• Last Name: A - F
• Last Name: G - L
• Last Name: M - R
• Last Name: S - Z

Research Interests

Efforts in our laboratory have focused on understanding the molecular basis of the "lipemia of sepsis," a facet of the acute phase response resulting from the increased production of triglyceride (TG)-rich lipoproteins by the liver. We hypothesize that chylomicrons (CM) and VLDL are components of an innate host immune response to infection and acute injury.  Specifically, CM and VLDL bind LPS forming lipoprotein-LPS complexes that are capable of regulating the hepatocellular response to inflammatory stimuli.  Current studies examine how the CM-LPS complexes are internalized and the impact of this cytoplasmic LPS on cellular function.  As such, we are a) using both in vivo and in vitro models of sepsis and acute cellular injury to delineate the mechanisms by which lipoprotein-bound LPS is internalized by and inhibits the response of various cells critical to the host innate immune response, including hepatocytes, leukocytes, NKT cells and vascular endothelial cells, and b) determining the effect of CM-bound LPS on the cellular responses to pro-inflammatory cytokines, especially TNF.  Whereas the acute inflammatory response is critical for the host to combat bacterial infections, this defensive response must be tightly regulated or it can culminate in shock, multiple organ failure and death.  Understanding how lipoproteins protect against bacterial toxins and contribute to host homeostasis is central to our understanding of the host response to infection and acute injury, and the future development of a novel therapeutic strategy based on manipulating the response of target cells to pro-inflammatory stimuli rather than blocking individual inflammatory mediators.

Selected Publications

• Kasravi FB, Welch WJ, Peters-Lideu CA, Weisgraber KH and Harris HW.  Induction of cytokine tolerance in rodent hepatocytes by chylomicron-bound LPS is LDL receptor dependent.  Shock 2003;19:157-162.
• Kasravi FB, Lee DH, Weisgraber KH and Harris HW.  Lipoprotein-bound endotoxin exerts an immunomodulatory effect on hepatocytes through the lipid A domain of LPS.  J Endotoxin Res 2005;11:19-24.
• Harris HW.  Lipoproteins are protective beyond HDL cholesterol and heart disease.  Crit Care Med. 2005 Aug;33(8):1859-60.
• Barcia AM and Harris HW.  Triglyceride-rich lipoproteins as agents of innate immunity.  Clin Infect Dis 2005;41 Suppl 7:S498-503.
• Harris HW.  Apolipoprotein E: From Alzheimer’s to Sepsis.  Crit Care Med 2005;33:2696-2697.
• Spitzer AL and Harris HW.  Statins attenuate sepsis.  Surgery 2006;139:283-287.
• Kattan OM, Kasravi FB, Elford EL, Schell MT, and Harris HW.  Apolipoprotein E mediated immune regulation in sepsis.  J Immunol 2008;181:1399-1408.

• Professor, Chief of General Surgery
• Surgery

Research Theme

• Liver, lipoproteins and innate immune responses to injury and infection

Contact Information

• Hobart.Harris@ucsfmedctr.org
• Phone: (415) 514-3891
• Fax:      (415) 476-8696

513 Parnassus Avenue, S-301                                           
• San Francisco, CA. 94143

Other UCSF Affiliations