Thomas C Doetschman

Thomas C Doetschman

Specialist, Embryonic Stem Cell Culture
Member of the General Faculty
Primary Department
Contact
(520) 626-4901

Work Summary

I am investigating a human connective tissue disorder in mice. I am also investigating the role of gut bacteria in colon cancer risk in both a mouse model of colon cancer and in humans with colon cancer.

Research Interest

Dr. Thomas Doetschman, PhD, Biochemistry & Biophysics, University of Connecticut, has been involved in cardiovascular research for over a decade through investigations into the cardiovascular roles of the three TGFβ ligands and FGF2 ligand isoforms in genetically engineered mice. These mice have determined that TGFβ2 plays major roles in heart and vascular development and for maintenance of valvular and large vessel integrity in the adult and that both the TGFβ1 and FGF2 are involved in adult heart disease.His work has also demonstrated roles of TGFβ in cancer and immunology. He found that a major function of TGFβ1 is to inhibit autoimmunity and to establish homeostatic balance between immune regulatory and inflammatory cells. He has shown that an imbalance in the latter is critical in the tumor suppressor function of TGFβ in the colon.Dr. Doetschman has also played an important role in the development of the mouse genetic engineering field. He has been responsible for the establishment of 3 mouse genetic engineering facilities, in Cincinnati OH, Singapore and the University of Arizona’s BIO5 Institute. Keywords: "Cancer", "Microbiome", "Mouse Genetic Engineering", "Connective Tissue Disorder"

Publications

Guenard, V., Rosenbaum, T., Gwynn, L., Doetschman, T., Ratner, N., & Wood, P. (1995). Effect of transforming growth factor-beta 1 and -beta 2 on Schwann cell proliferation on neurites. GLIA, 13(4), 309-318.
Sanford, L., Kallapur, S., Ormsby, I., & Doetschman, T. (2001). Influence of genetic background on knockout mouse phenotypes.. Methods in Molecular Biology, 158, 217-225.
Tamimi, E., Ardila, D. C., Haskett, D. G., Doetschman, T., Slepian, M. J., Kellar, R. S., & Vande Geest, J. P. (2016). Biomechanical Comparison of Glutaraldehyde-Crosslinked Gelatin Fibrinogen Electrospun Scaffolds to Porcine Coronary Arteries. Journal of Biomechanical Engineering, 138(1).

Cardiovascular disease (CVD) is the leading cause of death for Americans. As coronary artery bypass graft surgery (CABG) remains a mainstay of therapy for CVD and native vein grafts are limited by issues of supply and lifespan, an effective readily available tissue-engineered vascular graft (TEVG) for use in CABG would provide drastic improvements in patient care. Biomechanical mismatch between vascular grafts and native vasculature has been shown to be the major cause of graft failure, and therefore, there is need for compliance-matched biocompatible TEVGs for clinical implantation. The current study investigates the biaxial mechanical characterization of acellular electrospun glutaraldehyde (GLUT) vapor-crosslinked gelatin/fibrinogen cylindrical constructs, using a custom-made microbiaxial optomechanical device (MOD). Constructs crosslinked for 2, 8, and 24 hrs are compared to mechanically characterized porcine left anterior descending coronary (LADC) artery. The mechanical response data were used for constitutive modeling using a modified Fung strain energy equation. The results showed that constructs crosslinked for 2 and 8 hrs exhibited circumferential and axial tangential moduli (ATM) similar to that of the LADC. Furthermore, the 8-hrs experimental group was the only one to compliance-match the LADC, with compliance values of 0.0006±0.00018 mm Hg-1 and 0.00071±0.00027 mm Hg-1, respectively. The results of this study show the feasibility of meeting mechanical specifications expected of native arteries through manipulating GLUT vapor crosslinking time. The comprehensive mechanical characterization of cylindrical biopolymer constructs in this study is an important first step to successfully develop a biopolymer compliance-matched TEVG.

Schultheis, P., Clarke, L., Meneton, P., Harline, M., Boivin, G., Stemmermann, G., Duffy, J., Doetschman, T., Miller, M., & Shull, G. (1998). Targeted disruption of the murine Na+/H+ exchanger isoform 2 gene causes reduced viability of gastric parietal cells and loss of net acid secretion. Journal of Clinical Investigation, 101(6), 1243-1253.
Engle, S., Ormsby, I., Pawlowski, S., Boivin, G., Croft, J., Balish, E., & Doetschman, T. (2002). Elimination of colon cancer in germ-free Transforming Growth Factor beta 1-deficient mice. Cancer Research, 62(22), 6362-6366.