Specialty	Renal Transplantation
Subspecialty	Nephrology
Clinical Interests	HIV
	Kidney Biopsy
	Kidney Dialysis
	Kidney Disease
	Kidney Disorders
	Kidney Transplant
	Kidney/Pancreas Transplant
	Transplant Related Infections
	Transplantation
Languages	English
Gender	Female
E-mail	barbara.murphy@mssm.edu
Education and Training	MD, Royal College of Surgeons-Ireland
	F.R.C.P.I., The Royal College of Physicians
	M.R.C.P.I., The Royal College of Physicians
	MB BAO BCh, The Royal College of Surgeons
	Internship, Internal Medicine, Beaumont Hospital
	Fellowship, Nephrology-Renal, Brigham and Women's Hospital
	Fellowship, Nephrology, Beaumont Hospital
Awards	2007 President Elect American Society of Transplantation
	2005 - 2007 Executive Committee and Chair 2007 ATC
	2004 Member AITRC Study Section NIAID/NIH
	2004 Irene and Dr. Arthur M. Fishberg Professor of Medicine
	2004 - 2007 Councilor-at-Large American Society of Transplantation
	2003 Young Investigator Award American Society of Transplantation Basic Science
	2003 - 2005 Chair Transplant Advisory Group American Society of Nephrology
	2003 - 2004 Chair Education Committee American Society of Transplantation
	2001 Member Program Committee American Society of Nephrology
	1997 - 2001 KO8 Award Principle Investigator National Institute of Health

Dr. Murphy currently serves as the Irene and Arthur M. Fishberg Professor of Medicine. Her area of interest is transplant immunology, focusing on the Immunomodulatory role of MHC derived peptides; and the influence of genetic polymorphisms in determining outcomes in transplantation.

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.

Dr. Murphy belongs to a number of professional societies including the American Society of Transplantation and the American Society of Nephrology. Among her many leadership roles at a national level, Dr. Murphy is on the Editorial Board for the Journal of American Society of Nephrology, the Board of the American Society of Transplantation, the Executive Committee of the American Transplant Congress, and the Education Committee of the American Society of Nephrology.

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 investigating the association between genetic polymorphisms in key immunoregulatory molecules and outcomes in liver and kidney transplant recipients. These outcomes include acute rejection and long-term survival of the transplanted organ.

Curriculum Vitae: http://www.mountsinai.org/supporting-files/cv/murp...

Education and Training	MD, Royal College of Surgeons-Ireland
	F.R.C.P.I., The Royal College of Physicians
	M.R.C.P.I., The Royal College of Physicians
	MB BAO BCh, The Royal College of Surgeons
	Internship, Internal Medicine, Beaumont Hospital
	Fellowship, Nephrology-Renal, Brigham and Women's Hospital
	Fellowship, Nephrology, Beaumont Hospital

Specialty	Renal Transplantation
Subspecialty	Nephrology
Clinical Interests	HIV
	Kidney Biopsy
	Kidney Dialysis
	Kidney Disease
	Kidney Disorders
	Kidney Transplant
	Kidney/Pancreas Transplant
	Transplant Related Infections
	Transplantation
Languages	English

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.

Zang W, Kalache S, Hancock MW, Waaga-Gasser AM, Grimm M, Zhang N. Inhibition of the Alloimmune Response through the induction of Regulatory T cells by an MHC class II Peptide. Jour Immunol 2007;.

Ommen L, Murphy B, Lipkowitz M. Routine Ambulatory Blood Pressure Monitoring in Potenital Living Kidney Donors. CJASN;.

Ommen L, Murphy B, Winston J. Medical risks in living kidney donors: Absence of proof is not proof of absence. CJASN 2006; 1: 885-895.

Linden E, Restrepo D, , Murphy B, Huprikar S, Dikman S. Aspergillus Infection Limited to Renal Allograft: Case Report and Review of Literature. Transpl Infect Dis. 2006; 8(3): 177-181.

Wyatt CM, Dikman S, Seghal V, Akalin E, Bromberg JS, Ames S, Murphy BT. Chronic Organizing Microangiopathy in a Renal Transplant Recipient. Nephrology, Dialysis, and Transplantation 2005; 20: 1734-1737.

Gallon L, Akalin E, Lynch P, Murphy B, Parker M, Schiano T, Abecassis M, Rothberg L. Angiotensin converting enzyme (ACE) gene D/D polymorphism as a determinant for the development of chronic nephrotoxicity from Calcineurin inhibitors in liver transplant recipients. Transplantation 2006; 81: 453-468.

Zang W, Kalanche S, Lin M, Schroppel B, Murphy B. MHC Class II Mediated Apoptosis by a Non-Polymorphic MHC Class II Peptide Proceeds by Activation of Protein Kinase C. Journal Am Soc Nephrol 2005; 16: 3661-3668.

Schroppel B, Zhang N, Chen P, Chen D, Bromberg JS, Murphy B. Role of donor-derived monocyte chemoattractant protein-1 in murine islet transplantation. J Am Soc Nephrol 2005 Feb; 16(2): 444-51.

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. J Am Soc Nephrol 2005 Dec; 16(12): 3661-8.

Schroppel 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. J Am Soc Nephrol 2004 Jul; 15(7): 1853-61.