Warren Laboratory: H. Shaw Warren, MD

About Us

The Warren Laboratory is interested in the pathogenesis and treatment of serious bacterial infections, sepsis, and induced secondary inflammation from any cause. 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 microbial clearance to induced inflammation. Our work spans from basic to translational to clinical studies. While new projects are starting all the time, our work has recently become more focused on two thrust areas.

SPIRIT

Species Inspired Research for Innovative Treatments (SPIRIT) is an ongoing large-scale project in the Warren Lab that aspires to better understand why species respond differently to inflammatory stimuli and infection. We believe that a better understanding of these species differences will permit advances in the translation of results in animal models to human settings and that exploration of the underlying mechanisms could explain heterogeneity of human responses and inspire novel approaches to treat human diseases. For more information about SPIRIT, please go to the SPIRIT section of our site.

Heme in Inflammation

A second major thrust area of the laboratory has been to study the role of heme in inflammation. We have learned that red blood cells release hemoglobin in numerous clinical settings, and that cell-free hemoglobin and liberated heme greatly amplify secondary inflammation. We are hopeful that a better understanding of these mechanisms may lead to novel approaches to block potentially damaging inflammation in tissues. For more information about the role of hemoglobin and heme in inflammation and our approaches to block it, please go to the Role of Heme in Inflammation section of our site, under the Research Projects tab.

Resources

• Glue Grant Information
• Harvard Medical School

Our Team

Shaw Warren, MD

Shaw Warren, MD is an Associate Professor of Pediatrics at Harvard Medical School. In addition, he holds appointments at Massachusetts General Hospital, Shriners Hospitals for Children – Boston, and Spaulding Rehabilitation Hospital. He is also an Associate Faculty member at the Wyss Institute. Dr. Warren graduated from Harvard College in 1973 and Harvard Medical School in 1978. He trained in Infectious Diseases at the Beth Israel Hospital and received further research training at the Dana Farber Cancer Center before doing post-graduate work for three years in the department of Experimental Immunotherapy at the Institute Pasteur, during which time he was supported by a Fulbright Fellowship and then a Mosely Fellowship from Harvard Medical School. He then returned to work at the Massachusetts General Hospital, where he has run a laboratory in the area of host response and inflammation for 25 years.

Dr. Warren is a Fellow of the Infectious Disease Society of America, and member of the American Society for Microbiology, the American Association for the Advancement of Science, Kunkel Society, Massachusetts Infectious Disease Society, and the Pediatric Infectious Disease Society. He has published over 110 articles, book chapters, reviews, letters and editorials relating to inflammation, immunity and infectious disease.

Tian Lin, MD, PhD

Tian Lin, MD, PhD is an Instructor of Pediatrics at Harvard Medical School. Dr. Lin also holds appointments at Massachusetts General Hospital and Shriners Hospitals for Children – Boston. She received her doctorate in medicine from Tongji Medical University, and she performed her medical residency and practiced Internal Medicine at the Second Affiliated Hospital of Guangdong Pharmaceutical University in China. In 2005, Dr. Lin received her PhD in Microbiology and Immunology from the University of North Carolina at Charlotte. After conducting postdoctoral training in the Department of Pathology at Tufts Medical School, Dr. Lin joined the Warren Lab in 2007.

Dr. Lin has a longstanding interest in host-pathogen interactions in infectious diseases. Her PhD research focused on the host immune response to Salmonella infection. At the Warren Lab, Dr. Lin and her colleagues discovered the synergistic inflammation induced by heme and hemoglobin with multiple microbial TLR agonists and HMGB1, and has been studying hemopexin, a serum protein, as a potential therapeutic reagent to control overactive immune responses in several clinical conditions. These studies were published in many peer reviewed journals and are now the basis for multiple translational research endeavors. Dr. Lin is the principle investigator of the Shriners Hospital for Children grant “Hemopexin suppresses inflammation in burn wounds.” In addition to conducting laboratory research, Dr. Lin teaches preclinical courses at Harvard Medical School.

