Areas of Study

I. Circadian oscillation of hematopoietic stem cells (HSCs) and progenitor egress to peripheral blood is regulated by the Sympathetic nervous system (SNS). Signals from sympathetic nerves control circadian rhythms by targeting mesenchymal stem cells (MSCs) and vascular endothelial cells to express chemokines/cytokines and adhesion molecules, respectively. We seek to decipher the mechanisms of circadian oscillation in the HSC niche and their impact on hematopoiesis and its contribution to pathologies such as aging and myeloproliferative disorders.

 

 

II. Our previous work established that signals from SNS control hematopoietic aging and highlight niche-derived factors as critical regulators of HSC longevity, the rejuvenation of which can directly benefit aged stem cells (Maryanovich et al., Nature Medicine 2018). Future efforts are oriented toward identifying targets downstream of the SNS that control niche and HSC aging.

 

 

III. Myeloid malignancies elicit alterations to the HSC niche that promote oncogenic expansion and eradication of healthy stem cells. The SNS was shown to be protective against myeloproliferation, as sympathetic denervation or deletion of β- adrenoreceptors accelerated the development of myeloproliferative disease (Hanoun et al., Cell Stem Cell 2014). Our work has shown that SNS signals control the homeostasis of niche-derived ROS and that leukemic progression favors high oxidative stress, suggesting that SNS signals may mitigate ROS levels in the BM microenvironment to protect HSC niches during leukemogenesis.

 

 

IV. Metabolic activity of niche constituents and perturb their ability to support hematopoiesis. We seek to decipher the role of mitochondrial dynamics and metabolism in dictating MSC function both in vitro and in vivo. We are particularly interested in many aspects of mitochondrial function and their role in dictating MSC phenotypes and HSC support.