Barbara Murphy, MD
- DEAN FOR CLINICAL INTEGRATION AND POPULATION HEALTH
- PROFESSOR AND SYSTEM CHAIR | Medicine, Nephrology
Specialties:Kidney / Pancreas Transplantation, Nephrology
Barbara Murphy, MD is the Murray M. Rosenberg Professor of Medicine, Chair of the Department of Medicine for the Mount Sinai Health System and Dean for Clinical Integration and Population Health. Her area of interest is transplant immunology, focusing on genomics in determining outcomes in transplantation and the Immunomodulatory role of MHC derived peptides.
Dr. Murphy earned her M.B. B.A.O. B.Ch. from The Royal College of Surgeons in Ireland and went on to do an internship at Beaumont Hospital in Dublin. She completed a residency rotation at Beaumont Hospital followed by a fellowship in Clinical Nephrology also at Beaumont Hospital. Dr. Murphy completed her postdoctoral training with a fellowship in Nephrology at Brigham and Women's Hospital, Harvard Medical School. As part of this she trained in transplant immunology at the Laboratory of Immunogenetics and Transplantation, Renal Division, Brigham and Women's Hospital, Harvard Medical School. Among her many honors, Dr. Murphy was awarded the Young Investigator Award in Basic Science by the American Society of Transplantation in 2003. In 2005, Dr. Murphy was awarded the Irene and Dr. Arthur M. Fishberg Professor of Medicine at The Mount Sinai Hospital. Then, in 2011, she was named Nephrologist of the Year by the American Kidney Fund.
Dr. Murphy belongs to a number of professional societies including the American Society of Transplantation and the American Society of Nephrology. Among her numerous achievements she has had many leadership roles at a national level, including being a member of the Board of the American Society of Transplantation, the Executive Committee of the American Transplant Congress, and Chair of Education Committee of the American Society of Transplantation. Most recently, she served as the president of the American Society of Transplantation and is currently the Co-Chair of the American Society of Transplantation Public Policy. In these positions, Dr. Murphy aims to directly impact patient care and access to healthcare, specifically, advocating for long-term coverage for immunosuppression.
Dr. Murphy's research has focused on two major areas. Having demonstrated that MHC class II peptides derived from non-polymorphic regions may inhibit the alloimmune response in vitro and in vivo, Dr. Murphy is currently investigating their mechanisms of action and their ability to prolong allograft survival in vivo. Dr. Murphy is also the PI of a large multicenter NIH study investigating the role of genomic to predict the development of chronic allograft nephropathy. She was a co-investigator on the recent the landmark study investigating outcomes in HIV positive patients that receive a solid organ transplant.
Multi-Disciplinary Training AreaImmunology [IMM]
MB BAO BCh, The Royal College of Surgeons
MD, Royal College of Surgeons-Ireland
MRCPI, The Royal College of Physicians
FRCPI, The Royal College of Physicians
Internship, Internal Medicine, Beaumont Hospital
Fellowship, Nephrology, Beaumont Hospital
Fellowship, Nephrology-Renal, Brigham and Women's Hospital, Harvard Medical School
Executive Committee and Chair 2007
Irene and Dr. Arthur M. Fishberg Professor of Medicine
Young Investigator Award
Immunosuppressive mediated Action of MHC class II-derived Peptides
Synthetic peptides derived from highly conserved regions of the MHC class I and II sequences can inhibit the immune response in vitro and in vivo through a variety of mechanisms including the inhibition of signal transduction and cell cycle progression. We have shown that peptides derived from a conserved region of the MHC class II alpha chain inhibit T cell proliferation in an allele and species non-specific manner and that they prevent generation of cytotoxic T cells. One of these peptides, HLA-DQA1, is the most effective requiring lower doses for maximal effect compared to other peptides. HLA-DQA1 inhibits the direct and indirect pathway of allorecognition via induction of non-classical apoptotic pathways in antigen presenting cells (APC), and also inhibits proliferation to autoantigen in vitro. The effect of HLA-DQA1 is sequence specific and when injected in conjunction with allogeneic cells at the stage of initial priming in a DTH model, completely prevents the DTH response. Furthermore, if HLA-DQA1 is co-injected with cells at the time of rechallenge, following initial priming, again the DTH response showing that HLA-DQA1 prevents both the priming of allogeneic T cells, and the response of primed allogeneic T cells. Skin allograft survival in mice treated with a combination of HLA-DQA1 peptide and a subtherapeutic dose of Rapamycin was significantly prolonged as compared to controls in a stringent model of acute rejection showing that MHC class II derived peptides act synergistically with Rapamycin to effectively prolong allograft survival in vivo. Current studies focus on determining the binding site and mechanism of action of these immunomodulatory MHC derived peptides and their ability to alter or prevent allograft rejection and autoimmune diseases in animal models.
