Patricia Ernst, Ph.D.Assistant Professor of Genetics Contact Information
Phone: 603-650-1134
Postal Address
Dartmouth Medical School
Address for Parcels
Dartmouth Medical School
Education
University of Washington, Seattle, B.S. (1985-1990)
Program Membership Cancer Mechanisms Research Program Department Membership Genetics Graduate Training Program Affiliation Molecular and Cellular Biology Biography Patricia Ernst is an Assistant Professor in the Department of Genetics at Dartmouth Medical School. She received a B.S. in Biochemistry from the University of Washington and Ph.D. from U.C.L.A. in Microbiology and Immunology. She performed postdoctoral studies with Dr. Korsmeyer at Harvard Medical School, where she was a Damon Runyon Fellow and a Special Fellow of the Leukemia and Lymphoma Society. Currently she is the recipient of a Career Development Award from the N.I.D.D.K., the Sydney Kimmel Scholar’s Award, and a Scholar Award from The V Foundation. Selected Recent Publications Hsieh J, Ernst P, Erdjument-Bromage H, Tempst P, Korsmeyer SJ. Proteolytic cleavage of MLL generates a complex of N- and C-terminal fragments that confers protein stability and subnuclear localization. Mol Cell Biol. 23:186-194, 2003Davidson A, Ernst P, Wang Y, Dekens MPS, Kinglsey PD, Palis J, Korsmeyer SJ, Daley G and Zon LI*. Cdx4 mutants fail to specify haematopoietic progenitors during embryogenesis and can be rescued by multiple Hox genes. Nature 425:300-306, 2003 Ernst P, Fisher J, Avery W, Wade S, Foy D, and Korsmeyer SJ. Definitive Hematopoiesis Requires the Mixed Lineage Leukemia Gene. Dev Cell 6(3):437-443, 2004 Ernst P, Mabon M, Davidson AJ, Zon LI, and Korsmeyer SJ. An Mll-dependent Hox Program Drives Hematopoietic Progenitor Expansion. Current Biology, 14(22), 2063-2069, 2004 Wang J, Iwasaki H, Kristov A, Febbo PG, Thorner AR, Ernst P, Anastasiadou E, Kutok JL, Kogan SC, Zinkel SS, Fisher JK, Hess JL, Golub TR, Armstrong SA Akashi K and SJ Korsmeyer*. Conditional MLL-CBP targets GMP and models therapy-related myeloproliferative disease. EMBO J 24(2);361-381, 2005 Wang Y, Yates F, Naveiras O, Ernst P and GQ Daley. Embryonic stem cell-derived hematopoietic stem cells. PNAS 102(52);19081-19086, 2005 Bansal D, Fröhling S, Scholl C, Mcdowell E, Lee BH, Döhner K, Ernst P, Zon LI, Gilliland DG, and BJP Huntly. Cdx4 dysregulates Hox gene expression and generates acute myeloid leukemia alone, and in cooperation with Meis1a, in a murine model. PNAS 109(45):16924-16969, 2006. Jude CD, Climer L, Xu D, Artinger E, Fisher JK, and P Ernst. Unique and independent roles for MLL in adult hematopoietic stem cells and progenitors. Cell Stem Cell 1(3);doi:10.1016/ j.stem.2007.05.019, 2007
Research / Lab Interests The Ernst laboratory focuses on pathways regulating hematopoietic stem cell development, maintenance, and leukemogenesis. The Mixed Lineage Leukemia gene (Mll) is disrupted by chromosomal translocation in a subset of childhood leukemias with a particularly poor prognosis. To understand how Mll fusion oncogenes perturb normal blood cell development and result in leukemia, we have developed a conditional knockout animal since Mll is an essential gene in the mouse. Our studies reveal two distinct roles during blood cell development through the analysis of our conditional knockout mouse model. Using the Irradiation and Flow Cytometry shared resources, we have demonstrated that both hematopoietic stem cells and progenitor cells require Mll to maintain blood cell production in the adult bone marrow. Also a result of the sophisticated cell sorting capabilities of the Flow Cytometry shared resource, we demonstrated that Mll-deficient hematopoietic stem cells prematurely exit from quiescence. Using the Microarray shared resource and bioinformatics collaborations in NCCC, we plan to identify novel pathways and downstream target genes regulated by Mll that participate in maintaining stem cells in a quiescent state. Our group plans to broadly identify the overlap between genes influenced by Mll fusion oncogenes and genes identified as direct Mll target genes in hematopoietic progenitor cells. Such studies will reveal the degree to which oncogenic forms of Mll perturb normal blood developmental pathways and the degree to which new or ectopic pathways are turned on. These studies will be accomplished with the help of the shared Microarray facility and highly purified progenitor cell types obtained in the Flow Cytometry core facility. Grants, Honors, Invited Lectures NIH R01 HL090036 2007-12, "MLL Function in the Maintenance of the Blood Forming System" 2005-07 Sydney Kimmel Scholar’s Award 2005-2007 V Scholar Award 2005-07 Sydney Kimmel Scholar’s Award 2004-09 Mentored Research Scientist Development Award (K01), N.I.D.D.K. 2001-04 Special Fellow of the Leukemia & Lymphoma Society 1997-2000 Fellow of the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation |
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