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Thomas Hansen

 

Office: W108E ARBL Building
Foothills Campus
Colorado State University
Fort Collins, Colo. 80523
Phone: 970-491-5621
Fax: 970-491-3557
Email: Thomas.Hansen@ColoState.edu

Thomas R. (Tod) Hansen, PhD

Director, Animal Reproduction and Biotechnology Laboratory
Traubert Professor, Department of Biomedical Sciences

Education


PhD, Texas A&M University
MS, Texas A&M University
BS, Colorado State University

Biography


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 current research focuses on: 1) embryo-maternal signaling with intent to reduce early embryo mortality (i.e., miscarriage); and 2) negative consequences of maternal infection with virus during pregnancy to discover how viral infections impair the fetal immune system and development.

Research Interests


Mechanisms of early establishment of pregnancy in the cow. A constraint to beef and dairy industries is the 30% incidence of early embryo mortality. It is conservatively estimated that beef and dairy industries lose $600 million per year because of lower weaning weights and loss in milk production due to early death of the developing embryo. Early abortion of the embryo is a serious economic loss and is caused by a dysfunctional communication between the mother and the embryo. The primary focus of the research is determining function of pregnancy-associated proteins during maternal recognition and establishment of early pregnancy. A secondary benefit of the research is delineating blood markers for a viable day 18 embryo. Knowledge of which maternal genes and function of corresponding proteins that are up-regulated in response to the embryo should lead to biotechnologies that are designed to control reproductive efficiency and, thus, improve overall reproductive management. For example, study of blood profiles of pregnancy-associated proteins is hypothesized to provide a better understanding of why and when embryos die. Likewise, knowledge of embryo-maternal interactions can be used to determine pregnancy status and facilitate more efficient estrous synchronization and re-breeding. The objectives of these experiments are to determine complete nucleotide and inferred amino acid sequence, generate recombinant protein and anti-recombinant protein antibodies, examine temporal expression of mRNAs and proteins in the uterus and blood during early pregnancy and in bovine endometrial cells treated with IFNT, and to determine function of these proteins in mediating establishment and maintenance of pregnancy in ruminants. We are currently clarifying mechanisms within the CL that are induced by pregnancy and that mediate steroidogenic and anti-luteolytic responses. Other secondary benefits and longer-term goals are to develop maternal markers for early establishment of bovine pregnancy and develop more accurate predictors of fertility in beef and dairy cows. This research has been funded through private-industry support as well as the NIH-NICHD, USDA-AFRI and Agricultural Experiment Station Funds (W112-W3112).

 
Maternal and Fetal Genetic Response to Bovine Viral Diarrhea Virus Infection. Fetal infection with noncytopathic BVDV during early gestation results in persistent infection (PI) with chronic viremia and life-long viral shedding, ensuring virus perpetuation in the population. Worldwide it infects >80% of the cattle population. The United States alone suffers losses of more than $400 million per year, designating BVDV as the costliest bovine viral disease in the country. The hypothesis for these experiments is that fetal PI alters maternal immune function, compromises fetal growth and immune responses, and results in expression of maternal blood biomarkers that can be used to identify cows carrying PI fetuses.  We have described that PI fetuses cause prolonged down-regulation of a chemokine receptor 4 (CXCR4) and associated signal transduction in maternal blood immune cells. Also, the adverse effects of PI on the fetus may be mediated by chronic exposure to the growth suppressive effects of type I interferon (IFN-I), and a deficiency in the development of lymphoid tissues. We also have described maternal serum and blood immune cell genes and proteins that were differentially expressed in pregnant heifers carrying PI fetuses. These ongoing experiments will extensively examine innate and adaptive immune responses to fetal BVDV PI using an in vivo model.  Understanding which immune responses are defective in PI fetuses is essential to the development of preventative strategies by better managing the outcome of infection or through selection of BVDV-resistant cattle. These studies provide new insights into maternal and fetal responses to infection with BVDV, which is a high priority disease because of its devastating economic impact on U.S. animal agriculture. Research has been funded through internal sources and/or the USDA-AFRI program since 2004.
 
Maternal infection with H1N1 flu virus and pregnancy outcomes. Maternal infection with flu programs placental gene expression and development of the fetal immune system with negative postnatal consequences. Epidemiologic studies of the health of people born to women following influenza A virus pandemics indicate a life-long effect of maternal influenza A viral infection on the health of the child.  The link between maternal influenza infections with pre-term birth, low birth weight, congenital defects of the heart, cardiovascular disease as adults, and neurologic/behavioral abnormalities such as schizophrenia is well-established; whereas, the effects on the developing fetal immune system, postnatal immune functions and the health of the individual as an adult have yet to be explored. In this project, we are using a pregnant mouse influenza A virus infection model to test the hypothesis that maternal infection alters placental and fetal gene expression such that offspring are immunocompromised. Potential biomarkers may be identified in compromised mouse pregnancies that can be applied to diagnose or predict human placental and neonatal immune health. The long-term goal of this project is to determine the impact of maternal infections on placental and fetal immune system programming, the postnatal immune response and the discovery of placental biomarkers for immune dysfunction. This project is submitted as a multi-PI NIH R01 grant proposal in collaboration with Yale Medical School. 

