Education: Post-doc, Roche Pharmaceuticals, Palo Alto, CA, 2006-2009Post-doc, University of California, San Francisco, 2005-2006Ph.D., Human Medical Genetics Program and Division of Clinical Immunology, University of Colorado Health Sciences Center; Denver, CO, 2005 B.S., Magna Cum Laude, Department of Biology, Creighton University, Omaha, NE, 2000
Office: Copley 126
CoursesBIOL 122 Integrative Biology IIBIOL 133 Health and ImmunityBIOL 442 ImmunologyBIOL 315 Infectious Disease and Public HealthHNRS 227 Dirt, Immunity, and CancerResearch InterestsThe Gubbels Bupp lab is focused on studying genetic factors that govern declining immunity in aged mice. Advanced age is associated with increased susceptibility to and mortality from infectious diseases, especially influenza and pneumonia. Unfortunately, vaccination responses in the elderly are also diminished. A better understanding of the mechanisms underlying age-related deterioration of T cell immunity could inform therapies that enhance general immune function and vaccination effectiveness in this vulnerable population, since T cells are the immune component that appears to be most sensitive to the ageing process. We have recently identified the forkhead transcription factor, FoxO1, as a major regulator of T cell homeostasis. A FoxO1 homolog, DAF-16, promotes longevity in C. elegans presumably by conferring protection from reactive oxygen species. DAF-16 has also been shown to be essential for the enhanced longevity imparted by calorie restriction, a dieting regimen in which calorie consumption is reduced by 20%. Calorie restriction also appears to delay age-related decline of T cell immunity, at least in non-human primates. Together these observations suggest the intriguing possibility that in mammals, FoxO1 may be involved in retarding age-related deterioration of T cell immunity. Therefore, we aim to test the hypothesis that: FoxO1 acts as a rheostat on the ageing process in T cells and is required for the T cell-specific benefits of calorie restriction by opposing damage elicited by reactive oxygen species. These studies will provide important clues regarding the role of this transcription factor in T cell ageing and may ultimately lead to strategies to protect ageing individuals from infectious disease.
In particular, studies in the Gubbels Bupp lab will seek to:
1. Assess the impact of FoxO1 deficiency on age-associated diminishment of the peripheral naïve T cell population size and functionality in mice2. Determine the importance of FoxO1 to enhanced T cell immunity imparted by calorie restriction in ageing mice
Rao, R.R., Li, Q., Gubbels Bupp, M.R., and Shrikant, P.A. 2011. An essential role for transcription factor FoxO1 in mTORC1 mediated effector and memory CD8+ T cell differentiation. (Under review at Immunity)Jørgensen,T.N., Alfaro, J., Enriquez, H.L., Loo,W.M., Atencio,S., Gubbels Bupp, M.R., Mailloux, C.M., Metzger,T., Flannery, S., Ihekweazu, C., Rozzo, S.J., Kotzin,B.L., Rosemblatt,M., Bono, M.R., and Erickson, L.D. 2010. Development of murine lupus involves the combined genetic contribution of the SLAM and FcγR intervals within the Nba2 autoimmune susceptibility locus. Journal of Immunology 184:775-86.
Panchanathan, R., Shen, H., Hong X., Gubbels Bupp, M., Gould, K., and Choubey, D. 2009. Female and male sex hormones differentially regulate expression of Ifi202, an interferon-inducible lupus susceptibility gene within the Nba2 interval. Journal of Immunology 183:7031-8.
Gubbels Bupp, M.R., Edwards, B., Guo, C., Wei, D., Chen, G., Wong, B., Masteller, E., and Peng, S.L. 2009. T cells require Foxo1 to populate the peripheral lymphoid organs. European Journal of Immunology 39:2991-2999.
Gubbels Bupp, M.R., Jørgensen, T.N., and Kotzin, B.L. 2008. Identification of candidate genes that influence sex hormone-dependent disease phenotypes in mouse lupus. Genes and Immunity 9:47-56.
Gubbels Bupp, M.R., Li, M., Pashine, P., Aud, D., and Peng, S.L. 2008. The candidate lupus susceptibility gene Ifi202a is largely dispensable for B cell function. Rheumatology 47:103-4.
Guleria, I.,* Gubbels Bupp, M.,* Dada, S., Fife, B., Tang, Q., Ansari, M., Trikudanathan, S., Vadivel, N., Fiorina, P., Khosroshahi, A., Yagita, H., Azuma, M., Atkinson, M., Bluestone, J.A., and Sayegh, M.H. 2007. Mechanisms of PDL1-mediated regulation of autoimmune diabetes. Clinical Immunology 125:16-25. *These authors contributed equally to this manuscript
Fife, B.T., Guleria, I., Gubbels Bupp, M., Eagar, T.N., Tang, Q., Bour-Jordan, H., Yagita, H., Azuma, M., Sayegh, M.H., and Bluestone, J.A. 2006. Insulin-induced remission in new-onset NOD mice is maintained by the PD-1-PD-L1 pathway. Journal of Experimental Medicine 203:2737-47.
Gubbels, M.R., Jørgensen, T.N., Metzger, T.E., Menze, K., Steele, H., Flannery, S.A., Rozzo, S.J., and Kotzin, B.L. 2005. Effects of MHC and gender on autoantibody production and lupus nephritis in Nba2 congenic mice. Journal of Immunology 175:6190-6.
Jorgensen, T.N., Gubbels, M.R., and Kotzin, B.L. 2004. New insights into disease pathogenesis from mouse lupus genetics. Current Opinion in Immunology 16:787-93.
Jorgensen, T.N., Gubbels, M.R., and Kotzin, B.L. 2003. Links between type I interferons and the genetic basis of disease in mouse lupus. Autoimmunity 36:491-502.