Frank Riley, MS

Frank Riley, MS is the Laboratory Manager for the Warren Laboratory and a Project Manager for the SPIRIT Project. Mr. Riley received a Master of Science in Applied Medical Sciences from the University of Southern Maine in 2010. Mr. Riley studied the effects of serial passaging on adipose-derived mesenchymal stem cells and the role of mitochondrial health in intervertebral disc degeneration before joining the Warren Lab in 2012. Since joining the Warren Lab, amongst other topics, Mr. Riley has studied whether heme-related parameters can be used to predict patient outcome in various secondary infectious diseases such as ARDS, malaria and burns.

Learn more about research in the Infectious Diseases Division.

Our Research

Species Inspired Research for Innovative Treatments (SPIRIT)

The SPIRIT project is an ongoing large-scale project in the Warren Lab to better understand why there is such a marked difference in sensitivity of different vertebrate species to many pro-inflammatory stimuli, including bacteria and agonists of most Toll-like receptors. SPIRIT was born out of previous work that Dr. Warren conducted while on sabbatical at the Institut Pasteur in Paris in 2003.

Mice are the most commonly used animal model for the study of inflammatory diseases. However, it has become increasingly apparent that results generated in mouse models reflect human disease poorly. Mice are highly resistant to most inflammatory challenges relative to humans. For example, mice are a million-fold more resistant to a common bacterial toxin, endotoxin, than humans. In addition, certain other vertebrate species, including some primates such as baboons, also evolved high natural resistance to inflammation. These mostly ignored observations seem essential in order to appropriately extrapolate results from studies in animal models to human disease. The failure of animal models to adequately mimic human disease is a major problem for biomedical research and for drug development. As a direct effect, there are costly errors and inefficiencies in the way that research is performed, and drugs are developed. The Warren Lab is committed to understanding the reasons for the broad variation that exists across species in regard to inflammatory response.

The ultimate goal of SPIRIT is to take advantage of the innate resilience that some species such as mice have evolved to resist inflammation and to use this information to inspire novel treatment approaches for humans. Our earlier work suggests that one reason that resilient species such as mice can resist high degrees of inflammatory challenge may be that proteins in the plasma of mice re-program and down-regulate immune cells such as macrophages to resist secondary inflammatory toxicity. We are hopeful that this concept might be harnessed to transiently re-program human cells during acute inflammatory states to become resilient to pro-inflammatory stimuli. In essence, the SPIRIT program seeks to take advantage of the inherent resistance of mice and/or other resistant species to lead towards new treatment approaches for humans.

In addition to developing new treatments, SPIRIT may aid in the construction of better animal models of human inflammation. Since current mouse models do not mimic human disease very well because of the large differences in response to inflammation, knowledge on the re-programming of immune cells by mouse proteins to handle inflammation differently than humans should lead to development of more suitable mouse models. Understanding these differences would revolutionize biomedical research and drug and vaccine development. More information about this aspect of SPIRIT can be viewed in Dr. Warren’s TEDMED talk.

Specific research interests within SPIRIT include:

• Identification of serum proteins responsible for the marked resistance of mice (and other resistant species) to bacterial toxins
• Study and comparison of inflammatory gene responses to trauma and sepsis in different species.

We are exploring the inflammatory sensitivity and resistance of non-rodent species, including members of the primate order such as chimpanzees, baboons, and other primates that are more closely related to humans than mice. By studying primates that differ from humans in innate immune responses, we hope to elucidate mechanisms that might be more directly adapted for human approaches.

SPIRIT is by nature an interdisciplinary endeavor that requires cooperation from experts in several fields of study. Our research overlaps with the fields of genomics, systems biology, primatology, theoretical biology, and others. With this in mind, the Warren Lab is always excited to connect with investigators interested in potential collaboration. If you would be interested in further exploring this potential, feel free to contact Dr. Warren using the contact section of our site.

The Role of Heme in Inflammation

One early result of the SPIRIT approach is the Warren Lab’s work relating to the role of heme in inflammation. Researchers in our group (together with our collaborators at the Institut Pasteur in Paris) noted that mice respond much differently than humans to endotoxin challenge and that plasma proteins may be involved in their relative resistance. An effort to determine the responsible proteins led to the discovery of a heme-binding protein, hemopexin, which reduces the effects of heme and hemoglobin on macrophages. Although we now believe that hemopexin is not a dominant protein involved in causing the differential resistance of mice and humans to inflammation, we have learned that that extracellular heme may be important in amplifying tissue inflammation in the presence of additional inflammatory stimuli.

