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Christopher H. Lowrey, M.D.

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Research Description: Role of epigenetics and cell stress signaling in normal and disease-related blood cell production; development of novel pharmacologic therapies for sickle cell disease, thalassemia and leukemia.

Dr. Lowrey received his BA in Biochemistry from Bowdoin College in 1979 and his MA, also in Biochemistry, from the University of Pennsylvania in 1982. He received his MD from Boston University School of Medicine in 1985 and subsequently performed his residency in internal medicine at Tufts New England Medical Center in Boston and at the National Institutes of Health Clinical Center in Bethesda, MD. He then served as a Medical Staff Fellow and Senior Staff Fellow in the Clinical Hematology Branch of the National Heart, Lung, and Blood Institute of N.I.H. where he completed his fellowship in Hematology in 1992. In 1993 he joined the faculty of Dartmouth Medical School where he holds a joint appointment in the Departments of Medicine and Pharmacology.

Our lab is primarily focused on developing therapies for sickle cell disease and -thalassemia by targeting underlying molecular mechanisms. These diseases (termed hemoglobinopathies), along with the  thalassemias, affect more people world-wide than any other class of genetic disease. While patients with access to modern medical care live into middle age, they must often deal with severe side effects. People with these diseases who do not have access to modern medical care often do not live beyond childhood. These diseases result from mutations affecting the human -globin gene. It turns out that humans have a perfectly good substitute genes (the two -globin genes) that are normally only expressed during fetal development. Proof of principle studies have shown that if these genes can be turned on in adult patients then their conditions can be dramatically improved. Unfortunately, all currently available drugs that activate the fetal globin genes lack the effectiveness, safety profile and ease of use that would make them applicable to most people with these diseases. In our lab we are studying the mechanisms by which the fetal globin genes are silenced following birth and how known inducers of the genes work to reactivate their expression. Our work includes studying the role of DNA methylation and histone modification (epigenetics) and the role of cell signaling in these processes. By identifying key pathways and regulatory molecules we hope to develop novel targeted pharmacologic agents for fetal hemoglobin induction that will be safe and effective so that they can be used to treat patients throughout the world.

Courses Taught:

Medical Pharmacology (Cancer Chemotherapy) - DMS 2
Scientific Basis of Medicine (Hematology) - DMS 2
Program in Experimental and Molecular Medicine
Clinical Experience in Hematolgy and Bone Marrow Transplant - DMS4

Grant Information:

"Regulation of Beta-Globin Locus Chromatin Structure"
Principal Investigator: Christopher H. Lowrey
Agency: National Heart, Lung and Blood Institute
Type: RO1 (HL52243)
Period: 1994 - 2008
Description: The major goals of this project are to determine the regulatory elements which are responsible for forming the erythroid-specific chromatin structures of the locus and to then apply these elements to the design of new gene therapy vectors.

"Mechanisms Underlying the Pharmacologic Induction of Fetal Hemoglobin"
Principal Investigator: Christopher H. Lowrey
Agency: National Heart, Lung and Blood Institute
Type: R01 (HL73442)
Period:2003 - 2011
Description: Although more than 70 drugs have been shown to induce fetal hemoglobin in various systems, none of these agents are optimal for treating most people with hemoglobinopathies. In addition, the underlying mechanisms by which these drugs induce fetal hemoglobin has not been determined. The major focus of the current iteration of this project is to determine the role of cell stress signaling in fetal hemoglobin induction and to identify novel targets for drug development.