Remick, Daniel G. - Boston University

研究领域

The laboratory focuses on investigating the inflammatory response with particular emphasis on cytokines. We are attempting to determine how the inflammatory response results in tissue/organ injury and death. To achieve this goal the laboratory uses a variety of methods ranging from whole animal models to isolated cells with reporter gene constructs. The ultimate focus of the lab is to understand the reaction to inflammation so that it may be modulated to improve health outcomes. It should be specifically noted that the modulation may include either blocking excessive inflammation or augmenting immunosuppression. Common themes: The primary theme which ties together all of the projects is the careful measurement of cytokines. Cytokines are peptide mediators of the inflammatory response which represent critical components. They have been successfully modulated to improve health in patients with severe diseases. There are several discrete projects within the laboratory. Sepsis. Sepsis represents the host response to severe infections and results in substantial morbidity and mortality. The mortality for a septic patient exceeds 30% even in the best care situations. It is also important to note that the mortality for sepsis is calculated on the basis of 28 days survival, rather than the typical five-year survival used for cancer patients. Consequently, the number of years of life lost with sepsis is substantial. Our laboratory attempts to decipher the mechanisms for sepsis induced organ injury and mortality. The studies use a combination of a cell based approaches, whole animal experiments, and exploration of biomarker profiles in patients. Previous work has demonstrated that patients who suffer traumatic injury are at markedly increased risk for the development of sepsis, and its subsequent mortality. We are collecting plasma from patients who suffered a severe traumatic injury in a longitudinal fashion in order to determine if there is a biomarker profile which predicts both the development of sepsis, and that the outcome once a patient becomes a septic. Asthma. Asthma represents another significant inflammatory condition with tremendous annual health-care costs. Our laboratory has developed a novel model of asthma like a pulmonary inflammation. Among children in inner cities, the major allergen which induces asthma comes from cockroaches rather than dog or cat allergens, or pollen. We collected dust from the homes were children had asthma and used this to induce inflammation in a mouse. the model was remarkably robust and produced several of the features observed in patients with asthma including the pulmonary recruitment of eosinophils, neutrophils, as well as mucous hyperplasia, and airways hyperreactivity. We have begun to use this model to explore novel treatments for asthma. Tumor necrosis factor (TNF) is a poorly named inflammatory mediator which actually has little to do with the necrosis of tumors. However, it is an important regulator of many aspects of chronic inflammation. Inhibitors of TNF have been used for years in the treatment of chronic inflammatory conditions such as rheumatoid arthritis. We were one of the first labs to demonstrate that blocking the biological activity of TNF could improve asthma. Panel A in the figure shows a lung from an animal which has been treated with an antibody directed against TNF. This is essentially normal histology with very little inflammation. In contrast, panel B shows an animal which received a control antibody. There are several dark purple dots surrounding the blood vessels and airways. These purple areas represent the nuclei of the inflammatory cells which have been elicited as part of the asthmatic response.

