Immunometabolism has emerged as a new frontier in Immunology research.  Our lab is in this area examining the impact of changes in carbohydrate and fat metabolism on T cell function.  This is important because the T cell is a key immunoregulatory subset controling both the type and extent of an immune response.  We are particularly interested in modulating the proinflammatory Th17 subset and the immunosuppressive Treg subsets to improve health.  We use genetically altered animal models and dietary factors like omeg-3 fatty acids, diet induced obesity and phytochemicals to modify lipid metabolism in the T cell in order to understand the etiology of aging, obesity and cancer and ultimately develop strategies to delay the onset of these human diseases. 

Recently, we have identified a novel lipid metabolic target for regulating T cell function.  We have found that gpat-1 (glycerol-3-phosphate acyltransferase-1) can regulate the amount of Th17 and Treg cells in mice.  This is significant because gpat-1 is the initial and rate limiting step in phospholipid and triglyceride biosynthesis.  Specifically, we found that gpat-1 knockout mouse young adult T cells have an old T cell phenotype characterized by elevated proinflammatory Th17 and immunosuppressive Tregs.  The increase in inflammation combined with suppressed adaptive immunity by the Tregs provides the perfect storm for the development of some disease like prostate cancer.  Work along these lines is continuing to understand the role of phospholipid metabolism in T cel function and using the gpat-1 knockout mouse as an aged T cell model to study prostate cancer development.

We have also found that obesity in young adolescent wild type mice decreases the number of new T cells being produced by the thymus.  This is significant because T cell production by the thymus is greatest between birth and adolescence so anyting impacting T cell production in early life can impact the robustness of the immune system in later life.  Strikingly, we found that including resveratrol in the diets of the mice while they were developing obesity resulted in less weight gain and T cell production was maintain at levels similar to normal weight mice.  Resveratrol is a phytochemical known to stimulate fat breakdown and therefore may be able offset some the negative effects of high fat diets leading to obesity.  We are currently seeking funding to continues with this project. 

Selected Publications

Peer-Reviewed Papers

A. deAngulo, R. Faris, C.A. Jolly, B. Daniels and L.A. deGrafenried. 2015. Age-related Increase in IL-17 Activates Pro-inflammatory Signaling in Prostate Cells. Prostate. (in press)

R. Faris, Y.Y. Fan, A. deAngulo, L.A. deGraffenried, R.S. Chapkin and C.A. Jolly. 2014. Glycerol-3-Phosphate Acyltransferase Is Necessary for Activation of the Stimulation Induced Metabolic Switch in Murine CD4⁺ T cells. 1842(10):1475-82. PMID:25066474

L. W. Bowers, I. X.F. Maximo, A. J. Brenner, M. Beeram, S. D. Hursting, R. S. Price, R. R. Tekmal, C. A. Jolly, and L. A. deGraffenried. 2014. NSAID use reduces breast cancer recurrence in overweight and obese women: Role of prostaglandin-aromatase interactions. Cancer Res. 74(16):4446-57

A. Gulvady, R. Cabrera, H.P. Ciolino and C.A. Jolly. 2013. Resveratrol inhibits the deleterious effects of diet induced obesity on thymic function. J. Nutr. Biochem. 24(9):1625-33

A. De Angulo, D. Cavazos, R. Faris, C.A. Jolly, B. Daniel and L.A. deGraffenried. 2013. Age related alterations in T lymphocytes modulates key pathways in prostate tumorigenesis. Prostate. 73(8):855-64

A.A. Gulvady, Murphy, E.J., Ciolino, H.P., Cabrera, R.M. and Jolly, C.A. 2013. Glycerol-3-phosphate acyltransferase-1 gene ablation results in altered thymocyte lipid content and reduces thymic T cell production in mice. Lipids 48:3-12

L.W. Collison, E.J. Murphy and Jolly, C.A. 2008. Glycerol-3-phosphate Acyltransferase-1 Regulates Murine T-lymphocyte Proliferation and Cytokine Production Amer. J. Phys.: Cell Phys. 295:1543-1549

L.W. Collison and Jolly, C.A. 2006. Aging Alters Phosphorylation Dependent Increases in Mitochondrial Glyerol-3-phosphate Acyltransferase 1 Activity in T-lymphocytes. Biochim. Biophys. Acta 1761:129-139

L.W. Collison, George, C., Murphy, E.J. and Jolly, C.A. 2005. "Dietary Flaxseed and Fish Oils Increase T-lymphocyte Acyl-CoA Binding Protein Expression and Phospholipid Mass." Lipids 40:81-87.