In patients with inflamed or necrotic tissues, it is common for microorganisms and degrading blood products to be present at the same time. In this situation, the integrity of red blood cells is lost and hemoglobin is released into the extracellular space. Hemoglobin is a metalloprotein that contains heme (a planar and hydrophobic porphyrin ring containing an iron atom, Fe2+, in the center of the ring). Heme serves as a reversible O2 binding site and redox center and its presence outside of red cell membranes leads to oxidizing injury. Extracellular hemoglobin is rapidly auto-oxidized, spontaneously releasing heme with direct tissue toxicity. We find that while hemoglobin and heme only minimally activate macrophages by themselves, both of these molecules markedly amplify the activation of macrophages when present at the same time as microbial and/or endogenous pro-inflammatory mediators. This finding may explain why the degrading red blood cell contents released after hemolysis or minor trauma or surgery only result in mild inflammation, whereas blood in tissues that is present at the same time as infection causes marked inflammation. The concept that tissue inflammation is driven or amplified by released hemoglobin and heme is a new paradigm.

Our laboratory has found that hemopexin strongly suppresses the amplified inflammatory response. Because this response is synergistic in nature, suppression of the heme component results in large decreases in pro-inflammatory cytokine production from cultured cells. We believe these findings raise the possibility that hemopexin might be helpful as a new treatment that could be used to decrease secondary inflammation in situations where there is rupture and degradation of red blood cells outside of the bloodstream in the presence of a second stimuli, such as microbes.

In order to facilitate translation to human trials it will be important to understand both the molecular mechanisms underlying the synergy and its suppression by hemopexin, as well as other heme-related parameters in relevant clinical settings. Current projects in the laboratory include:

• Efforts to further elucidate basic mechanisms underlying heme-induced inflammation
• Translational studies correlating heme parameters to outcome in multiple relevant clinical settings
• Determination of who might most benefit from hemopexin administration

Research Positions

Project Manager

The Warren Lab is currently seeking a project manager to help coordinate the SPIRIT project. This is a large scale, multi-institution project focused on understanding and taking advantage of species differences in innate immunity to develop new strategies to treat inflammation. Please send inquiries to swarren1@partners.org.

Research Technologist

The Warren Lab is currently seeking a technologist to work on technical aspects of the SPIRIT project. Please send inquiries to swarren1@partners.org.

Publications

Original Articles

Huan Yang, Haichao Wang, Yaakov A. Levine, Manoj K. Gunasekaran, Yongjun Wang, Meghan Addorisio, Shu Zhu, Wei Li, Jianhua Li, Dominique P.V. de Kleijn, Peder S. Olofsson, H. Shaw Warren, Mingzhu He, Yousef Al-Abed, Jesse Roth, Daniel J. Antoine, Sangeeta S. Chavan, Ulf Andersson, and Kevin J. Tracey. Identification of CD163 as an antiinflammatory receptor for HMGB1-haptoglobin complexes. JCI Insight. 2016; 1(7):e85375. doi:10.1172/jci.insight.85375.

Zeng MY, Cisalpino D, Varadarajan S, Hellman J, Warren HS, Cascalho M, Inohara N, Núñez G. Gut Microbiota-Induced Immunoglobulin G Controls Systemic Infection by Symbiotic Bacteria and Pathogens. Immunity. 2016; 44(3):647-58. PMID: 26944199

Abers MS, Ghebremichael MS, Timmons AK; Warren HS; Poznansky MC; Vyas JM. Critical Reappraisal of Prolonged Neutropenia as a Risk Factor for Invasive Pulmonary Aspergillosis. Open Forum Infect Dis 2016 Feb 12; 3(1). doi: ofw036. doi: 10.1093/ofid/ofw036. eCollection 2016. PMID: 27006961

