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.
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.
|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|
|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|
|Wagner, Julia A; Rosario, Maximillian; Romee, Rizwan et al. (2017) CD56bright NK cells exhibit potent antitumor responses following IL-15 priming. J Clin Invest 127:4042-4058|
|Johanns, Tanner M; Dunn, Gavin P (2017) Applied Cancer Immunogenomics: Leveraging Neoantigen Discovery in Glioblastoma. Cancer J 23:125-130|
|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|
|Fok, Wilson Chun; Niero, Evandro Luis de Oliveira; Dege, Carissa et al. (2017) p53 Mediates Failure of Human Definitive Hematopoiesis in Dyskeratosis Congenita. Stem Cell Reports 9:409-418|
|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|
|Johanns, Tanner M; Bowman-Kirigin, Jay A; Liu, Connor et al. (2017) Targeting Neoantigens in Glioblastoma: An Overview of Cancer Immunogenomics and Translational Implications. Neurosurgery 64:165-176|
|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|
|Dege, Carissa; Sturgeon, Christopher M (2017) Directed Differentiation of Primitive and Definitive Hematopoietic Progenitors from Human Pluripotent Stem Cells. J Vis Exp :|
Showing the most recent 10 out of 187 publications