Department of Pathology, Microbiology, and Immunology


   Edward R. Sherwood, M.D., Ph.D. s

Vice Chair for Research, Dept. of Anesthesiology
Dept. of Pathology, Microbiology and Immunology

Contact Information

Office Location
B4220 MCN

Phone:  615-322-2564
E-mail: edward.r.sherwood@vanderbilt.edu

Campus Mail address:
T-4202 MCN (2520)

US Mailing address:
Vanderbilt University School of Medicine
Anesthesiology Research Division
T-4202 MCN
1161 21st Ave South

Nashville, TN 37232-2520






MD, University of Chicago
PhD, Tulane University
BS, Southwestern University



Research Keywords



sepsis, inflammation, immunomodulation, chemokines, natural killer cells, TLR agonists



Research Description



The Sherwood research group is studying several aspects of sepsis and the systemic inflammatory response syndrome. A major interest is to define mechanisms of sepsis-induced systemic inflammation and organ injury with emphasis on the roles of natural killer (NK) and T lymphocytes. Current studies are being performed to evaluate the mechanisms of NK and T cell activation and chemotaxis during sepsis with emphasis on the chemokine receptor CXCR3 and its ligands, CXCL9 and CXCL10. The Sherwood group showed that CXCR3 activation is crucial for NK cell trafficking during sepsis and that CXCR3 blockade will decrease inflammation and organ injury in experimental models of sepsis. The underlying goal is to further understand the contribution of CXCR3 activation in the pathogenesis of sepsis and develop clinically relevant interventions to block CXCR3 and improve outcome.
In further studies, the Sherwood group is evaluating the immunomodulatory properties of TLR4 agonists and their ability to modify the host response to systemic infection. The group showed that the TLR4 agonists lipopolysaccharide and monophosphoryl lipid A are potent immunomodulators that alter systemic cytokine production and enhance innate resistance to bacterial infections. The improved resistance to infection is caused by neutrophil expansion and enhanced neutrophil functions. The group is working to define the mechanisms by which TLR4 agonists promote the antimicrobial functions of neutrophils and develop TLR4 agonists as agents that can be used clinically to improve the resistance of critically ill patients to infection.



Clinical Research Description



The clinical research interests of the Sherwood group are focused on evaluation adn treatment of sepsis-associated immunosuppression with emphasis on lymphocyte dysfunction and exhaustion. Current projects are assessing the correlation of lymphocyte dysfunction with outcome in patients wit hmajor trauma and burns. Studies are being conducted to assess lymphocyte function (apoptosis, proliferation, secretory activity)and biomarkers (PD-1, CTLA-4, BTLA) and their correlation with clinical outcomes (nosocomial infection, ventilator days, complication rate). Future interests are in developing agents to improve immune function in critically ill patients.






Herzig, DS, Guo, Y, Fang, G, Toliver-Kinsky, TE, Sherwood, ER. Therapeutic Efficacy of CXCR3 Blockade in an Experimental Model of Severe Sepsis. Crit Care, 16(5), R168, 2012

Herzig, DS, Driver, BR, Fang, G, Toliver-Kinsky, TE, Shute, EN, Sherwood, ER. Regulation of lymphocyte trafficking by CXC chemokine receptor 3 during septic shock. Am J Respir Crit Care Med, 185(3), 291-300, 2012

Herzig, D, Fang, G, Toliver-Kinsky, TE, Guo, Y, Bohannon, J, Sherwood, ER. Stat1-deficient mice are resistant to cecal ligation and puncture-induced septic shock. Shock, 38(4), 395-402, 2012

Watts, BA, George, T, Sherwood, ER, Good, DW. Basolateral LPS inhibits NHE3 and HCOFormula absorption through TLR4/MyD88-dependent ERK activation in medullary thick ascending limb. Am J Physiol Cell Physiol, 301(6), C1296-306, 2011

Romero, CD, Varma, TK, Hobbs, JB, Reyes, A, Driver, B, Sherwood, ER. The Toll-like receptor 4 agonist monophosphoryl lipid a augments innate host resistance to systemic bacterial infection. Infect Immun, 79(9), 3576-87, 2011