Jones CN, Hoang AN, Martel JM, Dimisko L, Mikkola A, Inoue Y, Kuriyama N, Yamada M, Hamza B, Kaneki M, Warren HS, Brown DE, Irimia D. Microfluidic assay for precise measurements of mouse, rat, and human neutrophil chemotaxis in whole-blood droplets. J Leukoc Biol. 2016 Jan 27; pii: jlb.5TA0715-310RR. [Epub ahead of print]. PMID: 26819316

Lin T, Liu J, Huang F, Van Engelen TS, Thundivalappil SR, Riley FE, Super M, Watters AL, Smith A, Brinkman N, Ingber DE, Warren HS. Purified and recombinant hemopexin: protease activity and effect on neutrophil chemotaxis. Mol Med. 2016 Jan 8. doi: 10.2119/molmed.2016.00006. [Epub ahead of print]. PMID: 26772775

Elphinstone RE, Riley F, Lin T, Higgins S, Dhabangi A, Musoke C, Cserti-Gazdewich C, Regan RF, Warren HS, Kain KC. Dysregulation of the haem-haemopexin axis is associated with severe malaria in a case-control study of Ugandan children. Malar J. 2015 Dec 21;14(1):511. doi:10.1186/s12936-015-1028-1. PMID: 26691827

Bhan I, Dobens D, Tamez H, Deferio JJ, Li YC, Warren HS, Ankers E, Wenger J, Tucker JK, Trottier C, Pathan F, Kalim S, Nigwekar SU, Thadhani R. Nutritional vitamin D supplementation in dialysis: a randomized trial. Clin J Am Soc Nephrol. 2015;10(4):611-9. PMID: 25770176

Lin T, Maita D, Thundivalappil SR, Riley FE, Hambsch J, Van Marter LJ, Christou HA, Berra L, Fagan S, Christiani DC, Warren HS. Hemopexin in severe inflammation and infection: mouse models and human diseases. Crit Care. 2015 Apr 15; 19:166. doi: 10.1186/s13054-015-0885-x. PMID: 25888135

Jones CN, Moore MM, Dimisko L, Alexander A, Ibrahim A, Hassell BA, Warren HS, Tompkins RG, Fagan SP, Irimia D. Spontaneus Neutrophil Migration Patterns during sepsis after major burns. PLoS One. 2014 Dec 9; 9(12):e114509. doi: 10.1371/journal.pone.0114509. eCollection 2014. PMID:25489947

Leblanc P, Moise L, Luza C, Chantaralawan K, Lezeau L, Yuan J, Field M, Richer D, Boyle C, Martin WD, Fishman JB, Berg EA, Baker D, Zeigler B, Mais DE, Taylor W, Coleman R, Warren HS, Gelfand JA, De Groot AS, Brauns T, Poznansky MC. VaxCelerate II: Rapid Development of a Self-Assembling Vaccine for Lassa Fever. Hum Vaccin Immunother. 2014; 10(10):3022-38. PMID:25483693

Malo MS, Moaven O, Muhammad N, Biswas B, Alam SN, Economopoulos KP, Gul SS, Hamarneh SR, Malo NS, Teshager A, Mohamed MM, Tao Q, Narisawa S, Millán JL, Hohmann EL, Warren HS, Robson SC, Hodin RA. Intestinal alkaline phosphatase promotes gut bacterial growth by reducing the concentration of luminal nucleotides. Am J Physiol Gastrointest Liver Physiol. 2014; 306(10):G826-38. PMID: 24722905

Moss AK, Hamarneh SR, Mohamed MM, Ramasamy S, Yammine H, Patel P, Kaliannan K, Alam SN, Muhammad N, Moaven O, Teshager A, Malo NS, Narisawa S, Millán JL, Warren HS, Hohmann E, Malo MS, Hodin RA. Intestinal alkaline phosphatase inhibits the proinflammatory nucleotide uridine diphosphate. Am J Physiol Gastrointest Liver Physiol. 2013; 304(6):G597-604. doi: 10.1152/ajpgi.00455.2012. PMID: 23306083

