Christopher H. Lowrey, M.D.
Professor of Medicine
Professor of Pharmacology & Toxicology
Chief, Division of Hematology
Vice Chair, Department of Medicine
Pharmacology & Toxicology
Boston University School of Medicine, MD 1985
University of Pennsylvania, MA 1981
Bowdoin College, BA 1979
Norris Cotton Cancer Center
Pharmacology and Toxicology Graduate Program
Program in Experimental and Molecular Medicine
Christopher H. Lowrey, MD
Section of Hematology/Oncology
Dartmouth-Hitchcock Medical Center
Lebanon NH 03756
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.
Our lab is primarily focused on developing therapies for sickle cell disease and beta-thalassemia by targeting underlying molecular mechanisms. These diseases (termed hemoglobinopathies), along with the alpha 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 early childhood. These diseases result from mutations affecting the human beta-globin gene. It turns out that humans have a perfectly good substitute genes (the two gamma-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 are developing 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.
Rotations and Thesis Projects:
Viewing fetal globin gene activation as a problem in cell stress signaling has led to the implication of several distinct pathways and new strategies for turning on fetal globin genes in adult hemoglobinopathy patients. Recent undergraduate and graduate rotation and thesis projects have focused on determining the roles of key pathway members and evaluating new genetic and pharmacologic strategies for reactivating fetal globin gene expression. Similar projects are available as we move forward. Our students utilize state-of-the-art methods including working with primary human blood stem cells, siRNA, shRNA, retroviral vectors, chromatin immunoprecipitation, HPLC and RT-PCR.
"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.
Enhancing Therapy for Leukemia by Inhibiting BCL2 Proteins
Principal Investigator: Alan Eastman, PhD
Role on Project: Co-investigator
Agency: Norris Cotton Cancer Center
Type: Pilot Project Grant
Period 2009 - 2011
Novel Biomarkers and Potential Therapeutic Targets Using an RNA-Based Platform to Profile the Proteome in B-cell Chronic Lymphocytic LeukemiaŁ
Principal Investigator: Craig Tomlinson, PhD
Role on Project: Co-Principle Investigator
Agency: Dartmouth Center for Clinical and Translational Science
Type: Pilot Project Grant
Period 2009 - 2011
Medical Pharmacology (Cancer Chemotherapy) - DMS 2
Scientific Basis of Medicine (Hematology) - DMS 2
Program in Experimental and Molecular Medicine (long-range chromatin structure, leukemia)
Clinical Experience in Hematolgy and Bone Marrow Transplant - DMS4
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.
Schaeffer EK, West RJ, Conine SJ, Lowrey CH
Preis M, Lowrey CH
Bates DJ, Danilov AV, Lowrey CH, Eastman A
Hahn CK, Lowrey CH
Macari ER, Schaeffer EK, West RJ, Lowrey CH
Bates DJ, Salerni BL, Lowrey CH, Eastman A
Boosalis MS, Castaneda SA, Trudel M, Mabaera R, White GL, Lowrey CH, Emery DW, Mpollo MS, Shen L, Wargin WA, Bohacek R, Faller DV, Perrine SP
Macari ER, Lowrey CH
Salerni BL, Bates DJ, Albershardt TC, Lowrey CH, Eastman A
Hsu M, Richardson CA, Olivier E, Qiu C, Bouhassira EE, Lowrey CH, Fiering S