Post-doc, Roche Pharmaceuticals, Palo Alto, CA, 2006-2009
Post-doc, University of California, San Francisco, 2005-2006
Ph.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,
Office: Copley 126
BIOL 122 Integrative Biology II
BIOL 133 Health and Immunity
BIOL 442 Immunology
BIOL 315 Infectious Disease and Public Health
HNRS 227 Dirt, Immunity, and Cancer
The 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 mice
2. 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
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
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
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.