Kay L. Medina, Ph.D., studies the development of B-lineage lymphocytes from blood stem cells. B lymphocytes are a special category of white blood cell that produces antibodies to fight infection. Defects in B cell development or function can cause increased susceptibility to infection, leukemia or autoimmune disease.
The long-term goal of Dr. Medina's research is to understand how B cells are made from stem cells to better understand how their production or function is altered in disease.
Dr. Medina's laboratory uses multiparameter flow cytometry and a variety of established and newly generated mutant mouse models, together with various complex in vitro culture model systems designed to mimic the bone marrow microenvironment where B cells develop, to identify and characterize the biological processes that selectively drive the generation of B lymphocytes from bone marrow hematopoietic stem cells (HSCs).
The laboratory also examines blood from human subjects to identify novel immune correlates that might be informative in aiding the diagnosis of immunodeficiency diseases or enhancing vaccine responses.
- What are the critical regulatory proteins expressed in blood stem cells required for the generation of B cell progenitors? Currently, Dr. Medina's research is focused on identifying the regulatory connection between the stem cell fate determinant Hoxa9 and the receptor tyrosine kinase Flt3. Dr. Medina discovered that blood stem cells from mice deficient for Hoxa9 show impaired Flt3 expression. Flt3 signaling is limiting for activating the B cell developmental program in HSCs.
- How does Flt3 signaling regulate the development of B lymphocytes from HSCs? Flt3 is a signaling molecule and an oncogene, and its expression is tightly controlled. Flt3+ cells in bone marrow are rare, making their isolation challenging. Dr. Medina has generated non-transformed multipotent Flt3+ cell lines to learn how Flt3 signaling regulates B cell development.
Significance to patient care
The overall goals of Dr. Medina's research are to:
- Better understand mechanisms of B cell development to boost production of B cells in the aged or after therapy-related ablation and/or stem cell transplantation
- Identify immune parameters that can be manipulated to maximize B cell vaccine responses
- Pinpoint genetic perturbations leading to immunodeficiencies