Romero, CR, Herzig, DS, Etogo, A, Nunez, J, Mahmoudizad, R, Fang, G, Murphey, ED, Toliver-Kinsky, T, Sherwood, ER. The role of interferon-I? in the pathogenesis of acute intra-abdominal sepsis. J Leukoc Biol, 88(4), 725-35, 2010

Talon, MD, Woodson, LC, Sherwood, ER, Aarsland, A, McRae, L, Benham, T. Intranasal dexmedetomidine premedication is comparable with midazolam in burn children undergoing reconstructive surgery. J Burn Care Res, 30(4), 599-605, 2009

Enoh, VT, Lin, SH, Etogo, A, Lin, CY, Sherwood, ER. CD4+ T-cell depletion is not associated with alterations in survival, bacterial clearance, and inflammation after cecal ligation and puncture. Shock, 29(1), 56-64, 2008

Murphey, ED, Fang, G, Sherwood, ER. Endotoxin pretreatment improves bacterial clearance and decreases mortality in mice challenged with Staphylococcus aureus. Shock, 29(4), 512-8, 2008

Etogo, AO, Nunez, J, Lin, CY, Toliver-Kinsky, TE, Sherwood, ER. NK but not CD1-restricted NKT cells facilitate systemic inflammation during polymicrobial intra-abdominal sepsis. J Immunol, 180(9), 6334-45, 2008

Murphey, ED, Fang, G, Sherwood, ER. Pretreatment with the Gram-positive bacterial cell wall molecule peptidoglycan improves bacterial clearance and decreases inflammation and mortality in mice challenged with Staphylococcus aureus. Crit Care Med, 36(11), 3067-73, 2008

Murphey, ED, Sherwood, ER. Pretreatment with the Gram-positive bacterial cell wall molecule peptidoglycan improves bacterial clearance and decreases inflammation and mortality in mice challenged with Pseudomonas aeruginosa. Microbes Infect, 10(12-13), 1244-50, 2008

Murphey, ED, Fang, G, Varma, TK, Sherwood, ER. Improved bacterial clearance and decreased mortality can be induced by LPS tolerance and is not dependent upon IFN-gamma. Shock, 27(3), 289-95, 2007

Enoh, VT, Lin, SH, Lin, CY, Toliver-Kinsky, T, Murphey, ED, Varma, TK, Sherwood, ER. Mice depleted of alphabeta but not gammadelta T cells are resistant to mortality caused by cecal ligation and puncture. Shock, 27(5), 507-19, 2007

Murphey, ED, Sherwood, ER. Bacterial clearance and mortality are not improved by a combination of IL-10 neutralization and IFN-gamma administration in a murine model of post-CLP immunosuppression. Shock, 26(4), 417-24, 2006

Enoh, VT, Fairchild, CD, Lin, CY, Varma, TK, Sherwood, ER. Differential effect of imipenem treatment on wild-type and NK cell-deficient CD8 knockout mice during acute intra-abdominal injury. Am J Physiol Regul Integr Comp Physiol, 290(3), R685-93, 2006

Enoh, VT, Lin, CY, Varma, TK, Sherwood, ER. Differential effect of imipenem treatment on injury caused by cecal ligation and puncture in wild-type and NK cell-deficient beta(2)-microgloblin knockout mice. Am J Physiol Gastrointest Liver Physiol, 290(2), G277-84, 2006

Huang, Z, Pereira, C, Toliver-Kinsky, T, Murphey, ED, Varma, TK, Lin, CY, Herndon, DN, Sherwood, ER. Effect of transforming growth factor-beta neutralization on survival and bacterial clearance in a murine model of Pseudomonas aeruginosa burn wound infection. J Burn Care Res, 27(5), 682-7, 2006

Tao, W, Enoh, VT, Lin, CY, Johnston, WE, Li, P, Sherwood, ER. Cardiovascular dysfunction caused by cecal ligation and puncture is attenuated in CD8 knockout mice treated with anti-asialoGM1. Am J Physiol Regul Integr Comp Physiol, 289(2), R478-R485, 2005

Varma, TK, Durham, M, Murphey, ED, Cui, W, Huang, Z, Lin, CY, Toliver-Kinsky, T, Sherwood, ER. Endotoxin priming improves clearance of Pseudomonas aeruginosa in wild-type and interleukin-10 knockout mice. Infect Immun, 73(11), 7340-7, 2005