 

Representative Publications


For a complete list of publications, please visit: TR Hansen PubMed

Fetal Hepatic Response to Bovine Viral Diarrhea Virus Infection in Utero. Morarie-Kane SE, Smirnova NP, Hansen TR, Mediger J, Braun L, Chase C.Pathogens. 2018 Jun 6;7(2). pii: E54. doi: 10.3390/pathogens7020054.PMID:29882795
 
Functional roles of ornithine decarboxylase and arginine decarboxylase during the peri-implantation period of pregnancy in sheep.Lenis YY, Johnson GA, Wang X, Tang WW, Dunlap KA, Satterfield MC, Wu G, Hansen TR, Bazer FW. J Anim Sci Biotechnol. 2018 Jan 24;9:10. doi: 10.1186/s40104-017-0225-x. eCollection 2018.PMID:29410783
 
Pregnancy-induced changes in metabolome and proteome in ovine uterine flushings. Romero JJ, Liebig BE, Broeckling CD, Prenni JE, Hansen TR. Biol Reprod. 2017 Aug 1;97(2):273-287. doi:
 
Gordon Niswender, Ph.D., 1940-2017.  Nett T, Hansen TR. Biol Reprod. 2017 Aug 1;97(2):179-181. doi: 10.1093/biolre/iox073. PMID: 29044432
 
Paracrine and endocrine actions of interferon tau (IFNT). Hansen TR, Sinedino LDP, Spencer TE. Reproduction. 2017 Nov;154(5):F45-F59. doi: 10.1530/REP-17-0315. Review. PMID:28982937
 
Temporal Release, Paracrine and Endocrine Actions of Ovine Conceptus-Derived Interferon-Tau During Early Pregnancy. Romero JJ, Antoniazzi AQ, Nett TM, Ashley RL, Webb BT, Smirnova NP, Bott RC, Bruemmer JE, Bazer FW, Anthony RV, Hansen TR. Biol Reprod. 2015 Dec;93(6):146. doi: 10.1095/biolreprod.115.132860. Epub 2015 Nov 11. PMID:26559679
 
Implantation and Establishment of Pregnancy in Ruminants. Spencer TE, Hansen TR. Adv Anat Embryol Cell Biol. 2015;216:105-35. doi: 10.1007/978-3-319-15856-3_7. Review. PMID:26450497
 
Innate and adaptive immune responses to in utero infection with bovine viral diarrhea virus.Hansen TR, Smirnova NP, Webb BT, Bielefeldt-Ohmann H, Sacco RE, Van Campen H. Anim Health Res Rev. 2015 Jun;16(1):15-26. doi: 10.1017/S1466252315000122. PMID:26050568
 
Functional roles of arginine during the peri-implantation period of pregnancy. III. Arginine stimulates proliferation and interferon tau production by ovine trophectoderm cells via nitric oxide and polyamine-TSC2-MTOR signaling pathways.Wang X, Burghardt RC, Romero JJ, Hansen TR, Wu G, Bazer FW. Biol Reprod. 2015 Mar;92(3):75. doi: 10.1095/biolreprod.114.125989. Epub 2015 Feb 4. PMID: 25653279
 
Embryo mortality in Isg15-/- mice is exacerbated by environmental stress. Henkes LE, Pru JK, Ashley RL, Anthony RV, Veeramachaneni DN, Gates KC, Hansen TR. Biol Reprod. 2015 Feb;92(2):36. doi: 10.1095/biolreprod.114.122002. Epub 2014 Dec 10. PMID:25505199
 
Functional role of arginine during the peri-implantation period of pregnancy. II. Consequences of loss of function of nitric oxide synthase NOS3 mRNA in ovine conceptus trophectoderm. Wang X, Frank JW, Xu J, Dunlap KA, Satterfield MC, Burghardt RC, Romero JJ, Hansen TR, Wu G, Bazer FW. Biol Reprod. 2014 Sep;91(3):59. doi: 10.1095/biolreprod.114.121202. Epub 2014 Jul 24. PMID:25061098
 
ISGylation: a conserved pathway in mammalian pregnancy. Hansen TR, Pru JK. Adv Exp Med Biol. 2014;759:13-31. doi: 10.1007/978-1-4939-0817-2_2. Review. PMID:25030758
 
Functional role of arginine during the peri-implantation period of pregnancy. I. Consequences of loss of function of arginine transporter SLC7A1 mRNA in ovine conceptus trophectoderm. Wang X, Frank JW, Little DR, Dunlap KA, Satterfield MC, Burghardt RC, Hansen TR, Wu G, Bazer FW. FASEB J. 2014 Jul;28(7):2852-63. doi: 10.1096/fj.13-248757. Epub 2014 Mar 13. PMID: 24627544
 
Induction of interferon-gamma and downstream pathways during establishment of fetal persistent infection with bovine viral diarrhea virus. Smirnova NP, Webb BT, McGill JL, Schaut RG, Bielefeldt-Ohmann H, Van Campen H, Sacco RE, Hansen TR. Virus Res. 2014 Apr;183:95-106. doi: 10.1016/j.virusres.2014.02.002. Epub 2014 Feb 12. PMID: 24530541