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The Briscoe Laboratory |
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David M.
Briscoe M.D. Dr. David M. Briscoe graduated from the Royal College of Surgeons in Ireland in 1982. He performed his initial residency training in General Medicine and Pediatrics in Ireland and at the University of Colorado Health Sciences Center in Denver Colorado. He trained in Vascular Biology in Dr. Jordan Pober’s Laboratory at the Brigham and Women’s Hospital and completed his renal fellowship at the Children’s Hospital Boston in 1991. Subsequently, he extended his post-doctoral research training in Vascular Biology under the mentorship of Dr. Ramzi Cotran. In 1993, Dr. Briscoe joined the Faculty at the Children’s Hospital, Boston and established his own research effort with the support and mentorship of Dr. Andrew Lichtman, Brigham and Women’s Hospital. Dr. Briscoe has authored over 60 original publications and review articles. He serves on several advisory committee’s pertaining to transplantation and he is a member and past Councilor of the American Society of Transplantation (AST). In addition, he is a member of the National Physician-Scientist Honors Society, the American Society of Clinical Investigation (ASCI). Dr. Briscoe has received several awards for his research activities including the Basic Science Award of the AST. He served as Executive Program Chair for the American Transplant Congress (ATC) annual meeting 2002-2003, and as the Committee Chair for the American Society of Nephrology 2003 annual meeting (representing immunology and transplantation). He continues to participate in several national organizations and committees in an effort to promote research in transplantation medicine. Dr. Briscoe’s research effort focus's on an understanding of mechanisms by which lymphocytes and monocytes interact with the vascular endothelium in cell-mediated immune inflammatory reactions and allograft rejection. The vascular endothelium represents a unique interface between the recipient blood and the donor graft; ongoing studies test the possibility that the endothelial cell has the capacity to promote or/and inhibit inflammation and the rejection process. Most important contributions made by the Briscoe laboratory include: 1) The original descriptions of the expression of endothelial cell adhesion molecules and chemokines in human allografts, and publications on their mechanistic (and diagnostic) roles in acute and chronic rejection. 2) Studies defining a mechanism whereby the graft endothelium may alter the phenotype of T cells for responsiveness to intragraft cytokines; and a regulatory function of graft endothelial cells in the direct and the indirect pathways of allorecognition. 3) The first description of a functional role for P-glycoprotein in antigen presenting cell function and alloimmune T cell activation; and 4) Studies demonstrating that alloimmune inflammation is associated with angiogenesis, and that CD40L-CD40 signaling and the expression of Vascular Endothelial Growth Factor (VEGF) may represent a mechanistic link between the immune response and angiogenesis. Many of Dr. Briscoe’s trainees have received National Awards for their work including NRSA’s and K awards from the National Institutes of Health, as well as Faculty Career Development Awards from several societies including the AST, the American Heart Association and the National Kidney Foundation. |
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Research Associates |
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Soumitro
Pal, Ph.D. Publications (selected) By way of background, I completed my Ph.D. in a tumor immunobiology program at the University of Calcutta in India. Subsequently, in 1997, I joined the Beth Israel Deaconess Medical Center as a research fellow, and furthered my interest in tumor vascular biology working on the signal transduction pathways that promote angiogenesis. I joined the Children’s Hospital Boston in July 2001. Ongoing studies in my laboratory involve the understanding of (a) intracellular signals in vascular endothelial cells and cancer cells that mediate the induced expression of VEGF, (b) the roles of chemokines, chemokine receptors and angiogenesis factors in the development of post-transplantation cancer, and (c) the role of hemeoxygenase-1 (HO-1) as a cytoprotective molecule in association with tubular injury during renal inflammation. Angiogenesis is well established to be important component of tumor progression as well as chronic inflammation. Our present studies are focused on establishing mechanisms by which the transplantation process facilitates a milieu that may be of importance in tumor development in transplant recipients. It is well known that angiogenesis factors are associated with tumor growth, and we and others have observed that these same factors are increased in expression post transplantation. In addition, chemokines and chemokine receptor-mediated events have been found to promote cancer growth. We have recently observed differences in signals mediated by spliced forms of CXCR3 (called CXCR3A and CXCR3B); and we have reported that commonly used calcineurin inhibitor immunosuppressive medications alter the relative expression of these receptors. We have found that the shift in expression of these receptors is pro-tumorigenic and can facilitate both tumor development and growth. Finally, in other studies on renal tubular injury, we have studied proinflammatory and protective genes that are known to be expressed at select times following injury. We identified that CD40-induced signaling in renal tubular cells (which typically induce proinflammatory genes) can also mediate the expression of protective genes. Thus, we have proposed that there is a balance between the enhanced expression of proinflammatory genes vs. protective genes in these cells. |
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Assistants |
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Katiana
Calzadilla, BS |
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Evelyn
Flynn, BS, MA Evelyn received a M.A. degree in biology from Boston University in 1990. She has worked in the several research areas at Children’s Hospital Boston over the past 15 years and has a special interest in vascular biology and orthopedic research. She specializes in immunohistochemistry and electron microscopy and is a co-author on more than fifty publications. Evelyn is an experienced technologist in the laboratory, and enjoys working with fellows in teaching general laboratory techniques as well as histology/immunohistochemistry. |
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Research Fellows |
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Xiao
Wu , Ph.D.
