Genetics 18(4):e1010075.
• Luo L, Santos A, Konganti K, Hillhouse A, Lambertz IU, Zheng Y, Gunaratna RT, Threadgill DW, Fuchs-Young RS. 2022. Overexpression of IGF-1 During Early Development Expands the Number of Mammary Stem Cells and Primes them for Transformation. Stem Cells 40(3):273-289.
• Cuomo D, Foster MJ, Threadgill DW. 2022. Systemic review of genetic and epigenetic factors underlying differential toxicity to environmental lead (Pb) exposure. Environ Sci Pollut Res Int. 29(24):35583-35598. 
• Lees-Shepard JB, Flint K, Fisher M, Omi M, Richard K, Antony M, Chen PJ, Yadav S, Threadgill DW, Maihle NJ, Dealy CN. 2022. Cross-talk between EGFR and BMP signals regulates chondrocyte maturation during endochondral ossification. Developmental Dynamics 251(1):75-94. 
• Mantilla Rojas C, McGill MP, Salvador AC, Bautz D, Threadgill DW. 2021. Epithelial-specific ERBB3 deletion results in a genetic background-dependent increase in intestinal and colon polyps that is mediated by EGFR. PLoS Genetics 17(11):e1009931. 
• Mantilla-Rojas C, Yu M, Rinella ES, Lynch RM, Perry A, Jaimes-Alvarado J, Anderson KR, Barba E, Bourgeois EJ, Konganti K, Threadgill DW. 2021. A molecular subtype of colorectal cancers initiates independently of epidermal growth factor receptor and has an accelerated growth rate mediated by IL10-dependent anergy. Oncogene 40(17):3047-3059.
• Salvador AC, Arends D, Barrington WT, Elsaadi AM, Brockmann GA, Threadgill DW. 2021. Sex-specific genetic architecture in response to American and ketogenic diets. International Journal of Obesity 45(6):1284-1297.
• Vaes N, Schonkeren SL, Rademakers G, Holland A, Koch A, Gijbels MJ, Keulers T, de Wit M, Moonen L, Van der Meer JRM, Van den Boezem E, Wolfs T, Threadgill DW, Demmers J, Fijneman R, Jimenez C, Van den Berghe P, Smits K, Rouschop K, Boesmans W, Hofstra R, Melotte V. 2021. Loss of enteric neuronal Ndrg4 promotes colorectal cancer via increased release of Nid1 and Fbln2. EMBO Reports 22(6):e51913.
• Jurgelewicz A, Dornbos P, Warren M, Nault R, Arkatkar A, Lin H, Threadgill DW, Zacharewski T, LaPres JJ. 2021. Genetics-based Approach to Identify Novel Genes Regulated by the Aryl Hydrocarbon Receptor (AHR) in Mice Liver. Toxicological Sciences 181(2):285-294. 
• Warren MR, Radulescu A, Dornbos P, Cuomo D, Zumwalt S, Bueso-Mendoza D, Nitcher M, LaPres J, Threadgill DW. 2021. Peanut butter as an alternative dose delivery method to prevent strain-dependent orogastric gavage-induced stress in mouse teratogenicity studies. J Pharmacol Toxicol Methods 107:106948.
• Zhong C, He L, Lee SY, Chang H, Zhang Y, Threadgill DW, Yuan Y, Zhou F, Celniker SE, Xia Y, Snijders AM, Mao JH. 2021. Host genetics and gut microbiota cooperatively contribute to azoxymethane-induced acute toxicity in Collaborative Cross mice. Archives of Toxicology 95:949-958.

Lab Members

Postdoctoral Research Associate

• Danila Cuomo
• Anna Salvador

Research Assistants

• Krishna Patel

Graduate Research Assistant

• Michael McGill
• Brittni Ming-Whitfield
• Ana Valesquez
• Kaitlyn Carter
• Alexandra Naron
• Casey Hughes Lago