- DEAN FOR CLINICAL INTEGRATION AND POPULATION HEALTH
- PROFESSOR AND SYSTEM CHAIR | Medicine, Nephrology
- Kidney / Pancreas Transplantation
- Hospital Affiliation
- The Mount Sinai Hospital
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 the use of high throughput genomic technologies as a means to understand the immune mechanisms that lead to graft injury and loss, with the aim of identifying gene expression profiles and or genetic variants that may be used to predict those at greatest risk.
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. She received the distinguished Jacobi Medallion in 2014. She also received an honorary degree from University College, Dublin, Ireland. In 2016, Dr. Murphy was honored by The Annual Irish America Healthcare & Life Science 50.
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 held 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. In 2016, The American Society of Nephrology elected Dr. Murphy as its newest Councilor. 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 is the Principle Investigator of a study, the Genomics of Chronic Renal Allograft Rejection, (GoCar), which aims to investigate the mechanisms leading to the development of transplant glomerulopathy, chronic arteriopathy funded through the NIH/NIAID Genomics Consortium in Transplantation. The GoCar study, recently published in The Lancet, examines gene expression profiles associated with the development of chronic rejection using microarray on protocol biopsies performed over two years following transplantation. In addition, a larger cohort of donor and recipient pairs are being enrolled to identify polymorphic variants of specific immunological genes which confer susceptibility to chronic rejection and the development of donor specific antibodies.
Dr. Murphy's Lab also investigated a systems biology approach to the identification of genetic drivers of fibrosis in the allograft and the potential application to native kidney. Through this mechanism they have identified several novel mediators of fibrosis which are being investigated further in humans and animal models. SHROOM3 is one such gene. An intronic SNP in SHROOM3 increases expression of SHROOM3 and drives fibrosis in human allograft recipients and murine models of CKD. Her research was published in The Journal of Clinical Investigation.
To read more about Dr. Murphy's research, please visit The Murphy Lab.
Multi-Disciplinary Training Area
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
Brigham and Women's Hospital, Harvard Medical School
The American Society of Nephrology
The Annual Irish America Healthcare & Life Sciences 50
Royal College of Physicians London
Mount Sinai Health System
Elected Fellow of the American College of Physicians
American Society of Transplantation
Executive Committee and Chair 2007
AITRC Study Section
American Society of Transplantation
Irene and Dr. Arthur M. Fishberg Professor of Medicine
Young Investigator Award
American Society of Transplantation
American Society of Transplantation
American Society of Nephrology
Transplant Advisory Group
American Society of Nephrology
National Institute of Health
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.
The Genomics of Chronic Allograft Rejection (GoCAR)
This study aims to investigate the mechanisms leading to the development of transplant glomerulopathy, chronic arteriopathy funded through the NIH/NIAID Genomics Consortium in Transplantation. The study examines the contribution of the direct and indirect pathways of allorecognition, and the development of de novo donor specific antibodies to this pathologic finding in a large prospective group of renal transplant recipients. The studies is examining the gene expression profile associated with the development of chronic rejection using microarray on protocol biopsies performed over two years following transplantation. In addition, a larger cohort of donor and recipient pairs are being enrolled to identify polymorphic variants of specific immunological genes which confer susceptibility to chronic rejection and the development of donor specific antibodies.
Patients have been enrolled in 5 clinical sites including Mount Sinai, Westmead Hospital Sydney, University Wisconsin – Madison Medical Center, University of Michigan Medical Center, Ann Arbor, and Northwestern Medical Center. The findings of this study will lead to important insights into the pathologic mechanisms mediating chronic allograft loss. Initial finding suggest that differential gene expression on normal 3 month protocol biopsies may be potentially used to immunologically stratify transplant recipients.
Researchers Identify Genes That Predict Damage in Donated Kidneys
From The Lancet: Biopsy transcriptome expression profiling to identify kidney transplants at risk of chronic injury: a multicentre, prospective study
Risk factor for Renal Allograft Fibrosis
A systems biology approach to the identification of genetic drivers of fibrosis in the allograft and the potential application to native kidney. Through this mechanism we have identified several novel mediators of fibrosis which are being investigated further in humans and animal models. SHROOM3 is one such gene. An intronic SNP in SHROOM3 increases expression of SHROOM3 and drives fibrosis in human allograft recipients and murine models of CKD.
From JCI: Intronic locus determines SHROOM3 expression and potentiates renal allograft fibrosis
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 immunologica...
Li L, Greene I, Readhead B, Menon M, Kidd B, Uzilov A, Wei C, Philippe N, Schroppel B, He J, Chen R, Dudley J, Murphy B. Novel Therapeutics Identification for Fibrosis in Renal Allograft Using Integrative Informatics Approach.. Sci Rep. 2017 Jan; 4(7): 39487.
Wei C, Li L, Menon M, Zhang W, Fu J, Kidd B, Keung K, Woytovich C, Greene I, Xiao W, Salem F, Yi Z, He J, Dudley J, Murphy B. Genomic Analysis of Kidney Allograft Injury Identifies Hematopoietic Cell Kinase as a Key Driver of Renal Fibrosis.. J Am Soc Nephrol. 2017 May; 28(5): 1385-1393.
O'Connell P, Zhang W, Menon M, Yi Z, Schroppel B, Gallon L, Luan Y, Rosales I, Ge Y, Losic B, Xi C, Woytovich C, Keung K, Wei C, Greene I, Overbey J, Bagiella E, Najafian N, Samaniego M, Djamali A, Alexander S, Nankivell B, Chapman J, Smith R, Colvin R, Murphy B. Biopsy transcriptome expression profiling to identify kidney transplants at risk of chronic injury: a multicentre, prospective study. The Lancet 2016 July; 388(10048): 983-993.
Menon M, Chuag P, Li Z, Wei C, Zhang W, Luan Y, Yi Z, Xiong H, Woytovich C, Greene I, Overbey J, Rosales I, Bagiella E, Chen R, Ma M, Li L, Ding W, Djamali A, Saminego M, O'Connell P, Gallon L, Colvin R, Schroppel B, He J, Murphy B. Intronic locus determines SHROOM3 expression and potentiates renal allograft fibrosis. J Clin Invest. 2015 January; 125(1): 208-221.
Luan Y, Mosheir E, Menon M, Wilson D, Woytovich C, Ochando J, Murphy B. Monocytic myeloid-derived suppressor cells accumulate in renal transplant patients and mediate CD4(+) Foxp3(+) Treg expansion.. Am J Transplant. 2013 Dec.; 13(12): 3123-31.
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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, 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, Auchincloss H, Carpenter CB, Sayegh MH. T cell recognition of xeno-MHC peptides during concordant xenograft rejection. Transplantation 1996 Apr; 61(8).
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Below are financial relationships with industry reported by Dr. Murphy during 2017 and/or 2018. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
Other activities: Examples include, but are not limited to, committee participation, data safety monitoring board (DSMB) membership
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