The goal of this Mentored Patient-Oriented Research Career Development Award (K23) is to assist Dr. Magdalena Czader in the development into an independent competitive investigator with comprehensive multidisciplinary expertise applicable to clinical and translational research. Two integral parts of this application are: 1) a patient-oriented research proposal and 2) didactic training program. In her research Dr. Magdalena Czader will investigate the clinical applications of proteomic and computational methods in pediatric acute lymphoblastic leukemia. The emphasis will be placed on comparative protein profiling of leukemic cells and normal bone marrow precursors, the integration of the proteomic results with other biological and clinical information, and multiparameter analysis using novel visualization tools to derive clinically relevant information. The following hypotheses will be tested: 1) protein profiles of acute lymphoblastic leukemia are different from those seen in their normal bone marrow counterparts, 2) leukemic cells of acute lymphoblastic leukemia display a distinctive protein profile predictive of response to chemotherapy and long term outcome. Acute lymphoblastic leukemia is the most common pediatric malignancy with approximately 2,500 new cases diagnosed annually. It is the most common cause of death from malignancy in children younger than 14 years of age. The prediction of prognosis, which influences the choice of treatment, is not accurate. Up to 20 percent of children with projected good outcome will experience the recurrence of the disease. Thus, it is critical to develop novel methods to identify patients with different prognosis and to guide therapy. It is expected that better prognostic indicator(s) will be found using high throughput mass spectrometry-based proteomic methods and computational analysis of multiparameters databases. In addition, the comparison of protein profiles of leukemic cells and normal bone marrow precursors has a potential to identify disease biomarkers and novel drug targets. All proposed analyses require high quality patient tissue. The leukemia bank with well-annotated samples will be maintained and updated with new specimens. The formal didactic training will include comprehensive mentorship by Marc Overhage, M.D., Munro Peacock, M.D. and Michael Borowitz, M.D., Ph.D., formal coursework at Clinical Investigator Training Enhancement program and graduate courses at Indiana University. This additional training is essential for Dr. Czader to achieve expertise in computational methods, database design and proteomics. Completing the outlined training program and research proposal will allow Dr. Czader to transform into independent competitive clinical investigator.
