Stephen J. Brandt, M.D.

Stephen J. Brandt, M.D.

Professor of Medicine, Division of Hematology/Oncology

Professor of Cell and Developmental Biology

Professor of Cancer Biology

540B Preston Research Building
(615) 936-1809

Molecular regulation of normal and leukemic hematopoiesis

Research Description

Our research focuses on the control of blood cell production and how this is subverted in hematologic malignancy. We have been particularly interested in the oncogene TAL1 (or SCL) that encodes a member of the helix-loop-helix family of transcription factors. Abnormal expression of this gene, originally identified through its involvement by a recurrent chromosomal translocation, constitutes the most frequent gain-of-function mutation in T-cell acute lymphoblastic leukemia (T-ALL). Many helix-loop-helix proteins are important in specification of cell fate, and studies from our lab and others indicate that TAL1 regulates fundamental aspects of hematopoietic differentiation.

We have characterized in detail the expression of TAL1 protein in murine and avian embryogenesis and, most recently, in physiological and pathological vasculogenesis. A series of studies on TAL1 function in erythroid cells have shown this transcription factor undergoes both phosphorylation and acetylation, and we have investigated its interaction with a number of transcriptional coregulators. Work is ongoing to investigate the mechanism by which misexpression of this critical regulator of normal hematopoiesis contributes to leukemic transformation and to identify both its interaction partners and downstream targets. Contemporary techniques of molecular biology and protein biochemistry and both in vitro and in vivo models are used in this research.

Clinical Interest

Leukemias; Lymphomas; Multiple Myeloma