Trauma and Inflammation
Research Training Fellowship
Division of Surgical Research, Department of SurgeryRhode Island Hospital, Lifespan
Brown Medical School
Faculty Research Program
Dr. Albina is Professor of Surgery, Brown Medical School and the Director of Surgical Research in the Department of Surgery at Rhode Island Hospital. Dr. Albina's research interests continue to be the functional characterization of inflammatory cells during wound healing and repair.Selected Publications:
Meszaros, A.J., Reichner, J.S., and Albina, J.E. Macrophage phagocytosis of wound neutrophils. Journal of Leukocyte Biology 65:35-42, 1999.
Meszaros, A.J., Reichner, J.S., and Albina, J.E. Macrophage-induced neutrophil apoptosis. Journal of Immunology 165:435-441, 2000
Nessel, C.C., Henry, W.L., Jr., Mastrofrancesco, B., Reichner, J.S., and Albina, J.E. Vestigial respiratory burst activity in wound macrophages. American Journal of Physiology 276: R1587-R1594, 1999.
Albina, J.E., Mastrofrancesco, B., Vessella, J.A., Louis, C.A., Henry, W.L., Jr., and Reichner, J.S. HIF-1 expression in healing wounds: HIF-1alpha induction in primary inflammatory cells by TNF-alpha. American Journal of Physiology 281: C1971-C1977, 2001.
Mahoney, E., Reichner, J., Robinson Bostom, L., Mastrofrancesco, B., Henry, W., and Albina, J. Bacterial colonization and the expression of inducible nitric oxide synthase (iNOS) in murine wounds. American Journal of Pathology 161:2143-2152, 2002.
Dr. Ayala is Professor of Surgery, Brown University.Dr. Ayala's research interests include differential effects of sepsis on immune cell function. The role of programmed cell death in immune dysfunction observed following hemorrhage and/or sepsis. Apoptotic processes in priming for acute lung injury resultant from shock.
Selected Publications:
Song, G.Y., Chung, C.S., Chaudry, I.H., Ayala, A. 2001. MAPK p38 antagonism as a novel method of inhibiting lymphoid immune suppression in polymicrobial sepsis. Amer. J. Physiol. 281:C662-C669
Ayala, A., Chung, C.S., Lomas, J.L., Song, G.Y., Doughty, L.A., Gregory, S.H., Cioffi,W.G., LeBlanc, B.W., Reichner, J., Simms, H.H., Grutkoski, P.S. 2002. Shock induced neutrophil mediated priming for acute lung injury in mice: divergent effects of TLR-4 and TLR-4/FasL deficiency. Amer. J. Pathology 161:2283-2294
Lomas, J.L., Chung, C.S., Grutkoski, P.S., LeBlanc, B.W., Lavigne, L., Reichner, J., Gregory, S.H., Doughty, L.A., Cioffi, W.G., Ayala, A. 2003. Differential effects of MIP-2 and KC on hemorrhage induced neutrophil priming for lung inflammation: assessment by adoptive cell transfer in mice. Shock 19:358-365.
Chung, C.S., Song, G.Y., Lomas, J.L., Simms, H.H., Chaudry, I.H., Ayala, A. 2003. Inhibition of Fas/Fas ligand (FasL) signaling during sepsis has tissue specific effects on macrophage apoptotic and functional capacity. J. Leukocyte Biol. 74:344-351
Grutkoski, P.S., Chen, Y., Chung, C.S., Ayala, A. 2003. Sepsis-induced SOCS-3 expression is immunologically restricted to phagocytes. J. Leukocyte Biol. 74:916-922
Dr. Bereiter received his Ph.D. from the University of Illinois (Physiology) in 1976, spent four years as a postdoctoral fellow in Geneva, Switzerland (neuroendocrinology) under the mentorship of Dr. Bernard Jeanrenaud, and joined Brown University in 1980. He was appointed Professor in 1995. Dr. Bereiter's research interests include central neural mechanisms in orofacial pain as well as the basis for sex differences and hormonal influences on pain sensation.Selected Publications:
Meng I.D., Hu J.W., Bereiter D.A. Differential effects of morphine on corneal-responsive neurons in rostral versus caudal regions of spinal trigeminal nucleus in the rat. J Neurophysiol 79:2593-2602, 1998.
