Information

Related Research Units

Nephrology Research
Briscoe Lab Research

Research Overview

Dr. Briscoe’s research focuses on transplantation immunlogy and mechanisms underlying in evolution of chronic allograft rejection. He has held several NIH R01 grants to support discovery-based research and he has advanced biomarker development as a critical transformative care initiative.

Research Background

Dr. David Briscoe is a Professor of Pediatrics at Harvard Medical School and the Casey Lee Ball Chair in Transplantation at Boston Children's Hospital. He trained in Pediatrics, Nephrology and transplantation immunology and directs a research program focused on the understanding of chronic allograft rejection with a goal to enhance long-term outcomes following solid organ transplantation.

Dr. Briscoe earned his medical degree at the Royal College of Surgeons in Ireland and performed his initial residency training in General Medicine and Pediatrics in Dublin. He also completed Pediatric Residency training at the University of Colorado Health Sciences Center in Denver, Colorado, and a postdoctoral fellowship in Pediatric Nephrology at Boston Children’s Hospital and Harvard Medical School. Among several honors, Dr. Briscoe was awarded a Young Investigator Award and the Basic Science Investigator Award of the American Society of Transplantation. He was also elected to the national honors society, the American Society of Clinical Investigation. In 2008, Dr. Briscoe became the Principal Investigator of a T32 training program grant, which he has sustained and is currently funded through 2025.. In 2013, he was appointed Director of the Transplant Research Program at Boston Children’s Hospital, and in 2015, he became the first incumbent Casey Lee Ball Chair in Transplantation.

Dr. Briscoe has held leadership positions, both national and international, including being a member of the Board of Directors of the American Society of Transplantation, Councilor for the International Pediatric Transplant Association, the Executive Committee Chair for the American Transplant Congress, Program Chair in Immunology for the Annual Meeting of the American Society of Nephrology and Chair of the Public Policy Committee for the American Society of Transplantation. In these positions, Dr. Briscoe has been a strong advocate for pediatric transplant recipients, and he is most supportive of discovery-based research and translational studies in the field to impact long-term care. He is also a strong advocate for the education and training of physicians as scientists in biomedical research.

Dr. Briscoe serves on NIH study sections and is a regular reviewer on special grant review committees to provide transplant expertise. He has also served on the editorial board of several transplant journals and is currently the senior editor of Transplantation Direct.

