Bing Li, Ph.D.

Bing Li, Ph.D.

Lab Staff:

Research Associate: Yuwen Zhang, Ph.D.

Research Technologist: Yanwen Sun

 

Postdoctoral fellows:

Enyu Rao, Ph.D.

Jiaqing Hao, Ph.D.

Jun Zeng, Ph.D

 

Research Interest

The main focus in my laboratory is to understand the role of fatty acid binding proteins (FABPs) in autoimmune diseases and cancer development. FABPs constitute a family of small, highly homologous intracellular lipid chaperones that have been recognized as central regulators of both metabolic and inflammatory pathways. We have shown that adipose FABP (A-FABP) and epidermal FABP (E-FABP) play important roles in many animal disease models, such as experimental autoimmune encephalomyelitis (EAE) model and different tumor models. However, the exact mechanisms underlying these observations remain to be determined. Currently, research in my laboratory strives to understand how FABPs regulate cellular metabolism and intracellular signal transduction pathways in leukocytes, to determine the mechanisms by which FABPs link metabolism and complex diseases, and to identify specific inhibitors of FABPs for potential drug discovery.

Carcinogenesis is a multistep complex process that depends on the crosstalk between cancer cell intrinsic factors and extrinsic immunosurveillance effects. Obesity has been established as a risk factor for cancer incidence and cancer mortality. It is likely that obesity may contribute to cancer development either through promotion of cancer cell intrinsic transformation or through subversion of the extrinsic host immune system. Our preliminary studies have demonstrated that crosstalk of tumor cells and tumor infiltrating macrophages can significantly stimulate the cytoplasmic expression of A-FABP in macrophages, which switches the phenotype of macrophages to pro-tumor development. Strikingly, a strain of mice that lacks A-FABP has been found to be protected from breast cancer development. While FABPs are traditionally recognized as cytoplasmic lipid chaperones enabling lipid distribution and coordinating their responses inside cells, we have found that obesity can significantly upregulate A-FABP expression in both macrophages and adipocytes. More importantly, tumor associated adipocytes can secrete a large amount of A-FABP into circulation in response to exposure to tumors, which may serve as a plasma biomarker for cancer early diagnosis. Therefore, our studies suggest that A-FABP exerts its effects through both local (cytoplasmic) and systemic (circulating) actions. A-FABP may promote carcinogenesis and tumor development by targeting both cancer cells and immune cells and offers a new therapeutic target for cancer treatment. In this manner, A-FABP may represent a new link between obesity and cancer.

We have also explored the role of FABPs in inflammatory autoimmune diseases. For our studies in EAE, a mouse model of human multiple sclerosis, we have demonstrated that E-FABP-deficient mice are protected from development of EAE symptoms, exhibiting reduced expression of proinflammatory cytokines in brain and spinal cord tissue as compared to wild-type mice. In addition, EFABP, but not A-FABP, expression in T cells promotes Th17 differentiation, while counterregulating development of Foxp3+ regulatory T cells. E-FABP-deficient T cells show enhanced PPARγ expression and reduced expression of RORγt and RORα. Currently, we are investigating how E-FABP deficiency regulates T cell metabolism and thereby impacting intracellular signal pathways which are necessary for T cell differentiation. Notably, evidence suggests that E-FABP deficiency may affect the activity of AMP activated kinase (AMPK) in T cells. Furthermore, AMPK deficiency in T cells suppresses Foxp3 expression, indicating the importance of E-FABP/AMPK pathway in regulating T cell functions in autoimmune diseases. Our continuing research will explore whether E-FABP regulates T cell subset differentiation via influencing both transcriptional and metabolic programs. Experiments will be performed to determine the exact role of E-FABP in T cell differentiation, to evaluate the contributions of T cell E-FABP expression versus macrophage/DC expression of E-FABP towards development and progression of autoimmune diseases, to explore the interaction of PPARγ, AMPK, mTOR and other transcription factors that regulate T cell development, and to test the impact of chemical inhibition of E-FABP in different animal models.

In summary, our studies have revealed that FABPs play essential roles in regulating cellular metabolism and immune functions. While A-FABP is more critical in regulating functions of macrophages and adipocytes in tumor development, E-FABP exhibits a unique role in T cell differentiation in inflammatory autoimmune diseases. These results will have significant implications in their potential applications.

 

Selected Publications

 

Rao E, Zhang Y, Zhu G, Hao J, Persson XM, Egilmez NK, Suttles J, Li B. Deficiency of AMPK in CD8+ T cells suppresses their anti-tumor function by inducing protein phosphatase-mediated cell death. Oncotarget, 2015, 6(10):7944-58.

Zhang YW, Li Q, Rao EY, Sun Y,   Grossmann ME,   Morris RJ, Cleary MP, Li B. Epidermal Fatty Acid Binding Protein Promotes Skin Inflammation Induced by High-Fat Diet. Immunity, 2015; 42(5):953-964

Rao E, Singh P, Li Y, Zhang Y, Chi YI, Suttles J, Li B. Targeting epidermal fatty acid binding protein for treatment of experimental autoimmune encephalomyelitis. BMC Immunol, 2015;16(1):28.

Rao E, Singh P, Zhai X, Li Y, Zhu G, Zhang Y, Hao J, Chi YI, Brown RE, Cleary MP, Li B. Inhibition of tumor growth by a newly-identified activator for epidermal fatty acid binding protein. Oncotarget, 2015 6(10):7815-27.

Zhang Y, Sun Y, Rao E, Yan F, Li Q, Zhang Y, Silverstein KA, Liu S, Sauter E, Cleary MP, Li B. Fatty acid-binding protein E-FABP restricts tumor growth by promoting IFN-β responses in tumor-associated macrophages, Cancer Research, 2014; 74:2988-98

Zhang Y, Li B.  E-FABP: regulator of immune function, Oncosceince, 2014; 6: 398-399

Zhang Y, Rao E, Li B. Shaping Immune Responses by Dysregulated adipokines in Obesity, Glob J Obes Diabetes Metab Syndr, 2014; 1(2): 106-108