Dr. Brian Belyea
Awarded: K08 with NIH (NIDDK)
Title: Role of Renin Progenitors in Hematopoiesis
Dates: 7/01/2014 thru 03/31/2019
Amount funded for total project: 748,820
Project Abstract: The triggering events and cell of origin for leukemia development are usually unknown. We have recently discovered a novel mouse model of B cell leukemia, in which the Notch mediator RBP-J is deleted within renin-expressing cells. We found that the cell of origin for this model is a B lymphocyte progenitor which expresses renin and experiences malignant transformation upon RBP-J deletion. In this project, we propose to further study renin expression during normal and neoplastic hematopoiesis. We hypothesize that renin-expressing hematopoietic cells represent a primitive component of the hematopoietic system with differential transformative capacity and that RBP-J is necessary for appropriate regulation of these cells. Using in vivo lineage tracing, time and cell specific conditional deletion approaches, gene-expression profiling, and immunophenotyping, we propose to further investigate this novel progenitor cell, including its expression patterns during hematopoietic ontogeny, its contribution to differentiation of hematopoietic organs, and its influence on leukemia development. First, we will study the temporal appearance and identity of renin-expressing cells within hematopoietic organs during embryonic and post-natal life. Second, we will delete RBP-J in renin-expressing cells at specific developmental stages to determine when RBP-J becomes critical to normal development of these cells. Third, we will directly compare the malignant potential of B cell subsets by deletion RBP-J in distinct population of B cells using cell-specific deletion.
Dr. Rebecca Scharf
Awarded: 2014 Doris Duke Clinical Scientist Development Award
Title: Early Predictors and Biomarkers of Cognition and Growth in Impoverished Children
Dates: 07/01/2014 thru 06/30/2017
Amount Funded for total project: 486,000
Project Abstract: More than 200 million children worldwide fail to reach their cognitive potential, simultaneously increasing social costs and diminishing human capital. We propose to identify the longitudinal developmental trajectories that children follow over time and the predictors/biomarkers of infection and malnutrition that are associated with cognitive impairment. Aim 1 examines how well growth (change in height-for-age z-score: deltaHAZ) and Bayley Scales of Infant Development (BSID) form birth to 2 years predict kindergarten readiness and cognition in 6,950 children in the United States from the Early Childhood Longitudinal Study- Birth cohort. Aim 2 examines how early growth (deltaHAZ) and diarrheal illness predict scores on the BSID at 24 months in 600 children from three study sites in Bangladesh, Brazil, and South Africa. Next we will examine long-term cognitive outcomes in 100 young adults from Brazil on whom early studies of malnutrition and enteric disease have been completed. Aim 3 will examine specific biomarkers of impaired cognitive development in children including lower height for age z-score, smaller head circumference, fecal markers of inflammation (neopterin, alpha-anti-trypsin and myeloperoxidase), frequent fever, urinary metabolome and markers of environmental enteropathy (low lactulose: mannitol ratio).Mixed models and longitudinal regression analyses will be used to examine relationships between predictors and developmental outcomes. This proposal leverages decades of collaboration between the University of Virginia and colleagues at three world class research sites in Latin America, Africa and Asia (Universidade Federal in Fortaleza, Brazil; University of Venda in Limpopo, South Africa; and International Centre for Diarrheal Disease Research in Dhaka, Bangladesh).
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