Although advances in hematology have led the way in many fields of basic and translational biomedical research, hematologic diseases remain major threats to public health. For example, the prognosis for many hematologic malignancies continues to be poor. Current treatments are inadequate to support a normal lifestyle for most patients with for sickle cell disease. In the U.S., at least 500,000 venous thromboembolic events, 1.1 million heart attacks and 150,000 stroke deaths occur each year. At the same time, the opportunities for hematology research have never been more promising, and converting these opportunities into medical advances will depend upon training the next generation of basic and translational hematology researchers. The Molecular Hematology training program proposes to fill this need for 5 predoctoral and 8 postdoctoral trainees per year. Predoctoral Ph.D. and M.D./PhD students follow the curriculum of the Washington University graduate school. After passing their qualifying examination, they enter the laboratory of participating faculty Mentors (currently 23) for 3-4 years of laboratory research to complete their dissertation. Postdoctoral Ph.D. trainees from around the world apply to participating laboratories;postdoctoral M.D. and M.D./Ph.D. trainees usually have completed the clinical training component of a Hematology-Oncology fellowship program at Washington University or elsewhere. The duration of postdoctoral training depends on prior experience. Those with Ph.D. or M.D./PhD degrees typically conduct research for 2-3 years before transitioning to an independent research position, whereas those with an M.D. degree may benefit from 3-4 years of postdoctoral training. Trainees receive intensive mentoring and career counseling, and participate in coursework, journal clubs, and seminars. The major facilities of the program consist of 55,000 square feet of fully-equipped laboratory space that house the Divisions of Hematology and Oncology, as well as extensive institutional resources for genome sequencing, crystallography, computational biology, animal studies, and patient-oriented clinical research. The research topics available to trainees reflect the multidisciplinary expertise of the participating Mentors and include: pathogenesis of hemorrhagic and thrombotic disorders;regulation of blood coagulation and fibrinolysis;gene therapy of hemophilia and lysosomal storage diseases;phosphoinositide metabolism and cell signaling pathways;mechanisms of hematopoiesis;telomerase and ribosomal protein defects in bone marrow failure syndromes;molecular basis for protein trafficking in mammalian cells;role of platelets and angiogenesis in metastasis;biology of human immunodeficiency and leukemia viruses;epithelial morphogenesis;pathogenesis of leukemia, MDS, myeloproliferative neoplasms, and congenital neutropenia;cell cycle control;programmed cell death in development and malignancy. Completion of this program will prepare talented trainees for careers in basic and translational hematology research, to make discoveries that will transform the diagnosis and treatment of hematologic diseases.

Public Health Relevance

Blood diseases like leukemia, sickle cell disease, anemia, venous thrombosis, and stroke affect millions of people in the U.S. The goal of this grant is to train a new generation of scientists who will make discoveries that enable us to diagnose, treat, and perhaps cure these diseases.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Institutional National Research Service Award (T32)
Project #
5T32HL007088-38
Application #
8454227
Study Section
NHLBI Institutional Training Mechanism Review Committee (NITM)
Program Officer
Chang, Henry
Project Start
1975-07-01
Project End
2016-02-29
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
38
Fiscal Year
2013
Total Cost
$526,917
Indirect Cost
$45,091
Name
Washington University
Department
None
Type
Other Domestic Higher Education
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Engle, E K; Fisher, D A C; Miller, C A et al. (2015) Clonal evolution revealed by whole genome sequencing in a case of primary myelofibrosis transformed to secondary acute myeloid leukemia. Leukemia 29:869-76
Jacoby, M A; De Jesus Pizarro, R E; Shao, J et al. (2014) The DNA double-strand break response is abnormal in myeloblasts from patients with therapy-related acute myeloid leukemia. Leukemia 28:1242-51
Russler-Germain, David A; Spencer, David H; Young, Margaret A et al. (2014) The R882H DNMT3A mutation associated with AML dominantly inhibits wild-type DNMT3A by blocking its ability to form active tetramers. Cancer Cell 25:442-54
Grieselhuber, N R; Klco, J M; Verdoni, A M et al. (2013) Notch signaling in acute promyelocytic leukemia. Leukemia 27:1548-57
Collier, Timothy S; Diraviyam, Karthikeyan; Monsey, John et al. (2013) Carboxyl group footprinting mass spectrometry and molecular dynamics identify key interactions in the HER2-HER3 receptor tyrosine kinase interface. J Biol Chem 288:25254-64
Boyer, Alaina P; Collier, Timothy S; Vidavsky, Ilan et al. (2013) Quantitative proteomics with siRNA screening identifies novel mechanisms of trastuzumab resistance in HER2 amplified breast cancers. Mol Cell Proteomics 12:180-93
Zhang, Kaihua; Kim, Seokho; Cremasco, Viviana et al. (2011) CD8+ T cells regulate bone tumor burden independent of osteoclast resorption. Cancer Res 71:4799-808
Wartman, Lukas D; Larson, David E; Xiang, Zhifu et al. (2011) Sequencing a mouse acute promyelocytic leukemia genome reveals genetic events relevant for disease progression. J Clin Invest 121:1445-55
Uy, Geoffrey L; Lane, Andrew A; Welch, John S et al. (2010) A protease-resistant PML-RAR{alpha} has increased leukemogenic potential in a murine model of acute promyelocytic leukemia. Blood 116:3604-10
Qian, Yi; West, Christopher M; Kornfeld, Stuart (2010) UDP-GlcNAc:Glycoprotein N-acetylglucosamine-1-phosphotransferase mediates the initial step in the formation of the methylphosphomannosyl residues on the high mannose oligosaccharides of Dictyostelium discoideum glycoproteins. Biochem Biophys Res Commun 393:678-81

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