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Ph.D., Department of Nutrition
Colorado State University
Office: 430 West Health Sciences Dr.
University of California
Davis, CA 95616
Phone: (530) 754-4838
Fax: (530) 752-5271 |
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Page Summary:
Biography
Research Interests
Research Accomplishments |
Biography
Dr. Hwang obtained his B.S. degree in Pharmacy (1967) and MPH in Public Health (1969) from Seoul National University. He earned his Ph.D. degree in Nutrition from Colorado State University (1974). From 1974 to 1977, he was a postdoctoral fellow at the Institute of Food Sciences, Cornell University. In 1978, he joined the faculty as an assistant professor in Human Nutrition at Louisiana State University. He moved to the Pennington Biomedical Research Center, Louisiana State University (1988), and was named as John S. McIlhenny Chair Professor (2000). Dr. Hwang joined the WHNRC as a research molecular biologist in December, 2002. He also has an appointment as adjunct professor in the Department of Nutrition, University of California, Davis.
Research Interests
Toll-like receptors (TLRs) and oligomerization domain containing proteins (Nods) are two major pattern recognition receptors involved in host defense against microbial pathogens. Both TLRs and Nods recognize invading pathogens, and induce innate immune responses to defend the host. However, recent evidence suggests that certain TLRs and Nods can be activated by endogenous molecules including saturated fatty acids leading to the induction of sterile inflammation. Chronic inflammation is considered as one of key pathological conditions leading to the development of many chronic diseases. Epidemiological and genetic studies have found TLRs are linked to risk of many chronic diseases. Therefore, dietary and pharmacological agents that can suppress TLR-mediated inflammation may prevent such chronic diseases.
Innate immune responses are the key for host defense against invading pathogens. However, dysregulated innate immune responses can lead to chronic inflammation which in turn can increase the risk of development and progression of chronic diseases including atherosclerosis, insulin resistance, and cancer. Dr. Hwang’s group, for the first time, demonstrated that saturated fatty acids stimulate, but polyunsaturated fatty acids (particularly n-3 PUFAs and certain plant polyphenols), inhibit TLR-receptor mediated signaling pathways and the expression of target genes. Similarly, it was shown that saturated fatty acids activate but n-3 PUFAs inhibit Nods-induced inflammatory responses. Therefore, reciprocal modulation of TLRs or Nods-mediated inflammatory responses by saturated and n-3 PUFAs will shed new light toward understanding the mechanism by which dietary fatty acids differentially modify the risk of many inflammatory chronic diseases. To validate the finding in animal disease models, Dr. Hwang is investigating whether enhanced inflammation leads to increased tumorigenic potential, and whether dietary n-3 PUFAs and plant polyphenols inhibit the tumorigenic potential as a result of suppression of TLRs or Nods-induced inflammation. Transgenic animal models in which inflammation is increased by over-expression of TLR4 in an organ specific manner will be used for these studies.
Research Accomplishments
· Proposed the conceptual framework for the mechanism by which fatty acids modulate expression of genes (Am. J. Clin. Nutr. 70:545, 1999; Ann. Rev. Nutr. 20:431, 2000).
· Dr. Hwang’s group demonstrated for the first time that NFkB transcription factor is the required component in the signaling pathways leading to the production of the inducible cyclooxygenase (COX-2) (Biochem Pharmacol 54:87, 1997; J Biol Chem 275:34035, 2000). Cyclooxygenase is the key enzyme responsible for the production of prostanoids in the body, and is over-produced in tumor and inflammatory tissues. Inhibiting this enzyme to suppress the production of prostanoids by non-steroidal anti-inflammatory drugs reduces the risk of cancer and other inflammatory diseases. This suggests that dietary factors that can inhibit the expression of cyclooxygenase should give similar beneficial effects.
· Demonstrated that saturated fatty acids stimulate, but polyunsaturated fatty acids (PUFAs), particularly n-3 PUFAs, inhibit Toll-like receptor (TLR) signaling pathways and the expression of target genes including COX-2 (J Biol. Chem 2001, J Lipid Res. 2003, J Biol. Chem 2004).
· Showed that saturated and n-3 PUFAs reciprocally modulate dendritic cell functions and T-lymphocyte activation through reciprocal modulation of TLR-signaling pathways and target gene expression.
· Demonstrated that certain plant polyphenols inhibit TLR4 and its target gene expression (Biochem Pharmacol 2006). Revealed that another pattern recognition receptor, Nods, is also reciprocally modulated by saturated and n-3 PUFAs (J. Biol. Chem 2007).
· These findings define a new paradigm for the molecular mechanism by which dietary fatty acids regulate receptor-mediated signaling pathways, target gene expression and consequent inflammatory responses. TLRs and Nods can be activated by endogenous molecules leading to the induction of sterile inflammation, which in turn can increase the risk of development and progression of chronic diseases. Therefore, these results shed new light on our understanding the mechanism by which dietary fatty acids and certain plant polyphenols differentially modify risks of many chronic diseases.
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