Jill Suttles, Ph.D.

Jill Suttles, Ph.D.

 

 

Research Interests

Our research is focused on the molecular mechanisms regulating leukocyte inflammatory responses with an emphasis on the intracellular signaling pathways that control the production of inflammatory cytokines.  Our work is relevant to the pathogenesis of autoimmune disease and cancer, as well as to cellular responses to pathogens.

Research projects include:

Regulation of inflammation by Fatty Acid Binding Proteins (FABPs).FABPs act as intracellular receptors for various lipids and serve as lipid chaperones. We have found that the FABP family members, A-FABP and E-FABP regulate both inflammatory and metabolic pathways in macrophages and dendritic cells. We have also shown that E-FABP plays a role in the regulation of T lymphocyte function and mice that do not express these proteins are protected from development of autoimmune experimental encephalomyelitis, a mouse model of human multiple sclerosis. We are pursuing the hypothesis that FABPs control inflammatory and immune responses by influencing energy balance in leukocytes. These studies may help provide a better understanding of the link between metabolism, diet and immune system function.

The role AMP-activated protein kinase in leukocyte function .AMP-activated protein kinase, AMPK, is a serine/threonine kinase that regulates energy homeostasis and metabolic stress in eukaryotes.  Our lab has shown that in addition to its well-described role in the regulation of metabolic pathways, AMPK acts as a negative regulator of inflammatory signaling in macrophages and dendritic cells.  When these myeloid antigen presenting cells lack AMPK expression, they have heightened inflammatory function and an increased capacity to drive T cells to pro-inflammatory Th1 and Th17 phenotypes.  We are investigating the role of AMPK in the regulation of autoimmune inflammation as well as its influence on immune responses to tumors.

Selected Publications

Sag, D. D.Carling, R.D. Stout and J. Suttles. 2008. AMP-activated protein kinase promotes macrophage polarization to an anti-inflammatory functional phenotype. J. Immunol. 181:8633.

Li., B., J. M. Reynolds, R. D. Stout, D. A. Bernlohr and J. Suttles. 2009. Regulation of Th17 Differentiation by Epidermal Fatty Acid-Binding Protein. J. Immunol. 182:7625.

Stout, R.D., S.K. Watkins, and J. Suttles. 2009. Functional Plasticity of Macrophages: In situ re-programming of tumor-associated macrophages. J. Leukocyte Biol. 86:1105.

Suttles, J. and R.D. Stout. 2009. Macrophage CD40 signaling: a pivotal regulator of disease protection and pathogenesis. Semin. Immunol. 21:257 .

Brown, J, H. Wang, J. Suttles, D.T. Graves and M. Martin. 2011. The mammalian target of rapamycin complex 2 (mTORC2) negatively regulates the innate inflammatory response. J. Biol. Chem. 286:44295.

Carroll, K.C., B. Viollet and J. Suttles. 2013.  AMPKa1 deficiency amplifies myeloid APC activity and CD40 signaling.  J. Leuk. Biol. 94:1113.