Genetic Variability and Outcomes in Transplantation
Organ transplantation results in increased life expectancy and lifestyle advantages as compared to all other modalities of kidney replacement therapy. Despite a marked improvement in rejection rates over the last decade, the improvement in long-term allograft survival remains modest. Recent advances from the Human Genome Project have identified numerous regions of genetic variability, both single-nucleotide polymorphisms (SNP's) and microsatellites regions, within genes relevant to transplantation. We have studied polymorphisms in chemokines and their receptor and costimulatory molecules and demonstrated three gene polymorphisms in CTLA-4 including one microsatellite dinucleotide repeat in the 3' untranslated region (3'-UTR) of the final exon (+642 (AT)n), and two SNP's located in the promoter (-318 C/T) and the first exon (+49 A/G) associated with functional effects and the incidence of autoimmune diseases. We have found an association with the (AT)92 and (AT)94 alleles of the +642 (AT)n microsatellite and acute rejection in both liver and kidney recipients. Analysis of CTLA-4 +49A/G demonstrated no association with acute rejection in either kidneys or livers. We have now extended this analysis to include the CTLA4 -318C/T and CD28 +17T/C SNP's for acute rejection and allograft survival. Homozygosity for the G allele of CTLA4 +49A/G significantly reduced 5 and 10-year graft survival, while the CTLA-4 +642(AT)n alleles associated with acute rejection (92, 94 and 100bp) were also associated with decreased graft survival and occurred more frequently in African American. Studies now focus on the relationship between haplotypes, graft survival and acute rejection. These studies form the basis for a larger prospective study in transplant recipients.
- Genomics of Chronic Renal Allograft Rejection
The purposes of this study are to determine the role of cell and antibody mediated responses in chronic rejection, to determine the gene expression profile associated with the development of chronic rejection, and to determine whether polymorphic variants of specific immunolog...
Murphy B, Auchincloss H, Carpenter CB, Sayegh MH. T cell recognition of xeno-MHC peptides during concordant xenograft rejection. Transplantation 1996 Apr; 61(8).
Murphy B, Waaga AM, Carpenter CB, Sayegh MH. Inhibition of the alloimmune response by synthetic peptides derived from highly conserved regions of class II MHC alpha chain. Journal for 12th International Histocompatibility Conference 1996 June;.
Murphy B, Kim KS, Buelow R, Sayegh MH, Hancock WW. Synthetic MHC class I peptide prolongs cardiac survival and attenuates transplant arteriosclerosis in the Lewis-->Fischer 344 model of chronic allograft rejection. Transplantation 1997 Jul; 64(1).
Murphy B, Magee CC, Alexander SI, Waaga AM, Snoeck HW, Vella JP, Carpenter CB, Sayegh MH. Inhibition of allorecognition by a human class II MHC-derived peptide through the induction of apoptosis. The Journal of clinical investigation 1999 Mar; 103(6).
Slavcheva E, Albanis E, Jiao Q, Tran H, Bodian C, Knight R, Milford E, Schiano T, Tomer Y, Murphy B. Cytotoxic T-lymphocyte antigen 4 gene polymorphisms and susceptibility to acute allograft rejection. Transplantation 2001 Sep; 72(5).
Schröppel B, Fischereder M, Ashkar R, Lin M, Krämer BK, Mardera B, Schiano T, Murphy B. The impact of polymorphisms in chemokine and chemokine receptors on outcomes in liver transplantation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2002 Aug; 2(7).
Schröppel B, Fischereder M, Lin M, Marder B, Schiano T, Krämer BK, Murphy B. Analysis of gene polymorphisms in the regulatory region of MCP-1, RANTES, and CCR5 in liver transplant recipients. Journal of clinical immunology 2002 Nov; 22(6).
Marder BA, Schröppel B, Lin M, Schiano T, Parekh R, Tomer Y, Murphy B. The impact of costimulatory molecule gene polymorphisms on clinical outcomes in liver transplantation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2003 Apr; 3(4).
Murphy B, Yu J, Jiao Q, Lin M, Chitnis T, Sayegh MH. A novel mechanism for the immunomodulatory functions of class II MHC-derived peptides. Journal of the American Society of Nephrology : JASN 2003 Apr; 14(4).
Schröppel B, Zhang N, Chen P, Zang W, Chen D, Hudkins KL, Kuziel WA, Sung R, Bromberg JS, Murphy B. Differential expression of chemokines and chemokine receptors in murine islet allografts: the role of CCR2 and CCR5 signaling pathways. Journal of the American Society of Nephrology : JASN 2004 Jul; 15(7).
Schröppel B, Zhang N, Chen P, Chen D, Bromberg JS, Murphy B. Role of donor-derived monocyte chemoattractant protein-1 in murine islet transplantation. Journal of the American Society of Nephrology : JASN 2005 Feb; 16(2).
Zang W, Kalache S, Lin M, Schroppel B, Murphy B. MHC Class II-mediated apoptosis by a nonpolymorphic MHC Class II peptide proceeds by activation of protein kinase C. Journal of the American Society of Nephrology : JASN 2005 Dec; 16(12).