Publications

  1. Detection of Subclinical Rejection in Pediatric Kidney Transplantation: Current and Future Practices. Pediatr Transplant. 2024 Sep; 28(6):e14836. View Abstract
  2. Assessing Vulnerability to COVID-19 in High-Risk Populations: The Role of SARS-CoV-2 Spike-Targeted Serology. Popul Health Manag. 2023 02; 26(1):29-36. View Abstract
  3. A Combination therapy using an mTOR inhibitor and Honokiol effectively induces autophagy through the modulation of AXL and Rubicon in renal cancer cells and restricts renal tumor growth following organ transplantation. Carcinogenesis. 2022 05 19; 43(4):360-370. View Abstract
  4. Inhibition of mevalonate metabolism by statins augments the immunoregulatory phenotype of vascular endothelial cells and inhibits the costimulation of CD4+ T cells. Am J Transplant. 2022 03; 22(3):947-954. View Abstract
  5. T Cell-Specific Adaptor Protein Regulates Mitochondrial Function and CD4+ T Regulatory Cell Activity In Vivo following Transplantation. J Immunol. 2019 10 15; 203(8):2328-2338. View Abstract
  6. Calcineurin inhibitors augment endothelial-to-mesenchymal transition by enhancing proliferation in association with cytokine-mediated activation. Biochem Biophys Res Commun. 2019 11 19; 519(4):667-673. View Abstract
  7. DEPTOR modulates activation responses in CD4+ T cells and enhances immunoregulation following transplantation. Am J Transplant. 2019 01; 19(1):77-88. View Abstract
  8. DEPTOR at the Nexus of Cancer, Metabolism, and Immunity. Physiol Rev. 2018 07 01; 98(3):1765-1803. View Abstract
  9. Study rationale, design, and pretransplantation alloantibody status: A first report of Clinical Trials in Organ Transplantation in Children-04 (CTOTC-04) in pediatric heart transplantation. Am J Transplant. 2018 09; 18(9):2135-2147. View Abstract
  10. Convergent and Divergent Migratory Patterns of Human Neutrophils inside Microfluidic Mazes. Sci Rep. 2018 01 30; 8(1):1887. View Abstract
  11. The intragraft microenvironment as a central determinant of chronic rejection or local immunoregulation/tolerance. Curr Opin Organ Transplant. 2017 Feb; 22(1):55-63. View Abstract
  12. Vascular endothelial growth factor A is associated with the subsequent development of moderate or severe cardiac allograft vasculopathy in pediatric heart transplant recipients. J Heart Lung Transplant. 2017 Apr; 36(4):434-442. View Abstract
  13. Netrin-1 Augments Chemokinesis in CD4+ T Cells In Vitro and Elicits a Proinflammatory Response In Vivo. J Immunol. 2016 08 15; 197(4):1389-98. View Abstract
  14. Cholesterol efflux capacity of high-density lipoprotein correlates with survival and allograft vasculopathy in cardiac transplant recipients. J Heart Lung Transplant. 2016 11; 35(11):1295-1302. View Abstract
  15. Microfluidic mazes to characterize T-cell exploration patterns following activation in vitro. Integr Biol (Camb). 2015 Nov; 7(11):1423-31. View Abstract
  16. Use of [18F]FDG Positron Emission Tomography to Monitor the Development of Cardiac Allograft Rejection. Transplantation. 2015 Sep; 99(9):e132-9. View Abstract
  17. Multicenter Analysis of Immune Biomarkers and Heart Transplant Outcomes: Results of the Clinical Trials in Organ Transplantation-05 Study. Am J Transplant. 2016 Jan; 16(1):121-36. View Abstract
  18. Regulation of mTOR Signaling by Semaphorin 3F-Neuropilin 2 Interactions In Vitro and In Vivo. Sci Rep. 2015 Jul 09; 5:11789. View Abstract
  19. Translational implications of endothelial cell dysfunction in association with chronic allograft rejection. Pediatr Nephrol. 2016 Jan; 31(1):41-51. View Abstract
  20. Chronic allograft rejection: a fresh look. Curr Opin Organ Transplant. 2015 Feb; 20(1):13-20. View Abstract
  21. Microfluidic platform for the quantitative analysis of leukocyte migration signatures. Nat Commun. 2014 Sep 03; 5:4787. View Abstract
  22. Modified mRNA directs the fate of heart progenitor cells and induces vascular regeneration after myocardial infarction. Nat Biotechnol. 2013 Oct; 31(10):898-907. View Abstract
  23. DEPTOR regulates vascular endothelial cell activation and proinflammatory and angiogenic responses. Blood. 2013 Sep 05; 122(10):1833-42. View Abstract
  24. VEGF-C, VEGF-A and related angiogenesis factors as biomarkers of allograft vasculopathy in cardiac transplant recipients. J Heart Lung Transplant. 2013 Jan; 32(1):120-8. View Abstract