近期论文

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Rosenzweig M, Seldin DC, Remick DG, Skinner M, Quillen K, Oran B, Finn KT, Sanchorawala V: Febrile reactions occurring with second cycle of high-dose melphalan and SCT in patients with AL amyloidosis: a ‘melphalan recall’ reaction, Bone Marrow Transplant 2010, 45:21-24, PMID: 19421171 Horton DL, Remick DG: Delayed addition of glucocorticoids selectively suppresses cytokine production in stimulated human whole blood, Clin Vaccine Immunol 2010, 17:979-985 PMID: 20445007 Draganov D, Teiber J, Watson C, Bisgaier C, Nemzek J, Remick D, Standiford T, La Du B: PON1 and Oxidative Stress in Human Sepsis and an Animal Model of Sepsis, Adv Exp Med Biol 2010, 660:89-97, PMID: 20221873 Zhou B, Xu W, Herndon D, Tompkins R, Davis R, Xiao W, Wong WH, 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, 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, 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, 107:9923-9928, PMID: 20479259 Cuschieri J, Bulger E, Schaeffer V, Sakr S, Nathens AB, Hennessy L, Minei J, Moore EE, O’Keefe G, Sperry J, Remick D, Tompkins R, Maier RV: Early Elevation in Random Plasma Il-6 after Severe Injury Is Associated with Development of Organ Failure, Shock 2010, 34:346-351, PMID: 20844410 Natarajan S, Kim J, Remick DG: Chronic pulmonary LPS tolerance induces selective immunosuppression while maintaining the neutrophilic response, Shock 2010, 33:162-169, PMID: 19487981 Osuchowski MF, Craciun FL, Schuller E, Sima C, Gyurko R, Remick DG: Untreated type 1 diabetes increases sepsis-induced mortality without inducing a prelethal cytokine response, Shock 2010, 34:369-376, PMID: 20610941 Uddin J, Gonzalez AE, Gilman RH, Thomas LH, Rodriguez S, Evans CA, Remick DG, Garcia HH, Friedland JS: Mechanisms regulating monocyte CXCL8 secretion in neurocysticercosis and the effect of antiparasitic therapy, J Immunol 2010, 185:4478-4484, PMID: 20826750 Vaickus LJ, Bouchard J, Kim J, Natarajan S, Remick DG: Assessing pulmonary pathology by detailed examination of respiratory function, Am J Pathol 2010, 177:1861-1869, PMID: 20724595 Vaickus LJ, Bouchard J, Kim J, Natarajan S, Remick DG: Oral Tolerance Inhibits Pulmonary Eosinophilia in a Cockroach Allergen Induced Model of Asthma: A Randomized Laboratory Study, Respir Res 2010, 11:160, PMID: 21092270 Craciun FL, Schuller ER, Remick DG: Early enhanced local neutrophil recruitment in peritonitis-induced sepsis improves bacterial clearance and survival, J Immunol 2010, 185:6930-6938, PMID: 21041722 Vaickus LJ, Bouchard J, Kim J, Natarajan S, Remick DG: Inbred and outbred mice have equivalent variability in a cockroach allergen-induced model of asthma, Comp Med 2010, 60:420-426, PMID: 21262127 Stearns-Kurosawa DJ, Osuchowski MF, Valentine C, Kurosawa S, Remick DG: The Pathogenesis of Sepsis, Annu Rev Pathol 2011, 6:19-48, PMID: 20887193 Natarajan S, Kim J, Bouchard J, Cruikshank W, Remick DG: Reducing LPS content in cockroach allergens increases pulmonary cytokine production without increasing inflammation: A randomized laboratory study, BMC Pulm Med 2011, 11:12, PMID: 21345191 Belikoff BG, Hatfield S, Georgiev P, Ohta A, Lukashev D, Buras JA, Remick DG, Sitkovsky M: A2B adenosine receptor blockade enhances macrophage-mediated bacterial phagocytosis and improves polymicrobial sepsis survival in mice, J Immunol 2011, 186:2444-2453, PMID: 21242513 Belikoff B, Hatfield S, Sitkovsky M, Remick DG: Adenosine Negative Feedback on A2A Adenosine Receptors Mediates Hyporesponsiveness in Chronically Septic Mice, Shock 2011, 35:382-387, PMID: 21192284 Kim J, Natarajan S, Bae H, Jung SK, Cruikshank W, Remick DG: Herbal medicine treatment reduces inflammation in a murine model of cockroach allergen-induced asthma, Ann Allergy Asthma Immunol 2011, 107:154-162, PMID: 21802024 Kong X, Thimmulappa R, Craciun F, Harvey C, Singh A, Kombairaju P, Reddy SP, Remick D, Biswal S: Enhancing Nrf2 Pathway by Disruption of Keap1 in Myeloid Leukocytes Protects Against Sepsis, Am J Respir Crit Care Med 2011, PMID: 21799073 Asimaki A, Tandri H, Duffy ER, Winterfield JR, Mackey-Bojack S, Picken MM, Cooper LT, Wilber DJ, Marcus FI, Basso C, Thiene G, Tsatsopoulou A, Protonotarios N, Stevenson WG, McKenna WJ, Gautam S, Remick DG, Calkins H, Saffitz JE: Altered desmosomal proteins in granulomatous myocarditis and potential pathogenic links to arrhythmogenic right ventricular cardiomyopathy, Circ Arrhythm Electrophysiol 2011, 4:743-752, PMID: 21859801 Kim J, Natarajan S, Vaickus LJ, Bouchard JC, Beal D, Cruikshank WW, Remick DG: Diesel exhaust particulates exacerbate asthma-like inflammation by increasing CXC chemokines, Am J Pathol 2011, 179:2730-2739, PMID: 21967814 Chiswick EL, Duffy E, Japp B, Remick D: Detection and quantification of cytokines and other biomarkers, Methods Mol Biol 2012, 844:15-30, PMID: 22262432 Moitra R, Beal DR, Belikoff BG, Remick DG: Presence of preexisting antibodies mediates survival in sepsis, Shock 2012, 37:56-62, PMID: 21921828 Natarajan S, Kim J, Bouchard J, Cruikshank W, Remick DG: Pulmonary Endotoxin Tolerance Protects against Cockroach Allergen-Induced Asthma-Like Inflammation in a Mouse Model, Int Arch Allergy Immunol 2012, 158:120-130, PMID: 22269653 Winfield RD, Delano MJ, Cuenca AG, Cendan JC, Lottenberg L, Efron PA, Maier RV, Remick DG, Moldawer LL, Cuschieri J: Obese Patients Show a Depressed Cytokine Profile Following Severe Blunt Injury, Shock 2012, PMID: 22266966