L.W. Collison, Kannan, L., Oronato, T., Knudsen, J., Haldar, D., Knudsen, J. and Jolly, C.A. 2005. "Aging reduces glycerol-3-phosphate acyltransferase activity in activated T-lymphocytes." Biochim. Biophys. Acta. 1687(1-3):164-172.

Z. Xu, George, C. and Jolly, C.A. 2004. "CD28 activation does not down regulate cbl-b expression in aged rat T-lymphocytes." Mech. Ag. Develop. 125(9):595-602.

C.A. Jolly. 2004. "Dietary restriction and immune function." J. Ntr. 134(8):1853-1856. L. Kannan, Knudsen, J. and Jolly, C.A. 2003. "Aging and acyl-CoA binding protein alters mitochondrial glycerol-3-phosphate acyltransferase activity." Biochim. Biophys. Acta. 1631(1):12-16.

C.A. Jolly and Kannan, L. 2002. "Lysophosphatidic acid acyltransferase activity is enhanced by albumin in T-lymphocyte membranes." Lipids. 37(5):475-480.

Book Chapters

C.A. Jolly and Kannan, L. 2002. Phosphatidic acid metabolism in mammals. In LIPIDS: Glycerolipid Metabolizing Enzymes, D. Haldar and S. K. Das, eds. Research Signpost, Kerala, India, p 29-41.

C.A. Jolly and Murphy, E.J. 2003. "Role of FABP in Cellular Phospholipid Metabolism." In Mammalian Fatty Acid Binding Proteins: Structure and Roles in Cell Homeostasis, A.K. Duttaroy and D.R. Spener, eds. P. 327-342.

G. Fernandes, Lawrence, R.A. and Jolly, C.A. 2005. "Nutrition and Immunology." In Modern Nutrition in Health and Disease, Shils, Olson, Shike and Ross, eds. (submitted).

C.A. Jolly and Xu, Z. 2006. Models of Immune Function in Aging. In Handbook of Models for Human Aging, P.M. Conn, ed. p 771-780

C. A. Jolly. 2008. Omega-3 PUFA and Immunosenescence. In Handbook on Immunosenescence: Basic Understanding and Clinical Applications. Fulop, Hirokawa, Pawelec and Franceshi, eds. P 1423-1436

Invited Reviews

C. A. Jolly. 2005. "Diet Manipulation and Prevention in Aging, Cancer and Autoimmune Disease." Curr. Opin. Clin. Ntr. Met. Care. (submitted)

C. A. Jolly. 2007. Is Dietary Restriction Beneficial for Human Health, such as for Immune Function? Curr. Opin. Lipidol. 18:53-57

S.R. Shaikh, Chapkin, R.S. and Jolly, C.A. 2012. n-3 Polyunsaturated fatty acids exert immunomodulatory effects on lymphocytes by targeting plasma membrane molecular organization. Mol. Asp. Med. 33(1):46-54

2004 – BioServ Award – given for meritorious research involving experimental animals sponsored by BioServ Inc. and the American Society for Nutritional Sciences

2006-07 – Chair, Nutrition Immunology Research Interest Section, ASN

2011 – College nominee for Dad’s Association Centennial Teaching Fellowship

2013 – College of Natural Sciences Teaching Excellence Award

2009 – Member, Special Emphasis Panel Endocrinology, Metabolism, Nutrition and Reproductive Sciences Study Section, NIH

2010 - Ad hoc reviewer for the National Science and Engineering Research Canada Discovery grant program

2014 – Member, USDA Inflammation Panel, reviewed proposal from USDA Human Nutrition Research Centers

2007 – “Mechanisms of Nutrient Regulation of Immune Cell Function” (presented in a Minisymposium at Experimental Biology 2007, Washington, DC)

2007 -   “Mechanisms of Omega-3 Fatty Acid Suppression of T-lymphocyte Function” (presented at the FASEB Summer Research Conference, Tuscon, AZ)

2011 – “Omega-3 Fatty Acids and T cell Function” (presented at FASEB Summer Research Conference, Carefree, AZ)

NTR 312H -Nutrition Honors

NTR 326 - Intermediary Metabolism