  25. Chemokine receptor trio: CXCR3, CXCR4 and CXCR7 crosstalk via CXCL11 and CXCL12. Cytokine Growth Factor Rev. 2013 Feb; 24(1):41-9. View Abstract
  26. Peripherally circulating CD4? FOXP3? CXCR3? T regulatory cells correlate with renal allograft function. Scand J Immunol. 2012 Sep; 76(3):320-8. View Abstract
  27. Targeting the intragraft microenvironment and the development of chronic allograft rejection. Hum Immunol. 2012 Dec; 73(12):1261-8. View Abstract
  28. Constitutive activation of the mTOR signaling pathway within the normal glomerulus. Biochem Biophys Res Commun. 2012 Aug 24; 425(2):244-9. View Abstract
  29. Differential activation of human T cells to allogeneic endothelial cells, epithelial cells and fibroblasts in vitro. Transplant Res. 2012 Apr 24; 1(1):4. View Abstract
  30. Key Features of the Intragraft Microenvironment that Determine Long-Term Survival Following Transplantation. Front Immunol. 2012; 3:54. View Abstract
  31. TRAF6 inhibits proangiogenic signals in endothelial cells and regulates the expression of vascular endothelial growth factor. Biochem Biophys Res Commun. 2012 Mar 02; 419(1):66-71. View Abstract
  32. Subsets of human CD4(+) regulatory T cells express the peripheral homing receptor CXCR3. Eur J Immunol. 2011 Aug; 41(8):2291-302. View Abstract
  33. Cost-related immunosuppressive medication nonadherence among kidney transplant recipients. Clin J Am Soc Nephrol. 2010 Dec; 5(12):2323-8. View Abstract
  34. Effect of vascular endothelial growth factor and its receptor KDR on the transendothelial migration and local trafficking of human T cells in vitro and in vivo. Blood. 2010 Sep 16; 116(11):1980-9. View Abstract
  35. Cutting edge: Vascular endothelial growth factor-mediated signaling in human CD45RO+ CD4+ T cells promotes Akt and ERK activation and costimulates IFN-gamma production. J Immunol. 2010 Jan 15; 184(2):545-9. View Abstract
  36. Calcineurin inhibitors activate the proto-oncogene Ras and promote protumorigenic signals in renal cancer cells. Cancer Res. 2009 Dec 01; 69(23):8902-9. View Abstract
  37. CD40-induced signaling in human endothelial cells results in mTORC2- and Akt-dependent expression of vascular endothelial growth factor in vitro and in vivo. J Immunol. 2008 Dec 01; 181(11):8088-95. View Abstract
  38. mTOR-understanding the clinical effects. Transplant Proc. 2008 Dec; 40(10 Suppl):S9-S12. View Abstract
  39. Calcineurin inhibitors modulate CXCR3 splice variant expression and mediate renal cancer progression. J Am Soc Nephrol. 2008 Dec; 19(12):2437-46. View Abstract
  40. Overexpression of vascular endothelial growth factor and the development of post-transplantation cancer. Cancer Res. 2008 Jul 15; 68(14):5689-98. View Abstract
  41. Assessing the vascular effects of early erythropoietin use in pediatric renal transplant recipients. Nat Clin Pract Nephrol. 2008 Mar; 4(3):136-7. View Abstract
  42. Every allograft needs a silver lining. J Clin Invest. 2007 Dec; 117(12):3645-8. View Abstract
  43. Heme oxygenase-1 modulates the expression of the anti-angiogenic chemokine CXCL-10 in renal tubular epithelial cells. Am J Physiol Renal Physiol. 2007 Oct; 293(4):F1222-30. View Abstract
  44. Organ-specific differences in the function of MCP-1 and CXCR3 during cardiac and skin allograft rejection. Transplantation. 2007 Jun 27; 83(12):1595-601. View Abstract
  45. The effects of mTOR-Akt interactions on anti-apoptotic signaling in vascular endothelial cells. J Biol Chem. 2007 Aug 10; 282(32):23679-86. View Abstract
  46. Ras-induced modulation of CXCL10 and its receptor splice variant CXCR3-B in MDA-MB-435 and MCF-7 cells: relevance for the development of human breast cancer. Cancer Res. 2006 Oct 01; 66(19):9509-18. View Abstract
  47. Pathological angiogenesis is induced by sustained Akt signaling and inhibited by rapamycin. Cancer Cell. 2006 Aug; 10(2):159-70. View Abstract
  48. Vascular endothelial growth factor-induced signaling pathways in endothelial cells that mediate overexpression of the chemokine IFN-gamma-inducible protein of 10 kDa in vitro and in vivo. J Immunol. 2006 Mar 01; 176(5):3098-107. View Abstract
  49. Angiogenesis and endothelial cell repair in renal disease and allograft rejection. J Am Soc Nephrol. 2006 Apr; 17(4):932-42. View Abstract
