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Christopher H. Lowrey, M.D.

Title(s):
Professor of Medicine
Professor of Pharmacology & Toxicology
Chief, Division of Hematology
Vice Chair, Department of Medicine

Department(s):
Medicine
Pharmacology & Toxicology

Education:
Boston University School of Medicine, MD 1985
University of Pennsylvania, MA 1981
Bowdoin College, BA 1979

Programs:
Norris Cotton Cancer Center
Pharmacology and Toxicology Graduate Program
Program in Experimental and Molecular Medicine
Other

Websites:
http://dms.dartmouth.edu/pharmtox/personnel/faculty/lowrey/
http://dms.dartmouth.edu/pemm/faculty/cancer_biology/
http://cancer.dartmouth.edu/blood_marrow/teamprofile/626/Christopher_H_Lowrey_MD
http://www.dhmc.org/webpage.cfm?site_id=2&org_id=2&morg_id=0&sec_id=16596&gsec_id=16596&item_id=626&utility_id=1&layer=0&parent_id=0&fuseaction=profile

Contact Information:

Christopher H. Lowrey, MD
Section of Hematology/Oncology
Dartmouth-Hitchcock Medical Center
Lebanon NH 03756

Office: 623 Rubin
Phone: 603-653-9967
Fax: 603-650-2334
Email: christopher.h.lowrey@dartmouth.edu

Assistant: Connie Goodrich
Asst. Phone: 603-650-2967
Asst. Email: Constance.M.Goodrich@hitchcock.org


Professional Interests:

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.

Courses Taught:

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

Biography:

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.


Selected Publications:

 

Hahn CK, Lowrey CH
Induction of fetal hemoglobin through enhanced translation efficiency of γ-globin mRNA.
Blood 2014 Aug 28;
PMID: 25170120

Schaeffer EK, West RJ, Conine SJ, Lowrey CH
Multiple physical stresses induce γ-globin gene expression and fetal hemoglobin production in erythroid cells.
Blood Cells Mol Dis 2014 Apr; 52(4):214-24
PMID: 24314748

Preis M, Lowrey CH
Laboratory tests for paroxysmal nocturnal hemoglobinuria.
Am J Hematol 2014 Mar; 89(3):339-41
PMID: 24127129

Bates DJ, Danilov AV, Lowrey CH, Eastman A
Vinblastine rapidly induces NOXA and acutely sensitizes primary chronic lymphocytic leukemia cells to ABT-737.
Mol Cancer Ther 2013 Aug; 12(8):1504-14
PMID: 23723123

Hahn CK, Lowrey CH
Eukaryotic initiation factor 2α phosphorylation mediates fetal hemoglobin induction through a post-transcriptional mechanism.
Blood 2013 Jul 25; 122(4):477-85
PMID: 23690448

Macari ER, Schaeffer EK, West RJ, Lowrey CH
Simvastatin and t-butylhydroquinone suppress KLF1 and BCL11A gene expression and additively increase fetal hemoglobin in primary human erythroid cells.
Blood 2013 Jan 31; 121(5):830-9
PMID: 23223429

Bates DJ, Salerni BL, Lowrey CH, Eastman A
Vinblastine sensitizes leukemia cells to cyclin-dependent kinase inhibitors, inducing acute cell cycle phase-independent apoptosis.
Cancer Biol Ther 2011 Aug 15; 12(4):314-25
PMID: 21768777

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
Novel therapeutic candidates, identified by molecular modeling, induce γ-globin gene expression in vivo.
Blood Cells Mol Dis 2011 Aug 15; 47(2):107-16
PMID: 21641240

Macari ER, Lowrey CH
Induction of human fetal hemoglobin via the NRF2 antioxidant response signaling pathway.
Blood 2011 Jun 2; 117(22):5987-97
PMID: 21464371

Salerni BL, Bates DJ, Albershardt TC, Lowrey CH, Eastman A
Vinblastine induces acute, cell cycle phase-independent apoptosis in some leukemias and lymphomas and can induce acute apoptosis in others when Mcl-1 is suppressed.
Mol Cancer Ther 2010 Apr; 9(4):791-802
PMID: 20371726