Hirata, H., Takeshita, S., Hu, J.W. and Bereiter, D.A. Cornea–responsive medullary dorsal horn neurons: modulation by local opioid agonists and projections to thalamus and brainstem in the rat. J. Neurophysiol. 84:1050-1061, 2000.
Okamoto, K., Hirata, H., Takeshita, S., and Bereiter, D. A. Response properties of TMJ neurons in superficial laminae at the spinomedullary junction of female rats vary over the estrous cycle. J. Neurophysiol. (in press), 2002
Walter L. Biffl, M.D. (Associate Faculty)
Dr. Biffl is currently Chief of the Division of Trauma/Surgical Critical Care at Rhode Island Hospital and Associate Professor of Surgery at Brown Medical School. Dr. Biffl's research interests are to determine how blood transfusion affects neutrophil functional lifespan independent of tissue injury. The long-term goal of this work is to identify clinically-accessible means of attenuating the adverse immunomodulatory effects of blood transfusion, which may be attributable to neutrophil priming.Selected Publications:
Biffl W.L., Moore E.E., Zallen G., Johnson J.L., Gabriel J., Offner P.J., Silliman C.C. Neutrophils are primed for cytotoxicity and resist apoptosis in injured patients at risk for multiple organ failure. Surgery, 126:198-202, 1999
Gonzalez R.J., Moore E.E., Biffl W.L., Ciesla D.J., Silliman C.C. The lipid fraction of post-hemorrhagic shock mesenteric lymph inhibits neutrophil apoptosis and enhances cytotoxic potential. Shock 14:404-408, 2000.
Biffl W.L., Moore E.E., Offner P.J., Ciesla D.J., Gonzalez R.J., Silliman C.C. Aged stored packed red blood cells delay neutrophil apoptosis and prime neutrophils for cytotoxicity: Abrogation by packed red blood cell washing but not prestorage leukodepletion. Journal of Trauma, 50:426-432, 2001.
Biffl W.L., West K.E., Moore E.E., Gonzalez R.J., Offner P.J., Silliman C.C. Neutrophil apoptosis is delayed by trauma patients’ plasma via a mechanism involving proinflammatory phospholipids and protein kinase C. Surgical Infections 2:289-295, 2001.
Dr. Biron is the Esther Elizabeth Brintzenhoff Professor of Medical Sciences and the Chair of the Department of Molecular Microbiology and Immunology. Dr. Biron's research interests include the regulation of innate and acquired immune responsesSelected Publications:
Salazar-Mather, T.P., T.A. Hamilton, and C.A. Biron. A chemokine to cytokine to chemokine cascade critical in antiviral defense. J. Clin. Invest. 105:985-93, 2000.
Nguyen L.B., Cousens L.P., Doughty L.A., Pien G.C., Durbin J.E., Biron C.A. IFN-?/?-Mediated Inhibition and Promotion of IFN-?: STAT1 Resolves a Paradox. Nature Immunology. 1(1): 70-76, 2000.
Doughty L.A., Nguyen K.B., Durbin J.E., and Biron C.A. A Role for IFN-?? in Virus Infection-Induced Sensitization to Endotoxin. J Immunol. 166:2658-2664, 2001.
Nguyen K.B., Watford W.T., Salomon R., Hofmann SR, Pien G.C., Morinobu A., Gadina M., O'Shea J.J., Biron C.A. Critical role for STAT4 activation by type 1 interferons in the interferon-gamma response to viral infection. Science 297:2063-6, 2002.
Eugene Chin, M.D., Ph.D. (Associate Faculty)
Dr. Chin is an Associate Professor in the Division of Surgical Research. Dr. Chin's laboratory uses a combination of molecular, biochemical, and cell biological approaches to study mechanisms by which the Jak-STAT signal transduction pathway controls cell growth or death.Selected Publications:
Welte, T., et al. STAT5 interaction with the T cell receptor complex and stimulation of T Cell proliferation. Science. 283:222-225, 1999.
Wang, Y., Wu TR, Cai S, Welte T, Chin YE. Stat1 as a component of tumor necrosis factor alpha receptor 1-TRADD signaling complex to inhibit NF-kappaB activation. Mol. Cell Biol. 20:4505-4512, 2000.