JunheeSeok, H. Shaw Warren, Alex G. Cuenca, Michael N. Mindrinos, Henry V. Baker, WeihongXu, Daniel R. Richards, Grace P. McDonald-Smith, Hong Gao, Laura Hennessy, Celeste C. Finnerty, M. Cecilia López, Shari Honari, Ernest E. Moore, Joseph P. Minei, Joseph Cuschieri, Paul E. Bankey, Jeffrey L. Johnson, Jason Sperry, Avery B. Nathens, Timothy R. Billiar, Michael A. West, Marc G. Jeschke, Matthew B. Klein, Richard L. Gamelli, Nicole S. Gibran, Bernard H. Brownstein, Carol Miller-Graziano, Steve E. Calvano, Philip H. Mason, John D. Storey, J. Perren Cobb, Laurence G. Rahme, Stephen F. Lowry, Ronald V. Maier, Lyle L. Moldawer, David N. Herndon, Ronald W. Davis, Wenzhong Xiao, Ronald G. Tompkins, and the Inflammation and Host Response to Injury, Large Scale Collaborative Research Program. Gene response in mouse models poorly mimics severe human inflammatory diseases. ProcNatlAcadSci U S A. 2013; 110(9):3507-12. PMID: 23401516

Cuenca AG, Gentile LF, Lopez MC, Ungaro R, Liu H, Xiao W, Seok J, Mindrinos MN, Ang D, OzrazgatBaslanti T, Bihorac A, Efron PA, Cuschieri J, Warren HS, Tompkins RG, Maier RV, Baker HV, Moldawer LL; the Inflammation and Host Response to Injury Collaborative Research Program. Development of a Genomic Metric that can be Rapidly Used to Predict Clinical Outcome in Severely Injured Trauma Patients. Crit Care Med. 2013 May;41(5):1175-85. doi: 10.1097/CCM.0b013e318277131c. PMID: 23388514

Kaliannan K, Hamarneh SR, Economopoulos KP, NasrinAlam S, Moaven O, Patel P, Malo NS, Ray M, Abtahi SM, Muhammad N, Raychowdhury A, Teshager A, Mohamed MM, Moss AK, Ahmed R, Hakimian S, Narisawa S, Millán JL, Hohmann E, Warren HS, Bhan AK, Malo MS, Hodin RA. Intestinal alkaline phosphatase prevents metabolic syndrome in mice. ProcNatlAcadSci U S A. 2013; 110(17):7003-8. PMID: 23569246

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; 189 (4):2017-22. PMID: 22772444

Angel TE, Jacobs JM, Smith RP, Pasternack MS, Elias S, Gritsenko MA, Shukla A, Gilmore EC, McCarthy C, Camp DG 2nd, Smith RD, Warren HS. Cerebrospinal fluid proteome of patients with acute Lyme disease. J Proteome Res. 2012; 11(10):4814-22. PMID: 22900834

Chan KE, Warren HS, Thadhani RI, Steele DJ, Hymes JL, Maddux FW, Hakim RM. Prevalence and Outcomes of Antimicrobial Treatment for Staphylococcus Aureus Bloodstream Infection in Outpatients with End-Stage Renal Disease. J Am Soc Nephrol. 2012; 23(9):1551-9. PMID: 22904350

Cuschieri J, Johnson JL, Sperry J, West MA, Moore EE, Minei JP, Bankey PE, Nathens AB, Cuenca AG, Efron PA, Hennessy L, Xiao W, Mindrinos MN, McDonald-Smith GP, Mason PH, Billiar TR, Schoenfeld DA, Warren HS, Cobb JP, Moldawer LL, Davis RW, Maier RV, Tompkins RG. Benchmarking Outcomes in the Critically Injured Trauma Patient and the Effect of Implementing Standard Operating Procedures. Ann Surg. 2012; 255(5):993-9. PMID: 22470077

Berra L, Coppadoro A, Yu B, Lei C, Spagnolli E, Steinbicker AU, Bloch KD, Lin T, Sammy FY, Warren HS, Fernandez BO, Feelisch M, Dzik WH, Stowell CP, Zapol WM. Transfusion of stored autologous blood does not alter reactive hyperemia index in healthy volunteers. Anesthesiology. 2012; 117(1):56-63. PMID: 22531338

