About the McKinney-Freeman Lab

Hematopoietic stem cells (HSCs) are often exploited for therapeutic use. Dysfunction of this cell population lies at the heart of hematological disease. Our laboratory explores the fundamental biology of HSC ontogeny, molecular regulation, and transplantation. This work will illuminate underlying mechanisms of disease. We hope to reveal potential opportunities to improve transplantation-based therapies.

Science Team

Our research summary

Hematopoietic stem cells (HSCs) are routinely used to treat leukemia and hematologic disease through HSC transplantation therapies. Many patients who would benefit from this form of therapy, however, lack access to a suitable donor. Our laboratory explores the fundamental biology of HSCs, particularly the genetic and cellular regulation of their in vivo repopulating activity. By better understanding the factors controlling the ability of HSCs to home to, engraft, and repopulate the hematopoietic compartment after transplantation, we hope to develop better and more effective HSC transplantation therapies.

The projects in our laboratory explore HSC ontogeny, the molecular regulation of HSC transplantation, and the effect of chronic hematologic stress and disease on these stem cells. Our work incorporates several approaches and techniques, including flow cytometry, fate mapping, functional studies, single-cell RNA sequencing, bioinformatics, imaging and pathology. 

HSC ontogeny

In this line of investigation, our laboratory aims to better understand the precise way in which HSCs emerge during embryogenesis and how the hematopoietic hierarchy is established in the bone marrow during fetal and early life. Recently, we have isolated HSC populations of interest across the entire course of mammalian development – from mid-gestation through four weeks of age – to take a deeper look at the heterogenicity of the bone marrow niche and the HSC pool across this relatively unexplored window of HSC ontogeny. Using novel fate-mapping technologies, we are able to apply a bioinformatics-based approach to analyze cell populations during early development and across lifespan. 

   The projects in our laboratory explore HSC ontogeny, the molecular regulation of HSC transplantation, and the effect of chronic hematologic stress and disease on these stem cells. Our work incorporates several approaches and techniques, including flow cytometry, fate mapping, functional studies, single-cell RNA sequencing, bioinformatics, imaging and pathology.

Molecular regulation of HSC transplantation

Another area of research in our laboratory focuses on the molecular regulation of HSC following transplantation. Using an unbiased screening approach, we identified a large number of putative genetic regulators previously unidentified in the context of HSC biology. From this screen, we have prioritized multiple candidates for follow-up studies using mouse models and molecular approaches to illuminate precisely how they control HSC function. We are now translating our discoveries to human HSC and leveraging them to enhance HSC transplantation, especially in contexts where HSC engraftment is compromised (e.g. hematopoietic disease). Increasing our understanding of engraftment regulation, we envision robust collaboration with the Department of Chemical Biology and Therapeutics to explore small molecule-based interventions for improved transplant efficiency. 

Molecular regulation of HSC transplantation

HSC and Hematologic Disease

Our laboratory also studies how chronic hematologic stress or chronic hematologic disease corrupt HSC function. We are specifically focusing on sickle cell anemia (SCA), using both mouse models of the disease as well as clinical samples to see how the fitness of the HSCs is compromised in this disease setting. Towards this work, we have developed key partnerships with scientists and clinicians here at St. Jude and in local adult hospitals. Looking ahead, our laboratory seeks to identify the molecular pathways that are perturbed in SCA HSCs and develop strategies to rejuvenate these dysfunctional HSCs, which will benefit cell-based therapies for these patients that depend on their HSCs.

Selected Publications

Journal SMF
Journal 2 SMF

About Shannon McKinney-Freeman

Dr. Shannon McKinney-Freeman received her PhD from Baylor College of Medicine in 2003 in the laboratory of Dr. Margaret Goodell. As a postdoc with Dr. George Daley at Boston Children’s, she characterized the phenotype and function of pluripotent stem cell-derived hematopoietic progenitors, as well as acquired and analyzed the global gene expression profiles of hematopoietic progenitors throughout mammalian ontogeny. McKinney-Freeman joined the Department of Hematology at St. Jude in 2010, and since then has committed her research lab to understanding the basic biology and ontogeny of the hematopoietic system. She is passionate about creating an inclusive and exciting lab environment, characterized by collegiality and scientific excellence.

Shannon McKinney-Freeman, PhD

The team

Enthusiastic and committed team of scientists, leveraging robust expertise in hematopoietic stem cell biology to drive discovery


Life in the Lab

Contact us

Shannon McKinney-Freeman, PhD

Hematology
MS 341
St. Jude Children Research Hospital

262 Danny Thomas Place
Memphis, TN, 38105-3678 USA
901-595-2733 shannon.mckinney-freeman@stjude.org
262 Danny Thomas Place
Memphis, TN, 38105-3678 USA
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