Ramnik Xavier Laboratory

Ramnik Xavier, MD
Assistant Professor in Medicine
Harvard Medical School

Address:

Massachusetts General Hospital
Simches Research Building
Boston, MA 02114
Phone: (617) 726-8687 Fax: (617) 724-6832

Ramnik Xavier's Molecular Biology Webpage

Lab Members:

  • Alan Huett, Ph.D.
  • Zhifang Cao, Ph.D.
  • Aimee Landry
  • Yair Benita, Ph.D.
  • Aylwin Ng, MSC Ph.D.
  • Petric Kuballa, Ph.D.

Current Projects:

Functional analysis of PDZ domain - PDZ ligand interactions

Scaffold proteins with PDZ domains are known to coordinate multiple signaling molecules and to couple membrane events to the underlying cytoskeleton. Using genetic and molecular approaches we are investigating the role of PDZ domain containing scaffold proteins in T cell receptor signaling and intestinal epithelial biology. We are particularly interested in understanding how scaffold proteins modulate positive and negative signaling outputs following T cell receptor activation. Given the central importance of PDZ complexes in establishing and maintaining polarity and their link to epithelial cancers of the gastrointestinal tract we are interested in identifying PDZ domain proteins and PDZ ligands that function as oncogenes and tumor suppressors. We have generated knockout ES cells and mice of a number of novel PDZ domain proteins: 1) To define the biochemical functions of these proteins, 2) To track signaling in vivo using GFP/RFP tagged proteins, 3) To elucidate the roles of these proteins in immunity and cancer and 4) Use integrative genomics approaches to gain insights into the role of PDZ ligands in immunity and epithelial cancers.

The genetic analysis of signal transduction pathways that determine host cell responses to microbes and cancer

We have developed a high throughput system for identifying genes that are important in determining host cell responses to pathogens and tumor cells. This method depends on a GFP or luciferase reporter cell line and pooled cDNA library. Arrayed cDNA libraries are transfected into reporter cell lines to identify molecules that activate a signal transduction pathway. After analysis of pooled cDNA by transfection we go back the original single clone directly because pooling is done in two dimensions. We are interested in identifying molecules that activate serum response element, NF-kB and HIF-1a using this method.

To integrate novel Inflammatory Bowel Disease genes into signaling and regulatory pathways using knockout/knockin mice, biochemistry, proteomics and computational approaches.

Past Lab Members

  • Ashish Chawla MD, Assistant Professor, University of Pennsylvania
  • Kazuhiro Ishiguro MD, PhD, Assistant Professor, Nagoya University Medical School, Japan
  • Heather Wachtel, Medical Student, Yale Medical School
  • Julio Bernabe Ortiz PhD, Professor of Molecular Biology, Catholic University, Arequipa, Peru
  • Michael Choi MD, Instructor in Medicine, Massachusetts General Hospital
  • Niko Andre MD, Medizinische Universitatsklinik,  Bochum, Germany.

Recent Publications:

  • Colucci R, Fleming JV, Xavier R, Wang TC. L-Histidine decarboxylase decreases its own transcription through downregulation of ERK activity. Am Journal of Physiol 2001;281:G1081-G1091.

  • Xavier R, Podolsky DK. How to get along - friendly microbes in a hostile world. Science 2000, Sept 1;1483-1484.

  • Mankin H, Rosenthal D, Xavier R. Gaucher Disease: New Approaches to an Ancient Disease. J. Bone & Joint Disease. 2001;83-A:748-762.

  • Merscher S, Funke B, Epstein JA, Heyer J, Puech A, Lu MM, Xavier RJ, Demay MB, Russell RG, Factor S, Tokooya K, St. Jore B, Lopez M, Pandita RK, Lia M, Carrion D, Xu H, Schorle H, Kobler JB, Scambler P, Wynshaw-Boris A, Skoultchi A, Morrow BE, Kucherlapati R. TBX1 is responsible for cardiovascular defects in Velo-Cardio-Facial/DiGeorge Syndrome. Cell 2001;104:619-629.

  • Chung RT, He W, Saquib A, Contreras AM, Xavier RJ, Chawla A, Wang TC, Schmidt EV. Hepatitis C virus replication is directly inhibited by IFN-alpha in a full-length binary expression system. Proc Natl Acad Sci 2001;98(17):9847-9852.

  • Schiffmann R, Mankin H, Dambrosia JM, Xavier RJ, Kreps C, Hill SC, Barton NW, Rosenthal DI. Decreased bone density in splenectomized Gaucher patients receiving enzyme replacement therapy. Blood Cells Mol Dis 2002;2:288-96.

  • Khokhlatchev A, Rabizadeh S, Savier R, Nedwidek M, Chen T, Zhang XF, Seed B, Avruch J. Identification of a novel Ras-regulated proapoptotic pathway. Curr Biol 2002;12(7):253-265.

  • Mizoguchi E, Mizoguchi A, Takedatsu H, Cario E, de Jong YP, Ooi CJ, Xavier RJ, Terhorst C, Podolsky DK, Bhan AK. Role of tumor necrosis factor receptor 2 (TNFR2) in colonic epithelial hyperplasia and chronic intestinal inflammation in mice. 2002;122(1):134-144.