Xiao W, Mindrinos MN, Seok J, Cuschieri J, Cuenca AG, Gao H, Hayden DL, Hennessy L, Moore EE, Minei JP, Bankey PE, Johnson JL, Sperry J, Nathens AB, Billiar TR, West MA, Brownstein BH, Mason PH, Baker HV, Finnerty CC, Jeschke MG, López MC, Klein MB, Gamelli RL, Gibran NS, Arnoldo B, Xu W, Zhang Y, Calvano SE, McDonald-Smith GP, Schoenfeld DA, Storey JD, Cobb JP, Warren HS, Moldawer LL, Herndon DN, Lowry SF, Maier RV, Davis RW, Tompkins RG; Inflammation and Host Response to Injury Large-Scale Collaborative Research Program. A genomic storm in critically injured humans. J Exp Med. 2011; 208(13):2581-90. PMID: 22110166

Li Y, Si R, Feng Y, Chen HH, Zou L, Wang E, Zhang M, Warren HS, Sosnovik DE, Chao W.Myocardial ischemia activates an injurious innate immune signaling via cardiac heat shock protein 60 and Toll-like receptor 4. J. Biol Chem. 2011; 286(36):31308-19. PMID: 21775438

Ebrahimi F, Malo MS, Alam SN, Moss AK, Yammine H, Ramasamy S, Biswas B, Chen KT, Muhammad N, Mostafa G, Warren HS, Hohmann EL, Hodin RA. Local Peritoneal Irrigation with Intestinal Alkaline Phosphatase Is Protective Against Peritonitis in Mice. J Gastrointest Surg. 2011; 15(5):860-9. PMID: 21360208

Shin H-S , Xu F, Bagchi A, Herrup E, Prakash A, Valentine C, Kulkarni H, Wilhelmsen K, Warren HS, Hellman J. Bacterial lipoprotein Toll-like receptor 2 agonists broadly modulate endothelial function and coagulation pathways in vitro and in vivo. J Immunol. 2011; 186(2):1119-30. PMID: 21169547

Chen KT, Malo MS, Beasley-Topliffe LK, Poelstra K, Millan JL, Mostafa G, Alam SN, Ramasamy S, Warren HS, Hohmann EL, Hodin RA. A Role for Intestinal Alkaline Phosphatase in the Maintenance of Local Gut Immunity. Dig Dis Sci. 2011; 56(4):1020-7. PMID: 20844955

Ramasamy S, Nguyen DD Eston M, Alam SN, Moss AK, Ebrahimi F, Biswas B, Mostafa G, Chen KT, Kaliannan K, Yammine H, Narisawa S, Millán JL, Warren HS, Hohmann EL, Mizoguchi E, Reinecker H, Bhan AK, Snapper SB, Malo MS, Hodin RA. Intestinal Alkaline Phosphatase Has Beneficial Effects in Mouse Models of Chronic Colitis. Inflamm Bowel Dis. 2011; 17(2):532-42. PMID: 20645323

Rajicic N, Cuschieri J, Finkelstein DM, Miller-Graziano CL, Hayden D, Moldawer LL, Moore E, O'Keefe G, Pelik K, Warren HS, Schoenfeld DA, and the Inflammation and the Host Response to Injury Large Scale Collaborative Research Program. Identification and interpretation of longitudinal gene expression changes in trauma. PLoS One. 2010; 5(12):e14380. PMID: 21187951

