My laboratory is interested in the pathogenesis and treatment of serious bacterial infections, sepsis, and induced secondary inflammation. Because sepsis is associated with overwhelming stimulation of the innate immune response with tissue damage, we are especially interested in the interactions of the bacterial cell wall with the host and the relationship of bacterial clearance to induced inflammation. We have an ongoing intensive project to study how and why species differ so markedly in sensitivity to inflammation and infection. We also have projects related to a variety of specific serum proteins that regulate molecular macrophage responses. One of these proteins- hemopexin- is now being developed as a therapy for patients who have degrading blood in the microenvironment of infection. Specific projects at the moment include:
1. Identification of serum proteins responsible for the marked resistance of mice to bacterial toxins
2. Study of the inflammatory gene response to trauma and sepsis in different species
3. Study of interactions of hemoglobin, heme, and bacteria on inflammation, and development of blocking drugs
4. Effect of vitamin D on immune responses in patients on dialysis
1. Warren HS. Strategies for treating sepsis. New Eng. J. Med. 1997; 336: 952-953. Editorial.
2. Ge Y, Ezzell RM, Warren HS. Localization of endotoxin in the rat intestinal epithelium. J. of Infect. Dis. 2000: 182;873-881.
3. Hellman J, Roberts JD, Tehan MM, Allaire J, Warren HS. Bacterial peptidoglycan-associated lipoprotein is released into the bloodstream in Gram-negative sepsis and causes inflammation and death in mice. J Biol Chem. 2002 Apr 19;277(16):14274-80.
4. Warren HS, Suffredini AF, Eichacker PQ, Munford RS. Risks and benefits of activated protein C treatment for severe sepsis. New Eng. J. Med. 2002; 347:1027-1030 (Sounding Board)
5. Warren HS, Matyal R, Allaire JE, Yarmush D, Loiselle P, Hellman J, Paton BG, Fink MP. Protective efficacy of CAP18106-138-IgG in sepsis J. Infect. Dis. 2003:188;1382-1393
6. Tracey KJ, Warren HS. Human genetics. An inflammatory issue Nature, 2004 May 6;429(6987):35-7.
7. Liang, MD, Bagchi, A, Warren HS, Tehan MM, Trigilio JA, Beasley-Topliffe L, Tesini B, Lazzaroni J-C, Fenton M, Hellman J. Bacterial Peptidoglycan-Associated Lipoprotein: a potent Toll-like Receptor 2 Agonist that is shed into serum and is synergistic with LPS. J. Infect Disease 2005; 191:939-948.
8. MyD88 dependent and MyD88 independent pathways in synergy, priming, and tolerance between Toll-like receptors agonists. Bagchi A, Herrup EA, Warren HS, Trigilio J, Shin HS, Valentine C, Hellman J. J. Immunol. 2007;178(2):1164-71
9. Liang X, Lin T, Sun G, Beasley-Topliffe, L, Cavaillon J-M, Warren HS. Hemopexin downregulates LPS-induced pro-inflammatory cytokines from macrophages. J Leukoc Biol. 2009 Aug;86(2):229-35.
10. Warren HS et al. Genomic Score Prognostic of Outcome in Trauma Patients. Mol Med. 2009 Jul-Aug;15(7-8):220-7.
11. Warren HS. PPARγ agonists, control of bacterial overgrowth, and inflammation. Critical Care Medicine 2009;37:773
12. Warren HS. Mouse models to study sepsis syndrome in humans. J Leukoc Biol. 2009 Aug;86(2):199-15. 13. Warren HS, Fitting C, Hoff E, Beasley-Topliffe L, Tesini B, Liang X, Adib-Conquy M, Valentine C, Helman J, Hayden D, Cavaillon JM Resilience to bacterial infection: difference between species could be due to proteins in serum. J. Infectious Disease 2010;201:223-232
14. Lin T*,Kwak Y*, Sammy F, He P, Thundivalappil S, Sun G, Chao W, Warren HS
Synergistic inflammation is induced by blood degradation products with microbial Toll-like receptor agonists and is blocked by hemopexin, J Infect Dis. 2010 Jul 9. [Epub ahead of print] PMID: 20617898.
15. Lin T, Sammy F, Yang H, Thundivalappil S, Hellman J, Tracey KJ, Warren HS. Identification of hemopexin as an anti-inflammatory factor that inhibits synergy of hemoglobin with HMGB1 in sterile and infectious inflammation. J Immunol. 2012 Aug 15;189(4):2017-22. Epub 2012 Jul 6. PMID: 22772444