As an experimental hematologist, I have a long-standing interest in the processes controlling cell fate decisions in the hematopoietic stem cell (HSC) compartment. My focus is on finding out how cell-intrinsic and environmental signals intersect to manage normal blood production and how disrupting this connection may bring malignancy.
I first joined Cincinnati Children’s Hospital in 2013 with almost 15 years of experience in my field. My laboratory is in the department of the Stem Cell Biology Program of the Division of Experimental Hematology and Cancer Biology at Cincinnati Children’s Hospital Medical Center.
Over the years, grants and awards from the National Institute of Health (NHLBI: National Heart, Lung, and Blood Institute), Department of Defense (Congressionally Directed Medical Research Programs) and private foundations (Conquer Cancer Now) have funded my research.
My research areas delve into hematopoietic stem cells, hematopoiesis and leukemia. In my lab, my colleagues and I are attempting to uncover how long-lasting metabolic dysregulations such as obesity or diabetes can change the health of the hematopoietic stem cell compartment. We are particularly looking to better understand the adaptive machinery shielding the hematopoietic stem cell compartment from this abnormal environment.
Our team is attempting to determine how these chronic stress and adaptive processes could lead to long-term blood pathologies progression. Our ultimate goal is to leverage these findings to develop novel therapies and reduce the impact of an irregular metabolic environment on the hematopoietic system.
Some of the recent discoveries that we made in my lab highlight the changes in the hematopoietic stem cell compartment in obesity. Obesity is a type of pathology outlined by an extra buildup of adipose tissue and the development of a multitude of hormonal, immunological and metabolic dysregulations. As such, obesity applies chronic and complex pressure on the hematopoietic system.
Our research indicates that obesity changes the cellular architecture of the hematopoietic stem cell compartment and alters its functions, particularly in response to acute hematopoietic stresses. Our findings illustrate that obesity has an advanced impact on the hematopoietic stem cells and show that some of the properties that these cells acquired in obesity can persist over time even after weight loss or exposure to a healthy metabolic environment.
Mechanistically, this research also identified the transcription factor Gfi1 as a key regulator of the hematopoietic stem cell fate in obesity. We showed that Gfi1 expression is up-regulated by the chronic oxidative stress associated with obesity and modulate the fate of the hematopoietic stem cells by regulating their quiescence status. Lastly, our work reveals a potential cost for this adaptation to obesity as we found that Gfi1 up-regulation contributes to the abnormal stress response of the hematopoietic stem cell compartment in this context.
Our research findings have identified vital cellular and molecular mechanisms by which chronic organismal stresses such as obesity impacts the compartment of hematopoietic stem cells and may lead to significant alterations of the compartment’s stability.
PhD: University Renee Descartes, Paris, France, 2004.
Postdoctoral Fellow: University of Chicago/HHMI, Chicago, IL, 2008; University of California, San Francisco, San Francisco, CA, 2013.
Experimental Hematology and Cancer Biology
Lasting Hematopoietic Memory Induced By Gestational Diabetes Contributes to Atherosclerosis Development in Adult Offspring. Blood. 2022; 140:2224-2224.
Hematopoietic Flt3+ Multipotent Progenitors Are Organized in Discrete Functionally and Hierarchically Distinct Populations. Blood. 2022; 140:1981-1982.
Role of the hematopoietic stem cells in immunological memory. Current stem cell reports. 2022; 8:35-43.
FOXO activity adaptation safeguards the hematopoietic stem cell compartment in hyperglycemia. Blood Advances. 2020; 4:5512-5526.
Phenotypic Analysis of the Mouse Hematopoietic Hierarchy Using Spectral Cytometry: From Stem Cell Subsets to Early Progenitor Compartments. Cytometry. Part A : the journal of the International Society for Analytical Cytology. 2020; 97:1057-1065.
The signaling axis atypical protein kinase C λ/ι-Satb2 mediates leukemic transformation of B-cell progenitors. Nature Communications. 2019; 10.
Disruption of the Akt-FoxO Axis As a Safeguard Mechanism for the Hematopoietic Stem Cell Compartment during Chronic Metabolic Stress. Blood. 2019; 134:1201-1201.
Tuning of the Hematopoietic Stem Cell Compartment in its Inflammatory Environment. Current stem cell reports. 2018; 4:189-200.