Assistant Investigator, The Feinstein Institute for Medical Research
Phone: (516) 562-1112
Our research focus is to uncover the mechanisms underlying the pathogenesis of human inflammatory diseases such as sepsis.
Severe sepsis is an overwhelming systemic inflammatory response to infection, claiming approximately 225,000 victims annually in the U.S. alone. The excessive accumulation of various pro-inflammatory cytokines reflects dysregulated inflammatory responses and lead to multiple organ failures and consequently high mortality. In 1999, Dr. Haichao Wang and his collaborators discovered that a ubiquitous nucleosomal protein, HMGB1, as a critical late mediator of lethal endotoxemia (Science 1999, 285: 248-251). This seminal discovery triggered intense research interests to uncover the mechanisms of HMGB1 release from immune cells and systemic accumulation in patients suffering from severe sepsis. In addition, this report also stimulated the search for agents that are capable of attenuating circulating HMGB1 levels and thus hold therapeutic potentials.
Recently, we have discovered that several gradients of traditional herbs can block bacterial endotoxin-stimulated HMGB1 release by immune cells and protect laboratory mice against lethal sepsis. These gradients include tanshinone from Danshen (Salvia miltiorrhiza), epigallocatechin-3-gallate from Green tea (Camellia sinensis), and carbenoxolone, a derivative of a Gancao (Radix glycyrrhizae) component, glycyrrhizin (Li et al., 2007a,b, 2011; Zhang et al., 2012). Ongoing investigations are aimed at further clarification of molecular mechanisms underlying the protective effects of these agents and exploration of possible clinical testing.
Sepsis patients manifest a variety of clinical syndromes after a multi-phased progression pathogenesis. Even though HMGB1 has been well-established as a critical mediator of sepsis lethality, delineation of signaling cascades leading to HMGB1 release may have broader implications in systemic inflammatory diseases. On the other hand, identification of HMGB1 effectors may offer the potential of developing more specific therapeutic candidates.
Sepsis severely affects a significant number of populations and represents an important unmet medical need, as no effective treatments are available. We have made tremendous progress in understanding this disease in the past and will spare no effort in our research in the future. Our goal is clear: making effective treatment options available to patients as soon as possible.