  50. Vascular endothelial growth factor antagonist modulates leukocyte trafficking and protects mouse livers against ischemia/reperfusion injury. Am J Pathol. 2006 Feb; 168(2):695-705. View Abstract
  51. Function of the vascular endothelial growth factor receptors Flt-1 and Flk-1/KDR in the alloimmune response in vivo. Transplantation. 2005 Sep 27; 80(6):717-22. View Abstract
  52. Vascular endothelial growth factor impairs the functional ability of dendritic cells through Id pathways. Biochem Biophys Res Commun. 2005 Aug 19; 334(1):193-198. View Abstract
  53. CD40: a mediator of pro- and anti-inflammatory signals in renal tubular epithelial cells. J Am Soc Nephrol. 2005 Sep; 16(9):2714-23. View Abstract
  54. The CD154-CD40 T-cell co-stimulation pathway in liver ischemia and reperfusion inflammatory responses. Transplantation. 2005 May 15; 79(9):1078-83. View Abstract
  55. TNP-470, an angiogenesis inhibitor, attenuates the development of allograft vasculopathy. Transplantation. 2004 Oct 27; 78(8):1218-21. View Abstract
  56. The CD40-induced signaling pathway in endothelial cells resulting in the overexpression of vascular endothelial growth factor involves Ras and phosphatidylinositol 3-kinase. J Immunol. 2004 Jun 15; 172(12):7503-9. View Abstract
  57. CD40-induced transcriptional activation of vascular endothelial growth factor involves a 68-bp region of the promoter containing a CpG island. Am J Physiol Renal Physiol. 2004 Sep; 287(3):F512-20. View Abstract
  58. Safety and pharmacokinetics of ascending single doses of sirolimus (Rapamune, rapamycin) in pediatric patients with stable chronic renal failure undergoing dialysis. Pediatr Transplant. 2004 Apr; 8(2):151-60. View Abstract
  59. Proinflammatory functions of vascular endothelial growth factor in alloimmunity. J Clin Invest. 2003 Dec; 112(11):1655-65. View Abstract
  60. Proangiogenic function of CD40 ligand-CD40 interactions. J Immunol. 2003 Aug 01; 171(3):1534-41. View Abstract
  61. Expression patterns of vascular endothelial growth factor in human cardiac allografts: association with rejection. Transplantation. 2003 Jul 15; 76(1):224-30. View Abstract
  62. P-glycoprotein and alloimmune T-cell activation. Clin Appl Immunol Rev. 2003 Jul; 4(1):3-14. View Abstract
  63. Endothelial injury: cause and effect of alloimmune inflammation. Transpl Infect Dis. 2002 Sep; 4(3):152-9. View Abstract
  64. Long-term care of pediatric renal transplant patients: from bench to bedside. Curr Opin Pediatr. 2002 Apr; 14(2):205-10. View Abstract
  65. A rendezvous before rejection: where do T cells meet transplant antigens? Nat Med. 2002 Mar; 8(3):220-2. View Abstract
  66. Hyporesponsiveness in pediatric recipients. Pediatr Transplant. 2002 Feb; 6(1):8-11. View Abstract
  67. Expression of the chemokine receptor CXCR3 and its ligand IP-10 during human cardiac allograft rejection. Circulation. 2001 Nov 20; 104(21):2558-64. View Abstract
  68. Immunologic targets for currently available immunosuppressive agents: what is the optimal approach for children? Semin Nephrol. 2001 Sep; 21(5):508-20. View Abstract
  69. Risk factors for mortality in infants and young children on dialysis. Am J Kidney Dis. 2001 Mar; 37(3):573-9. View Abstract
  70. Specific MDR1 P-glycoprotein blockade inhibits human alloimmune T cell activation in vitro. J Immunol. 2001 Feb 15; 166(4):2451-9. View Abstract
  71. Consensus statement on the live organ donor. JAMA. 2000 Dec 13; 284(22):2919-26. View Abstract
  72. Ligation of CD40 induces the expression of vascular endothelial growth factor by endothelial cells and monocytes and promotes angiogenesis in vivo. Blood. 2000 Dec 01; 96(12):3801-8. View Abstract
  73. The role of the graft endothelium in transplant rejection: evidence that endothelial activation may serve as a clinical marker for the development of chronic rejection. Pediatr Transplant. 2000 Nov; 4(4):252-60. View Abstract
  74. Telecytologic diagnosis of breast fine needle aspiration biopsies. Intraobserver concordance. Acta Cytol. 2000 Mar-Apr; 44(2):175-80. View Abstract
  75. Challenges after pediatric transplantation. Semin Nephrol. 2000 Mar; 20(2):199-208. View Abstract