Xiao received her M.D. and Ph.D. in cancer pathology and cancer vascular biology in the Health Science Center, Peking University, China. Her Ph.D. project focused on the effects of VEGF121 in tumor endothelial cell proliferation and vascularization, and specifically on the use of an anti-sense VEGF cDNA as an anti-angiogenic treatment for human lung giant cell carcinoma. Since joining Children’s Hospital Boston, Xiao worked on human blood-derived endothelial progenitor cells (EPC) in Dr. Joyce Bischoff’s group. She joined Dr. Briscoe’s laboratory to further her studies on human EPC differentiation and their role in immune mediated angiogenesis including signaling pathways involved in their differentiation. |
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Dipak
Datta, Ph.D. Dipak received his Ph.D. from Jadavpur University, Calcutta, India. During his predoctoral training, he studied immunoregulatory chemokines in cancer development. His current studies under the joint mentorship of Dr. Pal and Dr. Briscoe focus on understanding the role of Ras in modulating the expression and function of chemokines and their receptors, and the role of ischemia and reoxygenation on the regulation of chemokines in endothelial cells. |
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Aninda
Basu, Ph.D. Aninda received his Ph.D. from University of Calcutta in India. His pre doctoral studies focused on novel molecular and immunological markers in Breast Cancer. After completing his Ph.D. work he joined Medical College of Ohio where he studied novel phosphorylation sites in the estrogen receptor alpha and the functional role of these phosphorylation sites in signaling pathways. Later, he moved to Tulane University to further these studies. Recently he moved to Boston and joined Dr. Briscoe and Dr. Pal within the Transplantation Research Center at Children’s Hospital Boston. Aninda plans to study the role of VEGF post receptor signaling in endothelial activation responses. In addition, he will study the role of VEGF in the development of post transplantation cancer. |
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Andre Hoerning, M.D. |
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Maria Stack, M.D. Maria graduated in Medicine from the University College Cork, Ireland and trained in general pediatrics within the higher Specialist Training Program in Dublin, Ireland. As a part of this training, Maria was admitted as a member of the Royal College of Physicians in Ireland. She has recently initiated her training in Pediatric Nephrology at Children’s Hospital and joined Dr. Briscoe’s laboratory to initiate research in molecular mechanisms of transplantation rejection. She plans to evaluate endothelial stem cells in patients following organ transplantation and will use novel transgenic mice to study how the graft may manipulate and determine the rejection process. |
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Tatsuichiro Seto, M.D. Tatsu graduated from Yamagata University School of Medicine, Yamagata in Japan in 1995. Prior to joining Dr. Briscoe’s laboratory he trained as a cardiovascular surgeon in Shinshu University Hospital, Matsumoto, Japan. He has significant expertise in the development and use of animal models of rejection. Previously, he studied the role of an apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC) in cardiac allograft rejection. His current studies relate to the analysis of distinct roles for the allograft vasculature in the development of chronic rejection. |
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Gearoid McMahon, M.D. Gearoid received his medical degree from the University College Cork in Ireland. While a medical student he worked in the laboratory and returned to Ireland to complete his initial training in medicine. He has joined the laboratory this year as a research fellow and plans to develop his skills in both in vitro cell molecular analyses, and he plans to use in vivo models for some of his studies. His project involves an understanding of cell protection signaling pathways in endothelial cells and crosstalk among signals with the mTOR kinase. |
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| 2008 | 2006 | |
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| 2003 | 2001 |
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Michelle
Baum, M.D. 1994-1995 Michael
Melter, M.D. 1998-2000 |
Masayuki Sho, M.D., Ph.D. 1999- 2002 Stefan
Kiessling, M.D. 2002-2004 Jesse Flaxenburg, M.D. 2002-2005 |
Atsushi Izawa, M.D., Ph.D. 2002-2005 Olivier Dormond, M.D., Ph.D. 2003-2007 Monika Edelbauer, M.D. 2006-2008 Alan Contreras, M.D. 2003-2008 |
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| Christopher Geehan J.D. 1996-2007 Chris served as the Briscoe Laboratory Manager and as the Manager of the newly formed Pediatric Transplantation Research Laboratories from 1996-2007. During this time, Chris attended Law School and passed the Massachussetts Bar in 2006. He currently works in the Intellectual Property Office of Children’s Hospital Boston as a member of their Legal team. |
Kerrith Koss BS 2001-2003 Kerrith served as a technician in the laboratory from 2001-2003. She left the laboratory to re-enter University as a graduate student in 2004. |
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| Marlies Reinders Mentored Ph.D. Thesis, University of Leiden, Holland |
Esther Meijer 2006-2007 Mentored M.D. Thesis University of Groningen, Holland |
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Gearoid McMahon 1998 Jeanette Reiners 2000 |
William Wong 1999-2004 BS and M.D. Student Christopher Burke 2002 BS Student Kevin Gaughan 2008 BS Student |