Former Training Grant Residents
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PGY 2 Resident Department of Surgery Rhode Island Hospital Term: 7/2004 - 6/2006 |
Education:
2006 - Present; Surgical Residency
2001 - M.D., Drexel University College of Medicine, Philadelphia, PA
1994 - B.A., Biology, Harvard University, Cambridge, MA
Lab Research:
Dr. Connolly's work concentrated primarily in developing techniques for laser capture microdissection/RNA extration from murine wounds. As a result of this work, the laboratory now has at hand detailed protocols leading to the isolation of high purity RNA from wound macrophages. Additional work was conducted in collaboration with Dr. Minsoo Kim, a former faculty member in the Division of Surgical Research. Together, they were able to acquire real time images of the respiratory burst of human neutrophils to correlate such burst with the expression of apoptotic markers. Experiments were also performed to allow the laboratory to switch from the use of anti-Gr1 Ab to the more specific 1A8 anti-Ly6-G Ab for the induction of neutropenia and of neutropenic wounds in mice. Results were presented in part at the New England Surgical Society meeting and at the Academic Surgical Congress 1st Annual Meeting in San Diego, CA.
Publications:
Daley JM, Thomay AA, Connolly MD, Reichner JS, Albina JE. Use of Ly6G-specific monoclonal antibody to deplete neutrophils in mice. J Leukoc Biol. 83(1):64-70, 2008
Harrington DT, Connolly MD, Biffl WL, Majercik SD, Cioffi WG. Transfer times to definitive care facilities are too long: a consequence of an immature trauma system. Ann Surg. 241(6):961-6, 2005
Current Location:
After his time on the Training Grant, Dr. Connolly completed his 5 years as a general surgery resident and is currently in a Trauma/Critical Care Fellowship at Rhode Island Hospital.
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PGY 2 Resident Department of Surgery Rhode Island Hospital Term: 7/2005 - 6/2007 |
Education:
2003 - 2007; Surgical Residency, Brown University, Providence, RI
2003 - M.D., Wayne State University, Detroit, MI
1999 - B.S., Biopsychology, University of Michigan, Ann Arbor, MI
Lab Research:
Dr. Swan worked in Dr. Alfred Ayala's lab where he researched the contribution of macrophage clearance of apoptotic cells to the pathophysiology of sepsis. A hallmark of sepsis in animal models and human studies is widespread immune cell apoptosis, which has been linked to increased morbidity and mortality. Macrophage phagocytosis of apoptotic immune cells leads to release of anti-inflammatory cytokines as a physiologic mechanism for controlling inflammation; however, in the setting of massive immune cell apoptosis as seen in sepsis, this process may contribute to the immunosuppressed state seen in septic patients.
Publications:
Chiang C, Swan RZ, Grachtchouk M, Bolinger M, Litingtung Y, Robertson EK, Cooper MK, Gaffield W, Westphal H, Beachy PA, and Dlugosz AA. Essential Role for sonic hedgehog during hair follicle morphogenesis. Dev Biol 1999; 205: 1-9.
Swan R, Miner T. Current role of surgical therapy in gastric cancer. World J Gastroenterol 2006; 12 (3): 372-379.
Wesche-Soldato DE, Swan R, Chung CS, Ayala A. The apoptotic pathway as a therapeutic target in sepsis. Curr Drug Targets 2007; 8(4), 493-500.
Swan R, Chung CS, Albina J, Cioffi W, Perl M, Ayala A. Polymicrobial sepsis enhances clearance of apoptotic immune cells by splenic macrophages. Surgery 2007; 142: 253-261.
Delano MJ, Scumpia PO, Weinstein JS, Coco D, Nagaraj S, Kelly-Scumpia KM, O’Malley KA, Wynn J, Antonenko S, Al-Quran S, Swan R, Chung CS, Atkinson MA, Ramphal R, Gabrilovich DI, Reeves WH, Ayala A, Phillips J, LaFace D, Hayworth P, Clare-Salzler M, Moldawar LL. MyD88 dependent expansion of an immature Gr-1+CD11b+ induces T-cell suppression and TH2 polarization in sepsis. J Exp Med 2007; 204(6): 1463-74.
Ayala A, Perl M, Venet F, Lomas-Neira J, Swan R, Chung CS. Apoptosis in sepsis: mechanisms, clinical impact and potential therapeutic targets.