Gallon L, Akalin E, Lynch P, Rothberg L, Parker M, Schiano T, Abecassis M, Murphy B. ACE gene D/D genotype as a risk factor for chronic nephrotoxicity from calcineurin inhibitors in liver transplant recipients. Transplantation 2006 Feb; 81(3).
Ommen ES, Winston JA, Murphy B. Medical risks in living kidney donors: absence of proof is not proof of absence. Clinical journal of the American Society of Nephrology : CJASN 2006 Jul; 1(4).
Ommen ES, Schröppel B, Kim JY, Gaspard G, Akalin E, de Boccardo G, Sehgal V, Lipkowitz M, Murphy B. Routine use of ambulatory blood pressure monitoring in potential living kidney donors. Clinical journal of the American Society of Nephrology : CJASN 2007 Sep; 2(5).
Akalin E, Dinavahi R, Dikman S, de Boccardo G, Friedlander R, Schroppel B, Sehgal V, Bromberg JS, Heeger P, Murphy B. Transplant glomerulopathy may occur in the absence of donor-specific antibody and C4d staining. Clinical journal of the American Society of Nephrology : CJASN 2007 Nov; 2(6).
Roland ME, Barin B, Carlson L, Frassetto LA, Terrault NA, Hirose R, Freise CE, Benet LZ, Ascher NL, Roberts JP, Murphy B, Keller MJ, Olthoff KM, Blumberg EA, Brayman KL, Bartlett ST, Davis CE, McCune JM, Bredt BM, Stablein DM, Stock PG. HIV-infected liver and kidney transplant recipients: 1- and 3-year outcomes. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2008 Feb; 8(2).
Zang W, Lin M, Kalache S, Zhang N, Krüger B, Waaga-Gasser AM, Grimm M, Hancock W, Heeger P, Schröppel B, Murphy B. Inhibition of the alloimmune response through the generation of regulatory T cells by a MHC class II-derived peptide. Journal of immunology (Baltimore, Md. : 1950) 2008 Dec; 181(11).
Krüger B, Krick S, Dhillon N, Lerner SM, Ames S, Bromberg JS, Lin M, Walsh L, Vella J, Fischereder M, Krämer BK, Colvin RB, Heeger PS, Murphy BT, Schröppel B. Donor Toll-like receptor 4 contributes to ischemia and reperfusion injury following human kidney transplantation. Proceedings of the National Academy of Sciences of the United States of America 2009 Mar; 106(9).
Sawinski D, Wyatt CM, Casagrande L, Myoung P, Bijan I, Akalin E, Schröppel B, DeBoccardo G, Sehgal V, Dinavahi R, Lerner S, Ames S, Bromberg J, Huprikar S, Keller M, Murphy B. Factors associated with failure to list HIV-positive kidney transplant candidates. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2009 Jun; 9(6).
Dhillon N, Walsh L, Krüger B, Mehrotra A, Ward SC, Godbold J, Radwan M, Schiano T, Murphy B, Schröppel B. Complement component C3 allotypes and outcomes in liver transplantation. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 2010 Feb; 16(2).
Dhillon N, Walsh L, Krüger B, Ward SC, Godbold JH, Radwan M, Schiano T, Murphy BT, Schröppel B. A single nucleotide polymorphism of Toll-like receptor 4 identifies the risk of developing graft failure after liver transplantation. Journal of hepatology 2010 Jul; 53(1).
Humar A, Morris M, Blumberg E, Freeman R, Preiksaitis J, Kiberd B, Schweitzer E, Ganz S, Caliendo A, Orlowski JP, Wilson B, Kotton C, Michaels M, Kleinman S, Geier S, Murphy B, Green M, Levi M, Knoll G, Segev D, Brubaker S, Hasz R, Lebovitz DJ, Mulligan D, O'Connor K, Pruett T, Mozes M, Lee I, Delmonico F, Fischer S. Nucleic acid testing (NAT) of organ donors: is the 'best' test the right test? A consensus conference report. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2010 Apr; 10(4).
Gurkan S, Luan Y, Dhillon N, Allam SR, Montague T, Bromberg JS, Ames S, Lerner S, Ebcioglu Z, Nair V, Dinavahi R, Sehgal V, Heeger P, Schroppel B, Murphy B. Immune reconstitution following rabbit antithymocyte globulin. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2010 Sep; 10(9).
Evans RW, Applegate WH, Briscoe DM, Cohen DJ, Rorick CC, Murphy BT, Madsen JC. Cost-related immunosuppressive medication nonadherence among kidney transplant recipients. Clinical journal of the American Society of Nephrology : CJASN 2010 Dec; 5(12).
Stock PG, Barin B, Murphy B, Hanto D, Diego JM, Light J, Davis C, Blumberg E, Simon D, Subramanian A, Millis JM, Lyon GM, Brayman K, Slakey D, Shapiro R, Melancon J, Jacobson JM, Stosor V, Olson JL, Stablein DM, Roland ME. Outcomes of kidney transplantation in HIV-infected recipients. The New England journal of medicine 2010 Nov; 363(21).