Xia L, Wang L, Chung AS, Ivanov SS, Ling MY, Dragoi AM, Platt A, Gilmer TM, Fu XY, Chin YE. Identification of both the positive and negative motifs for STAT activation within EGFR cytoplasmic domain. J. Biol. Chem. 277:30716-30723, 2002.
Leslie Doughty, M.D. (Associate Faculty)
Dr. Doughty is presently a pediatric intensivist in the Division of Pediatric Critical Care, Rhode Island Hospital and Assistant Professor of Pediatrics in the Brown Medical School. Dr. Doughty's research interests are to assess priming of the innate immune response using models of polymicrobial sepsis and hemorrhagic shock. The long term translational application of this work is to identify novel therapeutic approaches to problems in pediatric sepsis and injurySelected Publications:
Doughty L.A., Nguyen K.B., Durbin J.E., and Biron C.A. A Role for IFN-?? in Virus Infection-Induced Sensitization to Endotoxin. J Immunol. 166:2658-2664, 2001.
Doughty L.A., Clark R., Kaplan S., Dickman P., Sasser H., Wisniewski S., and Carcillo J. sFas and sFas Ligand in Pediatric Sepsis-Induced Multiple Organ Failure Syndrome. Peds Res. (in press), 2002.
Nguyen L.B., Cousens L.P., Doughty L.A., Pien G.C., Durbin J.E., Biron C.A. IFN-?/?-Mediated Inhibition and Promotion of IFN-?: STAT1 Resolves a Paradox. Nature Immunology. 1(1): 70-76, 2000.
Doughty L.A. Modulation of the immune response in critical illness/injury. For Molecular Mechanisms of Critical Illness. Eds. Doughty L. and Linden P. Kluwer Academic Publishers, Norwell, MA, (in press), 2002.
Dr. Johanson is Professor in the Departments of Clinical Neurosciences and Physiology at Brown University and Director of Cerebrospinal Fluid Laboratory at Rhode Island Hospital. Dr. Johanson's research interests include transient full-brain ischemia and growth factors, growth factors and neuropeptides, and neurohormonal regulation of choroid plexus-CSF system.Selected Publications:
Chodobski, A., Szmydynger-Chodobska, J. and C.E. Johanson. Angiotensin II regulates blood flow to choroid plexuses by interacting with the sympathetic nervous system and nitric oxide synthesis. Brain Res. 816: 518-526, 1999.
Johanson, C.E., Szmydynger-Chodobska, J., Chodobski, A., Baird, A., McMillan, P. and E.G. Stopa. Altered formation and bulk absorption of cerebrospinal fluid in FGF-2- induced hydrocephalus. Am. J. Physiol. (Reg. Integ. Comp.) 277: R263-R271, 1999.
Johanson, C.E., Palm, D.E., Primiano, M.J., McMillan, P.N., Chan, P., Knuckey, N.W. and E.G. Stopa. Choroid plexus recovery after transient forebrain ischemia: Role of growth factors and other repair mechanisms. Cellular and Molec. Neurobiol., 20 (2): 197-216, 2000.
Dr. Kane is Professor of Pathology and Chair of the Department of Pathology and Laboratory Medicine at Brown Medical School. Dr. Kane’s research interests include mechanisms of mesothelial cell injury and neoplasia induced by asbestos, animal models of malignant mesothelioma and pathogenesis of mesenchymal tumors induced by asbestos.Selected Publications:
Goodglick L.A., Vaslet C.A., Messier N.J., Kane A.B. Growth factor responses and protooncogene expression of murine mesothelial cell lines derived from asbestos-induced mesotheliomas. Toxicol Pathol. 25:565-73, 1997.
Goodglick L.A., Kane A.B. The role of reactive oxygen metabolites in crocidolite asbestos toxicity to macrophages. Cancer Res 46:5558-5566, 1986.
Cora E.M., Kane A.B. Alterations in a tumor suppressor gene, p53, in mouse mesotheliomas induced by crocidolite asbestos. Eur Resp Rev 3:148-150, 1993.
Goodglick L.A., Kane A.B. Cytotoxicity of long and short crocidolite asbestos fibers in vivo and in vitro. Cancer Res 50:5153-5163, 1990.