  76. Endothelial cells modify the costimulatory capacity of transmigrating leukocytes and promote CD28-mediated CD4(+) T cell alloactivation. J Exp Med. 1999 Aug 16; 190(4):555-66. View Abstract
  77. The allogeneic response to cultured human skin equivalent in the hu-PBL-SCID mouse model of skin rejection. Transplantation. 1999 Jun 27; 67(12):1590-9. View Abstract
  78. Angiogenesis in the huPBL-SCID model of human transplant rejection. Transplantation. 1999 Jun 27; 67(12):1626-31. View Abstract
  79. The use of standardized orbital ultrasound in the diagnosis of sinus induced infections of the orbit in children: a preliminary report. Int J Pediatr Otorhinolaryngol. 1999 May 05; 48(2):155-62. View Abstract
  80. Current understanding of chemokine involvement in allograft transplantation. Pediatr Transplant. 1999 Feb; 3(1):10-21. View Abstract
  81. Interactions between T lymphocytes and endothelial cells in allograft rejection. Curr Opin Immunol. 1998 Oct; 10(5):525-31. View Abstract
  82. Pediatric renal transplantation: indications and special considerations. A position paper from the Pediatric Committee of the American Society of Transplant Physicians. Pediatr Transplant. 1998 May; 2(2):117-29. View Abstract
  83. Central role for CD40/CD40 ligand (CD154) interactions in transplant rejection. Pediatr Transplant. 1998 Feb; 2(1):6-15. View Abstract
  84. CD40 and CD40 ligand (CD154) are coexpressed on microvessels in vivo in human cardiac allograft rejection. Transplantation. 1997 Dec 27; 64(12):1765-74. View Abstract
  85. Human endothelial cell costimulation of T cell IFN-gamma production. J Immunol. 1997 Oct 01; 159(7):3247-56. View Abstract
  86. The problem of chronic rejection: influence of leukocyte-endothelial interactions. Kidney Int Suppl. 1997 Mar; 58:S22-7. View Abstract
  87. Differential regulation of leucocyte L-selectin (CD62L) expression in normal lymphoid and inflamed extralymphoid tissues. J Clin Pathol. 1996 Sep; 49(9):721-7. View Abstract
  88. P-selectin expression in myocardium of children undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1995 Oct; 110(4 Pt 1):924-33. View Abstract
  89. Antigen-dependent activation of T helper cell subsets by endothelium. Transplantation. 1995 Jun 15; 59(11):1638-41. View Abstract
  90. Predictive value of inducible endothelial cell adhesion molecule expression for acute rejection of human cardiac allografts. Transplantation. 1995 Jan 27; 59(2):204-11. View Abstract
  91. Water channel vesicles from toad urinary bladder contain a family of proteins present in other tissues. Am J Physiol. 1994 May; 266(5 Pt 1):C1366-75. View Abstract
  92. Role of leukocyte-endothelial cell adhesion molecules in renal inflammation: in vitro and in vivo studies. Kidney Int Suppl. 1993 Jul; 42:S27-34. View Abstract
  93. Alpha 1-VIII collagen is expressed in the rat glomerulus and in resident glomerular cells. Am J Physiol. 1993 Jun; 264(6 Pt 2):F1003-10. View Abstract
  94. Duplex Doppler examination of renal allografts in children: correlation between renal blood flow and clinical findings. Pediatr Radiol. 1993; 23(5):365-8. View Abstract
  95. Expression of vascular cell adhesion molecule-1 in human renal allografts. J Am Soc Nephrol. 1992 Nov; 3(5):1180-5. View Abstract
  96. Effects of tumor necrosis factor, lipopolysaccharide, and IL-4 on the expression of vascular cell adhesion molecule-1 in vivo. Correlation with CD3+ T cell infiltration. J Immunol. 1992 Nov 01; 149(9):2954-60. View Abstract
  97. Outcome of renal transplantation in children less than two years of age. Kidney Int. 1992 Sep; 42(3):657-62. View Abstract
  98. Childhood membranoproliferative glomerulonephritis type I: limited steroid therapy. Kidney Int. 1992 Jun; 41(6):1606-12. View Abstract
  99. Induced expression of endothelial-leukocyte adhesion molecules in human cardiac allografts. Transplantation. 1991 Feb; 51(2):537-9. View Abstract
  100. The mode of recognition of allogeneic tissue in the solitary urochordate Styela plicata. Transplantation. 1988 Jun; 45(6):1123-6. View Abstract
  101. Prognosis in Guillain-Barré syndrome. Arch Dis Child. 1987 Jul; 62(7):733-5. View Abstract
  102. Loss of secretion in mouse-human hybrids need not be due to the loss of a structural gene. J Exp Med. 1982 Nov 01; 156(5):1380-9. View Abstract

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