Kotz KT, Xiao W, Miller-Graziano C, Qian WJ, Russom A, Warner EA, Moldawer LL, De A, Bankey PE, Petritis BO, Camp DG 2nd, Rosenbach AE, Goverman J, Fagan SP, Brownstein BH, Irimia D, Xu W, Wilhelmy J, Mindrinos MN, Smith RD, Davis RW, Tompkins RG, Toner M; the Inflammation and the Host Response to Injury Collaborative Research Program, Baker HV, Balis UG, Billiar TR, Calvano SE, Cobb JP, Cuschieri J, Finnerty CC, Gamelli RL, Gibran NS, Harbrecht BG, Hayden DL, Hennessy L, Herndon DN, Jeschke MG, Johnson JL, Klein MB, Lowry SF, Maier RV, Mason PH, McDonald-Smith GP, Minei JP, Moore EE, Nathens AB, O Keefe GE, Rahme LG, Remick DG, Schoenfeld DA, Shapiro MB, Sperry J, Storey JD, Tibshirani R, Warren HS, West MA, Wispelwey B, Wong WH. Clinical microfluidics for neutrophil genomics and proteomics. Nat Med. 2010; 16(9):1042-7. PMID: 20802500

Zhou B, Xu W, Herndon D, Tompkins R, Davis R, Xiao W, Wong WH; Inflammation and Host Response to Injury Program, Toner M, Warren HS, Schoenfeld DA, Rahme L, McDonald-Smith GP, Hayden D, Mason P, Fagan S, Yu YM, Cobb JP, Remick DG, Mannick JA, Lederer JA, Gamelli RL, Silver GM, West MA, Shapiro MB, Smith R, Camp DG 2nd, Qian W, Storey J, Mindrinos M, Tibshirani R, Lowry S, Calvano S, Chaudry I, West MA, Cohen M, Moore EE, Johnson J, Moldawer LL, Baker HV, Efron PA, Balis UG, Billiar TR, Ochoa JB, Sperry JL, Miller-Graziano CL, De AK, Bankey PE, Finnerty CC, Jeschke MG, Minei JP, Arnoldo BD, Hunt JL, Horton J, Cobb JP, Brownstein B, Freeman B, Maier RV, Nathens AB, Cuschieri J, Gibran N, Klein M, O'Keefe G. Analysis of factorial time-course microarrays with application to a clinical study of burn injury. Proc Natl Acad Sci U S A. 2010; 107(22):9923-8. PMID: 20479259

Malo MS, Alam SN, Mostafa G, Zeller SJ, Johnson PV, Mohammad N, Chen KT, Moss AK, Ramasamy S, Faruqui A, Hodin S, Malo PS, Ebrahimi F, Biswas B, Narisawa S, Millán JL, Warren HS, Kaplan JB, Kitts CL, Hohmann EL, Hodin RA. Intestinal alkaline phosphatase preserves the normal homeostasis of gut microbiota. Gut. 2010; 59(11):1476-84. PMID: 20947883

Chen KT, Malo MS, Moss AK, Zeller S, Johnson P, Ebrahimi F, Mostafa G, Alam S, Ramasamy S, Warren HS, Hohmann E, Hodin RA. Identification of Specific targets for the gut mucosal defense factor intestinal alkaline phosphatase, Am J Physiol Gastrointest Liver Physiol. 2010; 299(2):G467-75. PMID: 20489044

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;202(4):624-32 PMID: 20617898

Warren HS, Fitting C, Hoff E, Beasley-Topliffe L, Tesini B, Liang X, Adib-Conquy M, Valentine C, Hellman J, Hayden D, Cavaillon JM. Resilience to bacterial infection: difference between species could be due to proteins in serum. J Infect Dis. 2010; 201(2):223-32. PMID: 20001600

Cobb JP, Moore EE, Hayden DL, Minei JP, Cuschieri J, Yang J, Li Q, Lin N, Brownstein BH, Hennessy L, Mason PH, Schierding WS, Dixon DJ, Tompkins RG, Warren HS, Schoenfeld DA, Maier RV. Validation of the Riboleukogram to Detect Ventilator-Associated Pneumonia after Severe Injury. Ann Surg. 2009; 250(4):531-9. PMID: 19730236

Warren HS, Elson CM, Hayden DL, Schoenfeld DA, Cobb JP, Maier RV, Moldawer LL, Moore EE, Harbrecht BG, Pelak K, Cuschieri J, Herndon DN, Jeschke MG, Finnerty CC, Brownstein BH, Hennessy L, Mason PH, Tompkins RG. Inflammation and Host Response to Injury Large Scale Collaborative Research Program. Genomic Score Prognostic of Outcome in Trauma Patients. Mol Med. 2009; 15(7-8):220-7. PMID: 19593405