James R. Klinger, M.D.(Associate Faculty)
Dr. Klinger is a graduate of the Medical College of Wisconsin. He joined the Brown faculty as Assistant Professor of Medicine in 1996. Dr. Klinger’s research interests include the role of NO in the management of ARDS, the mechanisms of pulmonary response to hypoxia.Selected Publications:
Preston I.R., Klinger J.R., Mehta S., and Hill N.S. Pulmonary edema in scleroderma patients given inhaled nitric oxide. Chest 121:656, 2002.
Preston, I.R., Klinger J.R., Landzberg M.J., Houtchens J., Neslon D., and Hill N.S. Vasoresponsiveness of pulmonary hypertension associated with sarcoidosis. Chest 120:866-872, 2001.
Mehta S., Short K., Schwartz, W., Nelson D., Levy M., Hill N.S., Simms H.H., Klinger J.R. A controlled trial of inhaled nitric oxide in patients with the acute respiratory distress syndrome J Appl Research 1:73-84, 2001.
Mehta, S., Nelson D.L., Klinger J.R., Buczko G.B., Levy M. Prediction of post-extubation work of breathing. Crit Care Med. 28:1341-1346, 2000.
Dr. Reichner is an Associate Professor in the Department of Surgery at Brown Medical School and Deputy Program Director of the Graduate Program in Pathobiology. Dr. Reichner's research interests include macrophage biology and the characterization of the ß-glucan receptor during normal and septic conditions.Selected Publications:
Hofer, S.O.P., Molema, G., Hermens, R.A., Wanebo, H.J., and Reichner, J.S. The effect of surgical wounding on tumor development. Eur. J. Surg. Oncol. 25:231-243, 1999
Harler, M.B., Wakshull, E., Filardo, E.J., Albina, J.E. and Reichner, J.S. Promotion of neutrophil chemotaxis by ß-glucan through differential regulation of ß1 and ß2 integrins. Journal of Immunology 162:6792-6799, 1999.
Harler, M.B. and Reichner, J.S. Increased neutrophil motility by ß-glucan in the absence of chemoattractant. SHOCK 16:419-424, 2001.
Mahoney, E., Reichner, J., Robinson Bostom, L., Mastrofrancesco, B., Henry, W., and Albina, J. Bacterial colonization and the expression of inducible nitric oxide synthase (iNOS) in murine wounds. American Journal of Pathology 161:2143-2152, 2002.
Dr. Rounds is a Professor of Medicine and of Pathology and Laboratory Medicine at Brown Medical School. Dr. Rounds’ research interests include mechanisms of acute endothelial cell injury and pulmonary hypertension.Selected Publications:
Harrington, E.O., Smeglin, A., Newton, J., Ballard, G., and S. Rounds. Adenosine/homocysteine-induced disruption of endothelial cell focal adhesion contacts requires protein tyrosine phosphatase and caspase activity. Am J Physiol. Lung Cell and Molec Physiol. 280:L342-L353, 2001.
Bellas, R., Harrington, E.O., Sheahan, K.L., Newton, J., and S. Rounds. Over-Expression of focal adhesion kinase protects against adenosine/homocysteine-induced apoptosis. Am J Physiol. Lung Cell Molec Physiol. 282:L1135-L1142, 2002.
Kramer K., Harrington E.O., Bellas R., Newton J., Sheahan K.L., and S. Rounds. Isoprenylcysteine carboxyl methyltransferase activity modulates endothelial cell apoptosis. Molecular Biology of the Cell, (in press), 2003.
Professor of Molecular Biology, Cell Biology and Biochemistry at Brown University and director for the Center of Biomedical Research Excellence (COBRE) grant that supports the Center for Genetics and Genomics at Brown. Dr. Sedivy's laboratory investigates the role and regulation of c-Myc, the modulation of replicative cellular senescence of human cells, and the cellular and molecular biology of Raf Kinase Inhibitor Protein (RKIP), a novel inhibitor of MAP kinase and NF-KB. His laboratory is particularly interested in determining the role of RKIP in the modulation of apoptosis and inflammation.Selected Publications:
Hermeking, H., Rago, C., Schuhmacher, M., Li, Q., Barrett, J.F., Obaya, A.J., O'Connell, B.C., Mateyak, M.K., Tam, W., Kohlhuber, F., Dang, C.V., Sedivy, J.M., Eick, D., Vogelstein, B. and Kinzler, K.W. Identification of CDK4 as a target of c-MYC. Proc. Natl. Acad. Sci. U. S. A. 97: 2229-2234, 2000.
