Daniel Hwang is a Research Molecular Biologist at the Western Human Nutrition Research Center (WHNRC) and adjunct professor at the Department of Nutrition, UC Davis. Dr. Hwang obtained his B.S. degree in Pharmacy (1967) and Masters in Public Health (1969) from SeoulNationalUniversity. He earned his Ph.D. degree in nutrition from ColoradoStateUniversity(1974). From 1974 to 1977, he was a postdoctoral fellow at CornellUniversity. In 1978, he joined faculty as an assistant professor in Human Nutrition at LouisianaStateUniversity. He moved to the Pennington Biomedical Research Center, Louisiana State University(1988), and was named as John S, McIlhenny professor(2000).
Toll-like receptors(TLRs) and oligomerization domain containing proteins(Nods) are two major pattern recognition receptors(PRR) involved in host defense against microbial pathogens.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 including atherosclerosis, cancer and insulin resistance.Results from epidemiological and genetic studies linked TLRs to risk modification of many chronic diseases. Then, dietary and pharmacological agents that can suppress PRR-mediated inflammation may have preventive efficacy for such chronic diseases.
Dr. Hwang’s group, for the first time, demonstrated that saturated fatty acids stimulate but polyunsaturated fatty acids(PUFAs) particularly n-3 PUFAs, inhibit TLR signaling pathways and the expression of target genes (J Biol. Chem2001: J Lipid Res. 2003; J Biol. Chem 2004). Dr. Hwang’s subsequent work (J Immunology2005) demonstrated that saturated and n-3 PUFAs reciprocally modulate dendritic cell functions and T-lymphocyte activation as a functional consequence of the reciprocal modulation of TLR-signaling pathways and target gene expression.These findings provided a conceptual foundation that dietary fatty acids can modulate TLR4-mediated chronic inflammation and consequent risk of chronic disease. In addition, the results from Dr. Hwang’s recent studies showed that certain plant polyphenols inhibit TLR4 and its target gene expression (Biochem Pharmacol 2006). It was also revealed that another pattern recognition receptor, Nods are also reciprocally modulated by saturated and n-3 PUFAs (J. Biol. Chem 2007). Dr. Hwang’s recent studies further delineated the mechanism as to how fatty acids modulate the activation of TLR4. There is no evidence that fatty acids can directly bind TLRs. Fatty acids modulate the activation of TLR4 by regulating dimerization and recruitment of the receptor into lipid rafts in a reactive oxygen species-dependent manner (J Biol Cem 2009). These findings define a new paradigm for the molecular mechanism by which dietary fatty acids regulate TLR4-mediated signaling pathways, target gene expression and cellular (immune) responses. TLR-mediated chronic inflammation can lead to increased risk of development and progression of many chronic diseases including atherosclerosis and insulin resistance. It is now recognized that TLRs and Nods are key pattern recognition receptors that can be activated by endogenous molecules leading to sterile inflammation. Therefore, Dr. Hwang’s research interest is focused in understanding how pattern recognition receptor-mediated sterile inflammation and risk of chronic disease can be modulated by what we eat with emphasis on dietary fatty acids and phytochemicals.
·Proposed the conceptual framework for the mechanism by which fatty acids modulate receptor-mediated signaling pathways and the expression of target genes (Am. J. Clin. Nutr. 70:545, 1999; Ann. Rev. Nutr. 20:431, 2000).
·Demonstrated 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 for the first time 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. Chem2001, 2003; J Lipid Res. 2005; J Biol. Chem 2004).This finding provided a conceptual foundation thatdietary fatty acids can differentially modulate TLR-mediated inflammation and consequent chronic diseases. Studies by many other investigators have verified that dietary saturated fatty acids can activate TLR4 and lead to the induction of insulin resistance using TLR4 knockout or mutant mice.
·Demonstrated that saturated and n-3 PUFAs reciprocally modulate dendritic cell functions and T-lymphocyte activation as a functional consequence of reciprocal modulation of TLR-signaling pathways and target gene expression (J Immunology2005).
·Demonstrated that certain plant polyphenols inhibit TLR4 and its target gene expression ( Biochem Pharmacol 2006). It was also revealed that another pattern recognition receptor Nods are reciprocally modulated by saturated and n-3 PUFAs (J. Biol. Chem 2007).
·Demonstrated that saturated fatty acid lauric acid induces dimerization and recruitment of TLR4 into lipid rafts in a reactive oxygen species–dependent manner, whereas, n-3 polyunsaturated fatty acid docosahexaenoic acid inhibits the processes (J BIol Chem 2009).
These findings define a new paradigm in understanding the mechanism by which dietary fatty acids and certain plant polyphenols differentially modify risks of many chronic diseases, and implicate a new dietary strategy to delay the progression of inflammatory chronic disease resulting from dysregulated activation of pattern recognition receptors.
Hwang DH, Ogawa Y, Schaeffler A. A staturated fatty acid-induced activation of toll-like receptors is fatty acid-specific effect. Arteriosclerosis, Thrombosis, and Vascular Biology (online puplication, October 23, 2009). 2009.
Hwang DH, Fung V, Dannenberg AJ. National cancer institute workshop on chemopreventive properties of nonsteroidal anti-inflammatory drugs: Role of cox-dependent and -independent mechanisms. Neoplasia. 2002; 4: 91-7.