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Having had the good fortune to be involved in the development of the mouse genetic engineering field, Dr. Doetschman has used that technology over the past 25 years to discover the in vivo functions of the three TGFb ligands and the high and low molecular weight isoforms of FGF2. The resulting mouse strains have led to a wide-ranging set of investigations from heart, bone and palate development, to adult heart disease, autoimmune disease and colon cancer.
Dr. Doetschman's current research program focuses on modeling a human TGFβ3 SNP that leads to connective tissue disorders; and on TGFβ1 and SMAD3 function in T-cell homeostasis and colon cancer. He has established and directed genetically engineered mouse core facilities at the University of Cincinnati and the University of Arizona, was consultant for the establishment of mouse genetic engineering at the Institute of of Molecular and Cell Biology in Singapore, and was the scientific advisor for development of the NCI-Frederick’s Mouse Models of Human Cancer Repository.
Dr. Doetschman has been Co-Director of the Experimental Mouse Shared Resource since 2008.
TGFβ signaling is disrupted in up to a quarter of all human colon cancer, and inflammation often accompanies human colon cancer. We are using next generation sequencing to investigate the changes in colon mucosa/microbiome interactions that occur in a TGFβ-signaling-deficient mouse model of inflammation-associated colon cancer. Another study utilizes a nuclear green fluorescent protein indicator mouse for isolation and whole exome analysis of singe nuclei from cells at the initiating stages of mouse prostate and pancreatic cancer. This indicator mouse has applicability to a wide range of cancer models.
- Doetschman T. (2011) GI GEMs: Genetically engineered mouse models of gastrointestinal disease. Gastroenterology 140:380-385.
- Doetschman T, Sholl A, Chen HDR, Gard C, Hildeman D, Bommireddy R. (2011) Divergent effects of calcineurin Aβ on regulatory and conventional T-cell homeostasis. Clin. Immunol. 138:321-330.
- Bommireddy R, Babcock GF, Singh RR, Doetschman T. (2008) TGFbeta1 deficiency does not affect the generation and maintenance of CD4(+)CD25(+)FOXP3(+) putative T(reg) cells, but causes their numerical inadequacy and loss of regulatory function. Clin. Immunol. 127:206-213.
- Bommireddy R, Doetschman T. (2007) TGFbeta1 and T(reg) cells: alliance for tolerance. Trends Mol. Med. 13:492-501.
- Kaiser S, et al. (2007) Transcriptional recapitulation and subversion of embryonic colon development by mouse colon tumor models and human colon cancer. Genome Biol. 8:R131.
- Engle SJ, Ormsby I, Pawlowski S, Boivin GP, Croft J, Balish E, Doetschman T. (2002) Elimination of colon cancer in germ-free Transforming Growth Factor beta 1-deficient mice. Cancer Res. 62:6362-6366.
- Engle SJ, Hoying JB, Boivin GP, Ormsby I, Gartside PS, Doetschman T. (1999) Transforming growth factor beta1 suppresses nonmetastatic colon cancer at an early stage of tumorigenesis. Cancer Res. 59:3379-3386.
- Shull MM, Ormsby I, Kier AB, Pawlowski S, Diebold RJ , Yin M, Allen R, Sidman C, Proetzel G, Calvin D, Doetschman T. (1992) Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 359:693-699.
- Doetschman T, Gregg RG, Maeda N, Hooper ML, Melton DW, Thompson S, Smithies O. (1987) Targetted correction of a mutant HPRT gene in mouse embryonic stem cells. Nature 330:576-578.
Microbiome/Colon Mucosal Epithelium interactions are being investigated by next generation sequencing in collaboration with Bioinformaticist Dr. Bonnie Hurwitz, Dept of Agricultural and Biosystems Engineering.
Determination of whole expressome from single fluorescence-sorted nuclei from cells at the initiation stage of pancreatic and prostate cancer cells is being done in collaboration with Dr. David Galbraith, Therapeutic Development Program, and Dr. Ron Heimark, Cancer Biology.
Functional analysis of TGFβ signaling in mice with genetically engineered null mutations in the 3 TGFβ ligands revealed a colon tumor suppressor role for TGFβ1.
2007-Pres, Co-Director, Experimental Mouse Shared Resource (EMSR)
2006-Pres, Professor, BIO5 Institute and Dept. Cellular & Molecular Medicine, University of Arizona
2006-Pres, Founder and Director, Genetically Engineered Mouse Models (GEMM) Core Facility
1997-2002, Adjunct Professor, Institute of Molecular and Cell Biology, National University of Singapore.
1990-2006, Founder and Sr. Advisor to Gene Targeting Core Facility, U of Cincinnati
1988-2006, Assist Professor to Professor, Dept Molecular Genetics, Biochemistry & Microbiology, University of Cincinnati
1987-88, Postdoc, Gene Targeting, Dept. Genetics, University of Wisconsin
1983-86, Postdoc, Embryonic Stem Cells, Friedrich Miescher Institute, Max Planck Institute, Tubingen, Germany
1980-83, Postdoc, Muscle Development Swiss Federal Institute of Technology, Zurich, Switzerland
1980, PhD, Biochemistry & Biophysics, University of Connecticut
1968, BA, Social Studies, University of Chicago