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./Ph.D. students follow the curriculum of the Washington University graduate school. After passing their qualifying examination, they enter the laboratory of participating faculty Mentors (currently 27) 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./Ph.D. 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 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, myelodysplastic syndrome, 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 #
5T32HL007088-42
Application #
9254581
Study Section
Special Emphasis Panel (NITM (OA))
Program Officer
Chang, Henry
Project Start
1975-07-01
Project End
2021-03-31
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
42
Fiscal Year
2017
Total Cost
$624,202
Indirect Cost
$50,774
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Celik, Hamza; Koh, Won Kyun; Kramer, Ashley C et al. (2018) JARID2 Functions as a Tumor Suppressor in Myeloid Neoplasms by Repressing Self-Renewal in Hematopoietic Progenitor Cells. Cancer Cell 34:741-756.e8
Trissal, Maria C; Wong, Terrence N; Yao, Juo-Chin et al. (2018) MIR142 Loss-of-Function Mutations Derepress ASH1L to Increase HOXA Gene Expression and Promote Leukemogenesis. Cancer Res 78:3510-3521
Ostrander, Elizabeth L; Koh, Won Kyun; Mallaney, Cates et al. (2018) The GNASR201C mutation associated with clonal hematopoiesis supports transplantable hematopoietic stem cell activity. Exp Hematol 57:14-20
Creamer, J Philip; Dege, Carissa; Ren, Qihao et al. (2017) Human definitive hematopoietic specification from pluripotent stem cells is regulated by mesodermal expression of CDX4. Blood 129:2988-2992
Fisher, D A C; Malkova, O; Engle, E K et al. (2017) Mass cytometry analysis reveals hyperactive NF Kappa B signaling in myelofibrosis and secondary acute myeloid leukemia. Leukemia 31:1962-1974
Shirai, Cara Lunn; White, Brian S; Tripathi, Manorama et al. (2017) Mutant U2AF1-expressing cells are sensitive to pharmacological modulation of the spliceosome. Nat Commun 8:14060
Wagner, Julia A; Berrien-Elliott, Melissa M; Rosario, Maximillian et al. (2017) Cytokine-Induced Memory-Like Differentiation Enhances Unlicensed Natural Killer Cell Antileukemia and Fc?RIIIa-Triggered Responses. Biol Blood Marrow Transplant 23:398-404
Cole, Christopher B; Russler-Germain, David A; Ketkar, Shamika et al. (2017) Haploinsufficiency for DNA methyltransferase 3A predisposes hematopoietic cells to myeloid malignancies. J Clin Invest 127:3657-3674
Johanns, Tanner M; Dunn, Gavin P (2017) Applied Cancer Immunogenomics: Leveraging Neoantigen Discovery in Glioblastoma. Cancer J 23:125-130
Kramer, A C; Kothari, A; Wilson, W C et al. (2017) Dnmt3a regulates T-cell development and suppresses T-ALL transformation. Leukemia 31:2479-2490

Showing the most recent 10 out of 190 publications