The research proposal describes a 2-year mentored-research plan designed to provide the principal investigator (PI) with a foundation from which to pursue a career in geriatric research. The PI has completed a residency in Internal Medicine at Duke University followed by dual fellowship training in both Medical Oncology and Geriatrics at Duke University. She is currently an Assistant Professor in the Department of Medicine, Division of Cell Therapy and the Division of Geriatrics. The proposed project seeks to explore biologic markers of functional decline in elderly patients with Acute Myeloid Leukemia (AML), and correlate them with clinical markers via Comprehensive Geriatric Assessment (CGA). Dr. Harvey Jay Cohen, the Walter Kemper Professor of Medicine at Duke University and the Director of the Duke Center for Aging will serve as the primary mentor for the PI's scientific development. He is a recipient of the Duke Research Mentoring Award has an extensive history training thought leaders in the medical sciences, and has worked closely with the PI since her residency training. All laboratory analysis will be conducted under the guidance of Dr. Dav?, an expert in genomic studies, micro RNA, and DNA and RNA sequencing in hematologic malignancies. He will serve as the PI's secondary mentor. In addition, the PI's progress will receive regular scientific and career counsel from an advisory committee of respected investigators in geriatric research. The PI's previous work has demonstrated that differences in the underlying biology i.e. higher probability of Src, TNF, and RAS oncogenic pathway activation in elderly AML patients as compared to their younger counterparts contributes to poor survival. In addition, gene expression data for cytokines associated with frailty was utilized to create a genomic predictor for frailty, and she been able to show that this is a far more sensitive way to predict for survival compared to just the traditional ECOG PS measure. Duke University Medical Center provides the PI with an ideal environment to launch a multidiscipline research career focused on assessment of functional status in elderly patients with AML. Our investigative team at Duke is unique since we have expertise in all three fields of study: geriatrics, oncology, and genomics that have a longstanding history of working well with each other. By designing a research and mentoring plan that takes advantage of the strengths of the different research disciplines, the proposed research plan maximizes the PI's efforts to establish herself as a thought leader at the interface of oncology, genomics, and geriatrics.
ECOG Performance Status is an important prognostic factor in elderly patients with Acute Myeloid Leukemia (AML), and mortality from induction therapy ranges from 30- 80%. It is, however, a very subjective measure, and does not accurately predict for functional decline, unlike Comprehensive Geriatric Assessment (CGA). The proposed research herein will better understand the proteomic and genomic predictors of functional decline, correlate them with clinical predictors via CGA, and finally create a combined clinico-genomic model to predict functional decline and mortality from induction therapy in this population.
|Nipp, Ryan D; Rao, Arati V (2015) Performance status in elderly patients with acute myeloid leukemia: exploring gene expression signatures of cytokines and chemokines. J Gerontol A Biol Sci Med Sci 70:714-21|
|Morris, Tod A; DeCastro, Carlos M; Diehl, Louis F et al. (2013) Re-induction therapy decisions based on day 14 bone marrow biopsy in acute myeloid leukemia. Leuk Res 37:28-31|
|Rao, Arati V; Smith, B Douglas (2013) Are results of targeted gene sequencing ready to be used for clinical decision making for patients with acute myelogenous leukemia? Curr Hematol Malig Rep 8:149-55|