Thomas R. (Tod) Hansen, PhD
Office: W108E ARBL Building, Foothills Campus
Dr. Hansen is the Mabel I. and Henry H. Traubert Professor and Director of the Animal Reproduction and Biotechnology Laboratory and the Equine Reproduction Laboratory. His research focuses on: 1) embryo-maternal signaling with intent to reduce early embryo mortality (i.e., miscarriage); 2) implantation of the embryo and development of the placenta to better understand and manage intrauterine growth restriction of the fetus; and 3) maternal infection with virus during pregnancy to discover how infections during pregnancy may impair the immune system and development of the fetus.
Maternal Response to Early Pregnancy. Early embryonic mortality occurs in 25-60% of pregnancies in mammals. This loss of embryos is caused by dysfunctional communication between the conceptus and the uterus during early pregnancy. Uterine and white blood cell gene expression are being examined using DNA microarray screens to clarify why and when embryos die in ruminants. We have identified several uterine and white blood cell gene products that are expressed in cows that have viable embryos, cows that have embryos destined for embryo mortality and nonpregnant cows that do not have embryos. In addition to clarifying maternal responses to the early developing conceptus, these experiments also have utility in identifying, re-synchronizing, and artificially inseminating the non-pregnant animal.
Maternal and Fetal Response to Bovine Viral Diarrhea Virus Infection during Pregnancy. Bovine viral diarrhea virus (BVDV) infections are responsible for important economic losses due to reproductive wastage, and respiratory and digestive disease in cattle. Infection of the developing fetus during early pregnancy frequently results in persistent infection (PI). PI animals are the main source of new infection in herd mates. The complex host-viral interactions resulting from persistent infection are minimally understood, particularly in the bovine host. A better understanding of the mechanisms of BVDV replication, pathogenesis, and host immune responses, particularly during the establishment of persistent infection, is important for developing more efficient means of prevention, diagnosis, and treatment of cattle. These experiments test the hypothesis that BVDV infection induces differential host gene expression in maternal and fetal blood that is distinctive in persistently infected (PI) animals. The longer-term objectives are to use differentially expressed genes as blood markers for the prenatal diagnosis of PI animals and to examine the pathogenesis of BVDV infections through the study of maternal-fetal and host-viral interactions and the signaling pathways that are affected by BVDV infection.
Fetal Heart Gene Expression in Response to Maternal Undernutrition during Pregnancy. Adequate nutrient supply during early gestation is critical for fetal organogenesis. Offspring from undernourished humans and rodents have an increased incidence of obesity, diabetes, hypertension, and cardiovascular disease as adults. In general, low weight or thinness at birth is associated with increased risk of cardiovascular and metabolic disorders in later life. Preliminary experiments in sheep revealed that a global 50% nutrient restriction (protein and energy) during the first half of gestation caused compensatory growth of left and right ventricles of the fetal heart and a marked decrease in fetal weight by day 78 of gestation. Hypertrophy of fetal left ventricle is associated with differentially expressed genes. We are studying how these differentially expressed genes function during fetal development to regulate compensatory growth as well as remodeling of the heart, which leads to adverse cardiac function in later life.
Weiner CM, Smirnova NP, Webb BT, Van Campen H, Hansen TR. 2012. Interferon stimulated genes, CXCR4 and immune cell responses in peripheral blood mononuclear cells infected with bovine viral diarrhea virus. Res Vet Sci.
Webb BT, Norrdin RW, Smirnova NP, Van Campen H, Weiner CM, Antoniazzi AQ, Bielefeldt-Ohmann H, Hansen TR. 2012. Bovine viral diarrhea virus cyclically impairs long bone trabecular modeling in experimental persistently infected fetuses. Vet Pathol.
Pickett BW and Colleagues. 2012. Sex, science and survival in academe: A history of the Animal Reproduction and Biotechnology Laboratory. Colorado State University, Animal Reproduction and Biotechnology Laboratory 181 pages.
Bielefeldt-Ohmann H, Smirnova NP, Tolnay AE, Webb BT, Antoniazzi AQ, van Campen H, Hansen TR. 2012. Neuro-invasion by a 'Trojan Horse' strategy and vasculopathy during intrauterine flavivirus infection. Int J Exp Pathol 93:24-33.
Ashley RL, Antoniazzi AQ, Anthony RV, Hansen TR. 2011. The chemokine receptor CXCR4 and its ligand CXCL12 are activated during implantation and placentation in sheep. Reprod Biol Endocrinol 9:148.
Hansen TR, Smirnova NP, Van Campen H, Shoemaker ML, Ptitsyn AA, Bielefeldt-Ohmann H. 2010. Maternal and fetal response to fetal persistent infection with bovine viral diarrhea virus. Am J Reprod Immunol 64:295-306.
