George Stamatoyannopoulos, M.D., Dr.Sci.


header

Professor of Medicine and Genome Sciences
Adjunct Professor of Pathology
Director, Markey Molecular Medicine Center

University of Washington
K-240A Health Sciences Building
Medical Genetics, Box 357720
Seattle, WA 98195-7720

Phone: (206) 543-3526
FAX: (206) 221-5112
E-mail: gstam@u.washington.edu



Research Program:


Dr. Stamatoyannopoulos' lab works in five areas:

  1. The control of human globin genes during development and differentiation. Our group has defined two molecular mechanisms of globin gene switching, gene silencing and gene competition among globin genes for interaction with a powerful upstream regulatory element, the locus control region (LCR). Current studies focus on the analysis of sequences involved in globin gene silencing; the delineation of the mechanism of LCR/gene interactions; and the identification of sequences involved in the developmental clock of globin gene switching. We have obtained evidence that the trans control of globin gene switching is combinatorial and involves interactions between specific cis elements and ubiquitous as well as erythroid specific transcriptional factors. Experimental systems used include transgenic mice, manipulations of human embryonic stem cells, genetic knockouts, RNAi, and CHIP technologies.

  2. The development of treatments for sickle cell disease through pharmacologic induction of fetal hemoglobin. The laboratory has a long-standing interest in this field. The currently used hydroxyurea treatment for induction of fetal hemoglobin in sickle cell disease is based on investigations carried out by our lab. Current emphasis is on the delineation of the mechanism of fetal hemoglobin induction by inhibitors of histone deacetylase and the discovery of new inducers of fetal hemoglobin.

  3. The development of somatic gene therapy for ß chain hemoglobinopathies. Sickle cell disease and ß thalassemia can be cured if normal globin genes could be efficiently transferred into the patient's hemopoietic stem cells. The lab focuses on the identification of chromatin insulators which could protect the therapeutic genes from the effects of the site of integration and prevent the activation of endogenous oncogenes by the enhancers contained in the viral vectors. Our group also conducts clinical trials in the Gene Therapy Center established in Papanikolaou hospital in Thessaloniki Greece. A clinical trial directed by our affiliate faculty, Dr. Yannaki, and supported by NIH currently focuses on the development of safe and effective stem cell mobilization in patients with thalassemia major. A trial on gene therapy of severe thalassemia is planned to start in 2010.

  4. The identification and delineation of regulatory elements of the human genome. The lab participates in the ENCODE project, the goal of which is the identification of all the regulatory elements contained in the human genome. New high throughput methods for identification of DNAse I hypersensitive sites have been developed by the lab of the PI of the project Dr. John Stamatoyannopoulos (Department of Genome Science). Regulatory elements so identified are further characterized by postdoctoral fellows.

  5. The investigation of molecular genetics of Bronze Age populations inhabiting the Aegean basin. This study focuses on the delineation of the genetics of Minoans, the population which inhabited the island of Crete 3,500 to 5,500 thousand years ago and the Myceneans who inhabited the mainland and islands of Greece around 3,500 years ago. Mitochondrial sequencing is used and we are also planning to experiment with whole genome sequencing of ancient DNA using the newest high throughput sequencing approaches.

Investigator: Dr. Stamatoyannopoulos is a Professor of Medicine (Medical Genetics) and Genome Sciences and Adjunct Professor of Pathology.



Representative Publications: