Professor, Presidential Impact Fellow, and Texas A&M AgriLife Research Faculty Fellow
Office: 217A Cater-Mattil, College Station, Texas
Email: cdwu@tamu.edu
Phone: (979) 3217093
Education
Undergraduate Education
Hubei University of Chinese Medicine (Wuhan), China. MD, Medicine, 1992
Graduate Education
Tongji Medical University (Wuhan), China. Master of Medical Science, 1995
Beijing Medical University, China. PhD in Medical Science, 1998
Awards
Presidential Impact Fellow, TAMU, 2020
Innovative Basic Science Award, American Diabetes Association, 2017
Faculty Fellow Award, Texas A&M AgriLife Research, 2015
Junior Faculty Award, American Diabetes Association, 2010
Research Award, Minnesota Medical Foundation, 2004
Travel Award, Dept. of BMBB, the University of Minnesota, 2001
Pilot & Feasibility Research Award, Minnesota Obesity Center, 2002, 2005
Travel Award, The Center for Diabetes Research, University of Minnesota, 2001
Courses Taught
NUTR 470: Nutrition and Physiological Chemistry
NUTR 681: Nutrition Seminar
Areas of Expertise
The long-term goal of Dr. Wu’s research program is to elucidate the mechanisms underlying the pathogenesis of obesity and overnutrition-associated metabolic diseases including insulin resistance, diabetes, and fatty liver disease so that novel dietary and/or pharmacological approaches can be developed for preventing and/or treating metabolic diseases. Using molecular, cellular, and integrative approaches, the Wu lab is focused on investigating the interaction between metabolism and inflammation.
Obesity, insulin resistance, diabetes, and fatty liver disease
Research Interests and Ongoing Projects
1. Elucidating the roles of cGAMP-STING signaling in metabolic diseases (including NAFLD)
Stimulator of interferon genes (STING) is an essential modulator of innate immunity and functions to promote macrophage proinflammatory activation. The Wu Lab provided primary evidence indicating that STING expression is significantly increased in liver non-parenchymal cells (NPCs) from individuals with metabolic dysfunction-associated steatotic liver disease (MASLD, formally non-alcoholic fatty liver disease) relative to that in livers from individuals without MASLD. Using various approaches involving chimeric mice and cell co-cultures, the Wu Lab demonstrated that STING-stimulated macrophage activation promotes the development and progression of MASLD (Figure 1, in Gastroenterology, 2018 PMID: 30036520). Currently, the Wu Lab is investigating how nutrition stress triggers STING activation as it relates to macrophage activation and the pathogenesis of chronic liver diseases.
Figure 1: Role of STING in the pathogenesis of MASLD
2. Defining hepatocyte control of MASLD and obesity
As an enzyme that is expressed at the highest levels in the liver (hepatocytes), adenosine kinase catalyzes the phosphorylation of adenosine and functions to promote methionine cycle and methylation reactions. The Wu Lab provided the first line of evidence indicating that ADK amount is increased in livers of individuals with MASLD. Using multiple mouse models and cultured cells along with multi-omics, the Wu Lab demonstrated that ADK promotes excessive fat deposition in hepatocytes through decreasing fatty acid oxidation that is attributable to increased methylation of Ppara. In addition, ADK functions to promote liver inflammation in a manner involving STING activation in macrophages (Figure 2, Gastroenterology, 2023 PMID: 36181835). Currently, the Wu Lab is investigating how hepatocyte ADK responds to various nutritional stress and disease conditions to cause metabolic dysregulation with hope to develop novel and effective nutritional or pharmacological approaches for management of MASLD and associated chronic diseases.
Figure 2: Role of ADK in MASLD and obesity
3. Defining metabolic control of adipocyte functions and macrophage activation
Inducible 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, encoded by PFKFB3, is expressed at high abundance in proliferative cells including adipocytes and macrophages. The Wu Lab provided the first line of evidence indicating that the PFKFB3 in adipocytes plays a unique role in uncoupling obesity and inflammation. Upon extending their research into metabolic control of macrophage activation, the Wu Lab also demonstrated a role for PFKFB3 in regulating macrophage activation. In addition, the expression of PFKFB3 is stimulated by indole, a microbiota metabolite of tryptophan. This led to the validation of the importance of myeloid cell PFKFB3 in mediating the metabolic benefits of indole. While sharing similar functions in terms of suppressing the proinflammatory responses, the PFKFB3 in adipocytes versus macrophages examples cell-type-specific roles in metabolic control of cell functions (Figure 3). Currently, the Wu Lab is investing the role of PFKFB3 in mediating the benefits of functional foods and the associated bioactive components.
Figure 3: Differential Roles for PFKFB3 in MASLD in Cell Type-dependent Manners
Professional Summary
Publications
- Kundu, D, Kennedy, L, Zhou, T, Ekser, B, Meadows, V, Sybenga, A et al.. p16 INK4A drives non-alcoholic fatty liver disease phenotypes in high fat diet fed mice via biliary e2f1/foxo1/igf-1 signaling. Hepatology. 2023; :. doi: 10.1097/HEP.0000000000000307. PubMed PMID:36799449 .
- Wu, N, Zhou, T, Carpino, G, Baiocchi, L, Kyritsi, K, Kennedy, L et al.. Prolonged administration of a secretin receptor antagonist inhibits biliary senescence and liver fibrosis in Mdr2-/- mice. Hepatology. 2023; :. doi: 10.1097/HEP.0000000000000310. PubMed PMID:36799446 .
- Slevin, E, Koyama, S, Harrison, K, Wan, Y, Klaunig, JE, Wu, C et al.. Dysbiosis in gastrointestinal pathophysiology: Role of the gut microbiome in Gulf War Illness. J Cell Mol Med. 2023; :. doi: 10.1111/jcmm.17631. PubMed PMID:36716094 .