Hansen TR, Henkes LK, Ashley RL, Bott RC, Antoniazzi AQ, Han H. 2010. Endocrine actions of interferon-tau in ruminants. Soc Reprod Fertil Suppl 67:325-340.
Bott RC, Ashley RL, Henkes LE, Antoniazzi AQ, Bruemmer JE, Niswender GD, Bazer FW, Spencer TE, Smirnova NP, Anthony RV, Hansen TR. 2010. Uterine vein infusion of interferon tau (IFNT) extends luteal life span in ewes. Biol Reprod 82:725-735.
Ashley RL, Henkes LE, Bouma GJ, Pru JK, Hansen TR. 2010. Deletion of the Isg15 gene results in up-regulation of decidual cell survival genes and down-regulation of adhesion genes: implication for regulation by IL-1beta. Endocrinology 151:4527-4536.
Arvisais E, Hou X, Wyatt TA, Shirasuna K, Bollwein H, Miyamoto A, Hansen TR, Rueda BR, Davis JS. 2010. Prostaglandin F2alpha represses IGF-I-stimulated IRS1/phosphatidylinositol-3-kinase/AKT signaling in the corpus luteum: role of ERK and P70 ribosomal S6 kinase. Mol Endocrinol 24:632-643.
Sorensen CM, Rempel LA, Nelson SR, Francis BR, Perry DJ, Lewis RV, Haas AL, Hansen TR. 2007. The hinge region between two ubiquitin-like domains destabilizes recombinant ISG15 in solution. Biochemistry 46:772-780.
Rempel LA, Austin KJ, Ritchie KJ, Yan M, Shen M, Zhang DE, Henkes LE, Hansen TR. 2007. Ubp43 gene expression is required for normal Isg15 expression and fetal development. Reprod Biol Endocrinol 5:13.
Oliveira JR, Henkes LE, Purcell SH, Smirnova NP, Ashley RL, Anthony RV, Hansen TR. 2007. Expression of ISGs in extrauterine tissues during early pregnancy in sheep is the consequence of endocrine release of IFN-tau from the uterine vein. Endocrinology, Provisionally Accepted.
Kashiwagi A, Digirolamo CM, Kanda Y, Niikura Y, Esmon CT, Hansen TR, Shioda T, Pru JK. 2007. The postimplantation embryo differentially regulates endometrial gene expression and decidualization. Endocrinology 148:4173-4184.
Kaneko-Tarui T, Zhang L, Austin KJ, Henkes LE, Johnson J, Hansen TR, Pru JK. 2007. Maternal and embryonic control of uterine sphingolipid-metabolizing enzymes during murine embryo implantation. Biol Reprod, In Press.
Gifford CA, Racicot K, Clark DS, Austin KJ, Hansen TR, Lucy MC, Davies CJ, Ott TL. 2007. Regulation of interferon-stimulated genes in peripheral blood leukocytes in pregnant and bred, nonpregnant dairy cows. J Dairy Sci 90:274-280.
Hansen TR, Pru JK, Han H, Rempel LA, Austin KJ. 2006. Failure of uterine-conceptus interactions in cattle. J Reprod Devel 52:S111-S120.
Han H, Austin KJ, Rempel LA, Hansen TR. 2006. Low blood ISG15 mRNA and progesterone levels are predictive of non-pregnant dairy cows. J Endocrinol 191:505-512.
Rempel LA, Francis BR, Austin KJ, Hansen TR. 2005. Isolation and sequence of an interferon-tau-inducible, pregnancy- and bovine interferon-stimulated gene product 15 (ISG15)-specific, bovine ubiquitin-activating E1-like (UBE1L) enzyme. Biol Reprod 72:365-372.
Han HC, Austin KJ, Nathanielsz PW, Ford SP, Nijland MJ, Hansen TR. 2004. Maternal nutrient restriction alters gene expression in the ovine fetal heart. J Physiol 558:111-121.
Guzeloglu A, Binelli M, Badinga L, Hansen TR, Thatcher WW. 2004. Inhibition of phorbol ester-induced PGF2alpha secretion by IFN-tau is not through regulation of protein kinase C. Prostaglandins Other Lipid Mediat 74:87-99.
Austin KJ, Carr AL, Pru JK, Hearne CE, George EL, Belden EL, Hansen TR. 2004. Localization of ISG15 and conjugated proteins in bovine endometrium using immunohistochemistry and electron microscopy. Endocrinology 145:967-975.
Vonnahme KA, Hess BW, Hansen TR, McCormick RJ, Rule DC, Moss GE, Murdoch WJ, Nijland MJ, Skinner DC, Nathanielsz PW, Ford SP. 2003. Maternal undernutrition from early- to mid-gestation leads to growth retardation, cardiac ventricular hypertrophy, and increased liver weight in the fetal sheep. Biol Reprod 69:133-140.
