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Myeloid cells (granulocytes and monocytes) play critical
roles in immune and inflammatory responses. The differentiation of myeloid
cells from immature bone marrow precursor cells is characterized by tightly
regulated gene transcription. Leukemia is a clinical manifestation of
abnormal myeloid differentiation and many forms of leukemia are caused by
molecular defects in the factors that control myeloid gene transcription.
We cloned the gene that encodes CD18 ( 2 leukocyte integrin) in order to
characterize the DNA sequences and transcription factors that control gene
expression during myeloid differentiation. We showed that combinatorial
interactions between lineage-restricted and more widely expressed factors
regulate the expression of CD18 and other myeloid genes. We are
characterizing the role of the unique ets transcription factor, GABP, in
regulating myeloid gene expression and cell development.
Our studies will better define the mechanisms that regulate gene
transcription during normal myeloid differentiation and provide insights
into the molecular basis of leukemia.
Gyrd-Hansen Mad, Krag TOB, Rosmarin AG, Khurana TS.
Sp1 and the ets-related transcription factor complex GABPa/ß functionally
cooperate to activate the utrophin promoter. J. Neurological Sciences,
197:27-35, 2002.
Bush TS, St. Coeur M, Resendes KK, Rosmarin AG. GA Binding
Protein (GABP) and Sp1 are required, along with Retinoid Receptors to
mediate retinoic acid responsiveness of CD18 (ß2 Leukocyte Integrin):
a novel mechanism of transcriptional regulation in myeloid cells. Blood
in press.
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Associate Professor
M.D., Rutgers University, 1981
The Miriam Hospital, Research, Rm. 215
(401) 793-4648
Rosmarin@brown.edu
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