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; 86(2):229-35. PMID: 19395472

Goldberg RF, Austen WG, Zhang X, Munene G, Mostafa G, Biswas S, McCormack, M, Eberlin, K, Nguyen JT, Tatlidede HS, Warren HS, Narisawa S, Malo MS, Millán JL and Hodin RA. Intestinal alkaline phosphatase is a gut mucosal defense factor maintained by enteral nutrition. Proc Natl Acad Sci U S A. 2008; 105(9):3551-6. PMID: 18292227

Bagchi A, Herrup EA, Warren HS, Trigilio J, Shin HS, Valentine C, Hellman J. MyD88 dependent and MyD88 independent pathways in synergy, priming, and tolerance between toll-like receptors agonists. J Immunol. 2007; 178(2):1164-71. PMID: 17202381

Valentine CH, Hellman J, Beasley-Topliffe L, Bagchi A, and Warren HS. Passive immunization to outer membrane proteins MLP and PAL does not protect mice from sepsis. Molecular Medicine. 2006; 12(9-10):252-8. PMID: 17225874

Cobb JP, Mindrinos MN, Miller-Graziano C, Calvano SE, Baker HB, Xiao W, Laudanski K, Brownstein BH, Elson CM, Hayden DL, Herndon DL, Lowry SF, Maier RV, Schoenfeld DA, Moldawer L, Davis RW, Tompkins RG, Inflammation and Host Response to Injury Large-Scale Collaborative Research Program, Baker HB,. Bankey P, Billiar T, Brownstein, BH, Calvano SE Camp D, Chaudry I, Cobb, JP, Davis RW, Elson, CM, Bradley F, Gamelli R, Gibran N, Harbrecht B, Hayden, DL, Haegy W, Deimbach D, Herndon DN, Horton, J, Hunt J, Laudanski K, Lederer J, Lowry SF Maier RV, Mannick J, McKinley B, Miller-Graziano C, Mindrinos MN, Minei J, Moldawer L, Moore E, Moore F, Munford R, Nathens A, O'Keefe K, Purdue, G, Rahme L, Remick D, Sailors M, Schoenfeld D, Shapiro M, Siler G, Smith R, Stephanopoulos G, Stormo G, Tompkins, RG, Toner M, Warren HS, West M, Wolfe S, Xiao W. and Young V. Application of genome-wide expression analysis to human health and disease. Proc Natl Acad Sci U S A. 2005; 102(13):4801-6. PMID: 15781863

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. PMID: 15717270

Copeland S, Warren HS, Lowry SF, Cavlano SE. Remick D and the Inflammation and Host Response to Injury Large Scale Collaborative Research Program. The acute inflammatory response to endotoxin in mice and humans. Clinical and Diagnostic Laboratory Immunology 2005; 12: 60-67. PMID: 15642986

Yang H, Ochani M, Li J, Qiang X, Tanovic M, Harris HE, Susaria SM, Ulloa L, Wang H, DiRaimo R, Czura CJ, Wang H, Roth J, Warren HS, Fink MP, Fenton MJ, Andersson U, Tracey KJ. Reversing established sepsis with antagonists of endogenous HMGB1. Proc Natl Acad Sci U S A. 2004; 101(1): 296-301. PMID: 14695889

Li J, Kokkola R, Tabibzadeh S, Yang R, Ochani M, Qiang X, Harris HE, Czura CJ, Wang H, Ulloa L, Wang H, Warren HS, Moldawer LL, Fink MP, Andersson U, Tracey KJ, Yang H. Structural basis for the proinflammatory cytokine activity of high mobility group box 1. Mol Med. 2003; 9(1-2):37-45. PMID: 12765338

Cross AS, Opal SM, Palardy JE, Drabick JJ, Warren HS, Huber C, Cook P, Bhattaacharajee AK. Phase I study of detoxified Escherichia coli J5 lipopolysaccharide (J5dLPS)/ group B meningococcal outer membrane protein (OMP) complex vaccine in human subjects. Vaccine. 2003; 21(31): 4576-87. PMID: 14575770