McDonnel AC, Van Kirk EA, Austin KJ, Hansen TR, Belden EL, Murdoch WJ. 2003. Expression of CA-125 by progestational bovine endometrium: prospective regulation and function. Reproduction 126:615-620.
Hicks BA, Etter SJ, Carnahan KG, Joyce MM, Assiri AA, Carling SJ, Kodali K, Johnson GA, Hansen TR, Mirando MA, Woods GL, Vanderwall DK, Ott TL. 2003. Expression of the uterine Mx protein in cyclic and pregnant cows, gilts, and mares. J Anim Sci 81:1552-1561.
Austin KJ, Bany BM, Belden EL, Rempel LA, Cross JC, Hansen TR. 2003. Interferon-stimulated gene-15 (Isg15) expression is up-regulated in the mouse uterus in response to the implanting conceptus. Endocrinology 144:3107-3113.
Johnson GA, Joyce MM, Yankey SJ, Hansen TR, Ott TL. 2002. The Interferon Stimulated Genes (ISG) 17 and Mx have different temporal and spatial expression in the ovine uterus suggesting more complex regulation of the Mx gene. J Endocrinol 174:R7-R11.
Zimmerman SD, Thomas DP, Velleman SG, Li X, Hansen TR, McCormick RJ. 2001. Time course of collagen and decorin changes in rat cardiac and skeletal muscle post-MI. Am J Physiol Heart Circ Physiol 281:H1816-1822.
Thatcher WW, Guzeloglu A, Mattos R, Binelli M, Hansen TR, Pru JK. 2001. Uterine-conceptus interactions and reproductive failure in cattle. Theriogenology 56:1435-1450.
Pru JK, Rueda BR, Austin KJ, Thatcher WW, Guzeloglu A, Hansen TR. 2001. Interferon-tau suppresses prostaglandin F2alpha secretion independently of the mitogen-activated protein kinase and nuclear factor kappa B pathways. Biol Reprod 64:965-973.
Pru JK, Austin KJ, Haas AL, Hansen TR. 2001. Pregnancy and interferon-tau upregulate gene expression of members of the 1-8 family in the bovine uterus. Biol Reprod 65:1471-1480.
Binelli M, Subramaniam P, Diaz T, Johnson GA, Hansen TR, Badinga L, Thatcher WW. 2001. Bovine interferon-tau stimulates the Janus kinase-signal transducer and activator of transcription pathway in bovine endometrial epithelial cells. Biol Reprod 64:654-665.
Thomas DP, Zimmerman SD, Hansen TR, Martin DT, McCormick RJ. 2000. Collagen gene expression in rat left ventricle: interactive effect of age and exercise training. J Appl Physiol 89:1462-1468.
Pru JK, Austin KJ, Perry DJ, Nighswonger AM, Hansen TR. 2000. Production, purification, and carboxy-terminal sequencing of bioactive recombinant bovine interferon-stimulated gene product 17. Biol Reprod 63:619-628.
Nighswonger AM, Austin KJ, Ealy AD, Han CS, Hansen TR. 2000. Rapid communication: the ovine cDNA encoding interferon-stimulated gene product 17 (ISG17). J Anim Sci 78:1393-1394.
Binelli M, Guzeloglu A, Badinga L, Arnold DR, Sirois J, Hansen TR, Thatcher WW. 2000. Interferon-tau modulates phorbol ester-induced production of prostaglandin and expression of cyclooxygenase-2 and phospholipase-A(2) from bovine endometrial cells. Biol Reprod 63:417-424.
Perry DJ, Austin KJ, Hansen TR. 1999. Cloning of interferon-stimulated gene 17: the promoter and nuclear proteins that regulate transcription. Mol Endocrinol 13:1197-1206.
Johnson GA, Spencer TE, Hansen TR, Austin KJ, Burghardt RC, Bazer FW. 1999. Expression of the interferon tau inducible ubiquitin cross-reactive protein in the ovine uterus. Biol Reprod 61:312-318.
Johnson GA, Austin KJ, Collins AM, Murdoch WJ, Hansen TR. 1999. Endometrial ISG17 mRNA and a related mRNA are induced by interferon-tau and localized to glandular epithelial and stromal cells from pregnant cows. Endocrine 10:243-252.
Hansen TR, Austin KJ, Perry DJ, Pru JK, Teixeira MG, Johnson GA. 1999. Mechanism of action of interferon-tau in the uterus during early pregnancy. J Reprod Fertil, Suppl 54:329-339.
Austin KJ, King CP, Vierk JE, Sasser RG, Hansen TR. 1999. Pregnancy-specific protein B induces release of an alpha chemokine in bovine endometrium. Endocrinology 140:542-545.