Curr Pharm Des. 2008;14(19):1853-9. Review.
Huang X, Venet F, Wang YL, Lepape A, Yuan Z, Chen Y, Swan R, Kherouf H, Monneret G, Chung CS, Ayala A. PD-1 expression by macrophages plays a pathologic role in altering microbial clearance and the innate inflammatory response to sepsis. Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6303-8. Epub 2009 Mar 30.
Published Abstracts:
Swan RZ, Grachtchouk M, Robertson EK, Cooper MK, Beachy PA, and Dlugosz AA. Cyclophosphamide inhibits sonic hedgehog signaling and blocks morphogenesis of vibrissa follicle explants. J Invest Dermatol 1999; 112: 16.
Iannitti D, Soares G, Swan R, Dubel G, Safran H, Rathore R. A phase I study of hepatic arterial infusion of oxaliplatin in advanced hepatocellular cancer. HPB 2006; 8 (Suppl. 1): 39.
Swan R, Khan A, Simon C, Dupuy D, Soares G, Safran H, Iannitti D. Transarterial chemoembolization followed by radiofrequency ablation for hepatocellular carcinoma greater than 4cm in diameter. HPB 2006; 8 (Suppl.1): 63-64.
Swan R, Chung CS, Ayala A. Sepsis differentially effects macrophage clearance of apoptotic thymocytes. Shock 2006; 25 (Suppl. 1): 77-78.
Current Location:
Dr. Swan is currently at St. Luke’s-Roosevelt Hospital Center, Department of Surgery Residency Program, New York, NY.
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3rd Year Postdoctoral Research Associate Division of Surgical Research Rhode Island Hospital Term: 7/2006 - 9/2008 * |
Education:
2003 - Ph.D., Integrative Physiology, Univ. of Colorado, Boulder, CO
2000 - M.S., Kinesiology and Applied Physiology, Univ. of Colorado, Boulder, CO
1997 - M.A., History and Museum Studies, SUNY, Oneonta, NY
1993 - B.A., Anthropology, Tufts University, Medford, MA
Lab Research:
Dr. Elphick worked in Dr. Alfred Ayala's lab where she explored the effects of activated protein C on leukocyte migration during sepsis in both humans and an animal model. Sepsis, also known as systemic inflammatory response syndrome (SIRS), is a serious medical condition caused by inflammatory response which leads to secretion of pro- and anti-inflammatory cytokines, activation and migration of leukocytes, activation of coagulation and inhibition of fibrinolysis, and increased apoptosis. Severe sepsis, defined as sepsis associated with acute organ dysfunction, is an increasing cause of morbidity and mortality among children and adults, and has been one of the most significant challenges in critical care. Recently, a recombinant form of activated protein C (rhAPC or drotrecogin alfa activated; commercially as "Xigris©") was approved by FDA for the treatment severe sepsis and a high risk of mortality. Despite the ability of rhAPC to improve survival among patients with severe sepsis, the mechanisms by which APC protects septic patients remain largely unknown.
Although initial hypotheses focused on antithrombotic and profibrinolytic functions of APC in sepsis, other agents that also have potent effects on such pathways did not demonstrate the same clinical benefit in severe sepsis as was seen with rhAPC. Excessive sequestration and infiltration of neutrophils through dysregulated cell surface adhesion molecule, integrin, is another known factor that contributes to tissue injury and the pathophysiology of sepsis. Dr. Elphick's specific area of interest was changes in integrin expression and activation during sepsis, and how APC regulates integrin mediated neutrophil migration and how it impacts disease outcome.
Publications, Abstracts & Presentations:
Elphick, G.F., Greenwood, B.N., Campisi, J., Fleshner, M. Increased serum nIgM in voluntarily physically active rats: a potential role for B-1 cells. J. Appl. Physiol. 94(2):660-7, 2003.
Elphick, G.F., Wieseler-Frank, J., Greenwood, B.N., Campisi, J., Fleshner, M. B-1 cell (CD5+/CD11b+) numbers and nIgM levels are elevated in physically active vs. sedentary rats. J. Appl. Physiol. 95(1):199-206, 2003.
Elphick, G.F., Querbes, W., Jordan, J.A., Gee, G.V., Eash, S., Manley, K., Dugan, A., Stanifer, M., Bhatnagar, A., Kroeze, W.K., Roth, B.L., Atwood, W.J. The human polyomavirus, JCV, uses serotonin receptors to infect cells. Science 306(5700):1380-3, 2004.
