Email: Office Phone: 318-675-5763
Laboratory Phone: 318-675-4160
Office Fax: 318-675-5764
Postdoctoral Study, University of Alabama School of Medicine in Birmingham
Ph .D., Biochemistry, 1969, Vanderbilt University
B.S., Chemistry, 1965, Illinois Wesleyan University
Major Research Interests:
Ontogeny of B Lymphocytes during Fetal and Neonatal Development
B cell generation from pluripotent hematopoietic stem cells (PHSC) is part of the overall process of hematopoiesis. Throughout life the hematopoietic system is maintained by a population of self-renewing pluripotent hematopoietic stem cells that can generate all of the hematopoietic cells: including erythrocytes, megakaryocytes, granulocytes, monocytes, and lymphocytes. The cell fate decisions in hematopoiesis are critically dependent on the timely initiation of transcription from stage- and lineage-dependent genes as well as the silencing of lineage inappropriate genes. Gene expression guiding cell fate decisions is regulated by transcription factors (TF's) that confer cell specificity by regulating lineage-specific genes, including growth factor receptors. Therefore, expression of specific TF's and the concerted action of extracellular signals provided by the microenvironment of the bone marrow combine to govern lineage specific differentiation. Furthermore, the level of expression of TF's is also important in the regulation of cell type-specific differentiation. Over- or under-expression of a particular factor can greatly influence the fate of a particular lineage of hematopoietic cells. The experimental focus of this lab utilizes an in vitro growth system that allows the differentiation of primitive hematopoietic progenitors, isolated from BM, into committed B-lymphocyte precursors. This in vitro system encompasses several stages of development where the progenitor cells are subject to cell-fate decisions that determine there ultimate lineage. This in vitro culture system along with our ability to study expression of multiple genes at the single cell level will allow us to determine the temporal pattern of expression of transcriptional regulators that have been shown to be critical for B cell development. Determining the relative levels of gene expression as differentiating cells transverse checkpoints that affect cell fate decisions will provide important information for understanding how coordinated gene expression affects transitions from one stage of development to another. Specifically, we will determine: 1) the relative expression of transcription factors in define populations of bone marrow hematopoietic 2) correlate the relative expression of transcriptions factors with phenotype in single cells; and 3) determine the change in the relative expression of transcription factors in cultures of single cells that are forced to choose alternative cell fates by changing the growth factors present in the medium.
Chronic ingestion of alcohol can affect many aspects of hematopoiesis and the function of hematopoietic lineage cells. Another major focus of this lab is to determine the mechanisms by which alcohol affects the regulation of hematopoietic development during fetal, neonatal, and adult life.
Moscatello, K. M., Biber, K. L., Dempsy, D., Chervenak, R., and Wolcott, R. M., Characterization of a B cell progenitor present in neonatal bone marrow and spleen but not in adult bone marrow and spleen. J. Immunol. 161:5391-5398, 1998.
Biber, K. L., Moscatello, K. M., Dempsy, D., Chervenak, R., and Wolcott, R. M., Effects of in utero alcohol exposure on B cell development in the murine fetal liver. Alcohol Clin. Exp. Res. 22:1706-1712, 1998.
Moscatello, K. M., Biber, K. L., Jennings, S. R., Chervenak, R. C., and Wolcott, R. M., Phenotypic analysis of lymphoid development in neonatal mice exposed in utero to ethanol. Cellular Immunol. 191:124-130, 1999.
Wang, H., Zhou, H., Moscatello, K.M., Dixon, C., Brunson, L.E., Chervenak, R, Chervenak, D., Zhao, X., and Wolcott, R.M., In Utero Exposure to Alcohol Alters Cell Fate Decisions by Hematopoietic Progenitors in the Bone Marrow of offspring Mice During Neonatal Development. Cellular Immunol. 239:75-85, 2006.