Obesity perturbs metabolic homeostasis and has adverse effects on health. Obese patients have compromised immune function, increased risk for a hematological malignancy, and increased risk for non-relapse mortality following either autologous or allogeneic bone marrow transplantation. Abnormalities in hematopoiesis occur in obese individuals and may underlie their compromised immune and hematopoietic functions. We propose to investigate the molecular and cellular mechanisms that underlie deregulated hematopoiesis in obese patients. The overall hypothesis to be investigated is that obesity perturbs metabolic homeostasis in hematopoietic stem cells (HSCs), resulting in compromised HSC function and hematopoiesis. Supporting this hypothesis is our recent finding that a nutrient sensor, whose activity is inversely regulated by nutritional input, regulates mitochondrial metabolic homeostasis to promote stress resistance in HSCs and promotes their self-renewal and hematopoiesis under stress. We plan to greatly expand this initial finding to systemically investigate how obesity affects HSC function and hematopoiesis.
Obesity has adverse effects on human health and profound social impact. This project details a study of hematopoiesis in obese mice that will lead to the elucidation of the molecular and cellular mechanisms regulating this process. This study will have profound implications in opening up a new direction for hematological research with significant pathophysiological relevance.
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| Ohkubo, Rika; Chen, Danica (2017) Aging: rewiring the circadian clock. Nat Struct Mol Biol 24:687-688 |
| Budinger, G R Scott; Kohanski, Ronald A; Gan, Weiniu et al. (2017) The Intersection of Aging Biology and the Pathobiology of Lung Diseases: A Joint NHLBI/NIA Workshop. J Gerontol A Biol Sci Med Sci 72:1492-1500 |
| Luo, Hanzhi; Chiang, Hou-Hsien; Louw, Makensie et al. (2017) Nutrient Sensing and the Oxidative Stress Response. Trends Endocrinol Metab 28:449-460 |
| Mohrin, Mary; Chen, Danica (2016) The mitochondrial metabolic checkpoint and aging of hematopoietic stem cells. Curr Opin Hematol 23:318-24 |
| Shin, Jiyung; Chen, Danica (2016) Molecular, Cellular, and Physiological Characterization of Sirtuin 7 (SIRT7). Methods Mol Biol 1436:271-7 |
