Leukocyte Development

BIOGRAPHY

ACADEMIC POSITION:
Professor of Pathology and Medicine, University of Utah

EDUCATION:
• BS University of Montana, Missoula
• PhD University of Utah

RESEARCH INTERESTS:
My laboratory works with various models of stem cell biology. Two areas of research are of particular interest to us. In the first area, the laboratory utilizes NIH-approved human embryonic stem (hES) cell lines to investigate the development of blood during embryogenesis. These experiments allow us to study a human developmental question in a model system that is reproducible, since the cell lines can be maintained in culture indefinitely and can be induced to differentiate into blood lineages by manipulation of culture conditions. In contrast, analysis of blood development from adult-derived blood stem cells involves isolation of these cells from patient samples, which vary widely due to genetic differences, diagnosis, and the degree of prior treatment for disease. We are able to induce hES cells to differentiate into many of the normal blood lineage cells, opening up the possibility for us to study the molecular determinants underlying the process of blood development. We plan to apply gene transfer technology in this model system in order to develop in vitro models of human diseases such as hemoglobinopathies and leukemia.

Our second area of research interest pertaining to stem cell biology focuses on adult stem cell populations obtained from mouse bone marrow tissue. We have devoted many years to elucidating the developmental pathway leading from stem cell to mature lymphocyte in the mouse model. We have identified several intermediate stages in this process, and have adopted in vitro techniques that allow us to follow lymphoid development in a controlled culture environment. These studies will help us understand how lymphocyte cells are generated from adult stem cells, and will be useful in designing protocols to enhance lymphoid engraftment following bone marrow transplantation.

Using fluorescent antibodies as probes to label specific cell populations, we are able to identify and isolate the stem cells found in normal mouse and human bone marrow using fluorescence-activated cell sorting (FACS). This technology allows us to isolate defined cell populations that can then be studied in culture or in transplantation models. We can evaluate the functions of stem cell populations isolated after various treatments, such as chemotherapy, infections, inflammation, and during the aging process. We can also study how the cells respond to culture conditions and growth factors in order to better model the early stages of blood development in culture. This work will lead to a better understanding of the molecular control of blood development and eventual applications in clinical medicine.