Nickerson, M., Elphick, G.F., Campisi, J., Greenwood, B.N., Fleshner, M. Physical activity alters the brain Hsp72 and IL-1beta responses to peripheral E. coli challenge. Am. J. Physiol. Regul. Integr. Comp. Physiol. 289(6):R1665-74, 2005.
Elphick G.F., Sarangi PP, Hyun YM, Hollenbaugh JA, Ayala A, Biffl WL, Chung HL, Rezaie AR, McGrath JL, Topham DJ, Reichner JS, Kim M. Recombinant human activated protein C inhibits integrin-mediated neutrophil migration.
Blood. 2009 Apr 23;113(17):4078-85. Epub 2009 Feb 24.
Current Location:
Gwen is continuing her research in Dr. Alfred Ayala's lab at Rhode Island Hospital.
*Term extended due to a 3-month maternity leave
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PGY 2 Surgical Resident Department of Surgery Rhode Island Hospital Term: 7/2007 - 6/2009 |
Education:
2005 - Present; Surgical Resident, Rhode Island Hospital, Providence, RI
2005 - M.D., University of Maryland School of Medicine, Baltimore, MD
2001 - B.A., cum laude, Physiology and Neurobiology; University of Maryland College Park, MD
Lab Research:
Dr. Johnstone trained in Dr. Jonathan Reichner's lab researching the requirements for VAV guanine nucleotide exchange factors in phagocytosis of zymosan and apoptotic bodies and the effect of sepsis on VAV-mediated host defense.
Neutrophils, macrophages and dendritic cells are commonly referred to as “professional phagocytes” in homage to their highly developed capacity to perform this fundamental function in host defense and tissue repair. Under no condition is this protective mechanism under greater challenge then during polymicrobial sepsis, in which overwhelming numbers of opsonized and nonopsonized microbes and apoptotic bodies from dying phagocytes provide surfeit sources of ingestible material for clearance by these specialized cells. Phagocytes express a number of phagocytic receptors including Fc receptors, Beta2 leukocyte integrins, dectin-1 and several receptors for apoptotic bodies that, together, allow for efficient recognition and clearance of these organisms.
In a collaborative effort with the laboratory of Dr. Joan Brugge, Chair Cell Biology, Brigham and Womens Hospital, Harvard Medical School, Dr. Johnstone strived to determine the role of VAV guanine nucleotide exchange factors in the ability of murine macrophages and neutrophils to phagocytose apoptotic bodies and zymosan. This is a direct extension of recent reports from Dr. Brugge’s laboratory showing that VAV signaling is required for integrin, but not Fc-mediated phagocytosis (Hall et al., “Requirements for VAV guanine nucleotide exchange factors and Rho GTPases in FcgR- and complement-mediated phagocytosis” Immunity 24: 305,2006). This paradigm-shifting report highlighted the fact that selective regulation exists among the different phagocytic receptors. This will be extended to determine the role of VAV in other receptor-mediated phagocytic pathways, including those for internalization of apoptotic bodies and yeast particles (zymosan) to provide a thorough analysis of the selective role of VAV in phagocytosis. Dr. Brugge’s laboratory provided mice that were genetically deficient in VAV along with technical recommendations that allowed Dr. Johnstone to provide a seamless extension of their prior reports.
More importantly, Dr. Johnstone's goal was to determine the effects of sepsis on each phagocytic pathway with the consideration that they are differentially regulated and may not all be affected by sepsis in the same way. This was done in collaboration with Dr. Ayala and furthered the work of a previous Trauma Training resident, Dr. Ryan Swan, who found that sepsis impedes the uptake of apoptotic bodies by murine macrophages.
Publications, Abstracts & Presentations:
Johnstone, J.K., Morin, N.A, Cioffi, W.G., Albina, J.E., and Reichner, J.S. VAV guanine nucleotide exchange factor is required for Dectin-1 mediated phagocytosis. Presented at the 94th Annual Clinical Congress, Committee for the Forum on Fundamental Surgical Problems of the American College of Surgeons, San Francisco, CA, October 2008.
Current Location:
Jill is completing her training in the general surgery resident program at Rhode Island Hospital.