Bazarov, A.V., Adachi, S., Li, S., Mateyak, M.K., Wei, S. and Sedivy, J.M. A modest reduction in c-Myc expression has minimal effects on cell growth and apoptosis but dramatically reduces susceptibility to Ras and Raf transformation. Cancer Res. 61: 1178-1186, 2001.
Adachi, S., Obaya, A.J., Han, Z., Ramos-Desimone, N., Wyche, J.H. and Sedivy, J.M. c-Myc is necessary for DNA damage-induced apoptosis in the G2 phase of the cell cycle. Mol. Cell. Biol., 15:4929-4937, 2001.
Dr. Smith is Professor of Medicine and Director of the Hallet Diabetes Center at Brown Medical School and Director of the Division of Endocrinology.Dr. Smith research interests include metabolic problems that accompany trauma including resistance to anabolic hormones.
Selected Publications:
Mao Y., Ling P.R., Fitzgibbons T.P., McCowen K.C., Frick G.P., Bistrian B.R., Smith R.J. Endotoxin-induced inhibition of growth hormone receptor signaling in rat liver in vivo. Endocrinology 140:5505-5515, 1999.
Giorgino F., de Robertis O., Laviola L., Montrone C., Perrini S., McCowen K.C., Smith R.J. The sentrin-conjugating enzyme mUbc9 interacts with GLUT4 and GLUT1 glucose transporters and regulates transporter levels in skeletal muscle cells. Proc Natl Acad Sci 97:1125-1130, 2000.
Ling P.R., Smith R.J., Mueller C., Mao Y., Bistrian B.R. Inhibition of IL-6-activated JAK/STAT but not MAP kinase signaling in liver of endotoxin-treated rats. Crit Care Med 30:202-211, 2002.
Dr. Tracy is currently Professor of Surgery and Pediatrics at Brown Medical School and Pediatric Surgeon in Chief of the Hasbro Children’s Hospital. Dr. Tracy's research interests include cellular and molecular mechanisms of repair following liver injury.Selected Publications:
Ramm G.A., Carr S.C., Bridle K.R., Li L., Britton R.S., Crawford D.H., Vogler C.A., Bacon B.R., Tracy T.F., Jr. Morphology of liver repair following cholestatic liver injury: resolution of ductal hyperplasia, matrix deposition and regression of myofibroblasts. Liver 20:387-96, 2000.
Roggin K.K., Papa E.F., Kurkchubasche A.G, Tracy T.F., Jr. Kupffer cell inactivation delays repair in a rat model of reversible biliary obstruction. J Surg Res.90(2):166-73, 2001.
Roggin K.K., Kim J.C., Kurkchubasche A.G., Papa E.F., Vezeridis A.M., Tracy T.F., Jr. Macrophage phenotype during cholestatic injury and repair: the persistent inflammatory response. J Pediatr Surg 36:220-228, 2001.
Dr. Wands is the Jeffery and Kimberly Greenberg-Artemis and Martha Joukowsky Professor in Gastroenterology and Professor of Medical Science. He is also the Chief of the Division of Gastroenterology, Lifespan-Rhode Island Academic Medical Center, and Director of the Liver Research Center. Dr. Wand's research interests include cloning and increased expression of an insulin receptor substrate -1 like gene and human hepatocellular carcinoma; hepatitis B and C infection in alcohol-induced liver disease; expression and phosphorylation of insulin receptor substrate-1 during liver regeneration; TGF beta-I-induced apoptosis, cellular and humoral immune responses to hepatitis C virus, and carboxypeptidase-d as a hepatitis B virus receptor.Selected Publications:
Tong, S., Li, J., Wands J.R. Carboxypeptidase D is an avian hepatitis B virus receptor. J Virol 73:8696-8702, 1999.
Li, J., Tong. S., Wands J.R. Identification and expression of glycine decarboxylase (p120) as a duck hepatitis B virus pre-S envelope-binding protein. J Biol Chem 274:27658-27665, 1999.
Ince, N., de la Monte S.M., Wands J.R. Overexpression of human aspartyl (asparaginyl) ?-hydroxylase is associated with malignant transformation. Cancer Res 60:1261-1266, 2000.
