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ALAN ROSMARIN 07Education:

  • A.B.,Vassar College, 1977
  • M.D., UMDNJ – Rutgers Medical School, 1981
  • M.A. (Hon.), Brown University, 1998

Post-Graduate Training:

  • Resident in Internal Medicine, Beth Israel Hospital/Harvard Medical School, 1981-1984
  • Clinical Fellow in Hematology/Oncology, Beth Israel Hospital, Boston, 1984-1985
  • Research Fellow, Harvard Medical School, Boston, 1985-1987

Honors and Awards:

  • Phi Beta Kappa, Junior Year, 1976
  • Mary Pemberton Nourse Fellowship in Medicine, 1977
  • Alpha Omega Alpha, Junior Year, 1980
  • National Institutes of Health, National Research Service Award, 1984
  • National Institutes of Health, Physician Scientist Award, 1985
  • Beth Israel Hospital, Basic Research Service Award, 1986
  • Harvard Medical School, Milton Fund Award, 1987
  • American Federation for Clinical Research – Henry Christian Award, 1992
  • Brown University, Master of Arts, ad eundem, 1998

Board Certification:

  • American Board of Internal Medicine, 1984
  • American Board of Internal Medicine (Hematology), 1986
  • American Board of Internal Medicine (Oncology), 1987

Myeloid cells (granulocytes and monocytes) are critical for innate immunity and the inflammatory response. Differentiation of myeloid cells from hematopoietic stem cells is tightly regulated, and abnormalities in myeloid differentiation result in leukemia and myelodysplastic syndromes. Gene expression is tightly controlled during normal myeloid differentiation, and abnormalities of transcription factors underlie many forms of leukemia.1 Interests of the laboratory include the regulation of gene transcription in myeloid cells by the ets-related transcription factor, GA-Binding Protein (GABP), and the role of GABP in control of the cell cycle.

beta cells ROSMARINGABP is the only obligate multimeric member of the etsfamily of transcription factors. This tetrameric transcription factor includes two distinct proteins: GABPa binds to DNA through its ets domain, and it recruits the unrelated protein, GABPb, which contains a transcription activation domain. GABPaalso includes a Pointed domain, through which it binds the transcription co-activator, p300.2

cell group ROSMARINGABP regulates the transcription of several important myeloid genes, including CD18 (b2 leukocyte integrin),a4 integrin, neutrophil elastase, and lysozyme. The promoter of the leukocyte integrin, CD18, is bound and activated by GABP in myeloid cells, and GABP is required for transcriptional activation of CD18 in response to retinoic acid.3,4 We identified an enhanceosome, which includes GABP, p300, and retinoic acid receptors, that forms on the CD18 promoter in the presence of retinoic acid; this is the first known retinoic acid-responsive enhanceosome.5 Because abnormalities of retinoic acid receptors cause acute promyelocytic leukemia, these observations suggest that GABP participates in the aberrant differentiation associated with certain forms of leukemia.

Absence of murine Gabpacauses early embryonic lethality, so we generated mice in which we can conditionally disrupt the encoding gene, Gabpa. Disruption of Gabpa dramatically reduces myeloid cells in the peripheral blood and bone marrow. Gabpanull cells contribute poorly to the myeloid compartment, and in vitro and in vivo studies suggest that GABP is required for both proliferation and differentiation of myeloid cells.

cell activity ROSMARINWe generated mouse embryo fibroblasts (MEFs) from floxed Gabpa mice. In vitro disruption of Gabpa causes profound cell cycle arrest as the cells fail to enter S phase. Disruption of Gabpa reduces transcription of the genes that encode DNA Polymerase aand Thymidylate synthase, which are required for DNA synthesis, and Skp2, an E3 ubiquitin ligase that controls protein levels of the Cyclin dependent kinase inhibitors, p21 and p27. Serum stimulates transcription of Gabpa in growth-arrested cells, and expression of Gabpa is sufficient to induce cell cycle entry, even in the absence of serum stimulation. Unexpectedly, GABP regulates the cell cycle without altering expression of D-type cyclins, Cdks, Retinoblastoma (Rb) protein, and E2Fs. These findings indicate that GABP regulates a novel pathway to cell cycle entry that is independent of the canonical Cyclin D/Cdk/Rb/E2F pathway.6


1Rosmarin AG, Yang Z, Resendes KK. Transcriptional Regulation In Myelopoiesis: Hematopoietic Fate Choice, Myeloid Differentiation, And Leukemogenesis, Experimental Hematology, 33: 131-143, 2005.

2Rosmarin AG, Resendes KK, Yang Z, McMillan J, Fleming SL. GA Binding Protein (GABP) Transcription Factor: A Review - GABP as an Integrator of Intracellular Signaling and Protein-Protein Interactions. Blood Cells, Molecules, and Diseases 32: 143-154, 2004.

3 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 (β2 Leukocyte Integrin): a novel mechanism of transcriptional regulation in myeloid cells.Blood, 101:311-317, 2003.

4 Resendes KK, Rosmarin AG. Sp1 Control of Gene Expression in Myeloid Cells. Critical Reviews in Eukaryotic Gene Expression. 14:171-181, 2004.

5 Resendes KK, Rosmarin AG. GABP and p300 are essential components of a retinoic acid induced enhanceosome in myeloid cells. Molecular and Cellular Biology, 26:3060-3070, 2006.

6 Yang Z-Y, Mott S, Rosmarin AG. The ets transcription factor GABP is required for cell cycle progression. Nature Cell Biology, 9:339-346, 2007.

One or more keywords matched the following items that are connected to Rosmarin, Alan
Item TypeName
Academic Article Scanning mutagenesis to localize DNA-protein interactions.
Academic Article GABP cooperates with c-Myb and C/EBP to activate the neutrophil elastase promoter.
Academic Article An enhancer located between the neutrophil elastase and proteinase 3 promoters is activated by Sp1 and an Ets factor.
Academic Article Sp1 cooperates with the ets transcription factor, GABP, to activate the CD18 (beta2 leukocyte integrin) promoter.
Academic Article GA-binding protein (GABP) and Sp1 are required, along with retinoid receptors, to mediate retinoic acid responsiveness of CD18 (beta 2 leukocyte integrin): a novel mechanism of transcriptional regulation in myeloid cells.
Academic Article Activation of utrophin promoter by heregulin via the ets-related transcription factor complex GA-binding protein alpha/beta.
Academic Article Characterization and localization to chromosome 7 of psihGABPalpha, a human processed pseudogene related to the ets transcription factor, hGABPalpha.
Academic Article Sp1 and C/EBP are necessary to activate the lactoferrin gene promoter during myeloid differentiation.
Academic Article The Ets transcription factor GABP is required for cell-cycle progression.
Academic Article Retinoic acid signaling in myelopoiesis.
Academic Article Sp1 and the ets-related transcription factor complex GABP alpha/beta functionally cooperate to activate the utrophin promoter.
Academic Article GA-binding protein transcription factor: a review of GABP as an integrator of intracellular signaling and protein-protein interactions.
Academic Article Differential regulation of JunD by dihydroxycholecalciferol in human chronic myelogenous leukemia cells.
Academic Article CD18 (beta 2 leukocyte integrin) promoter requires PU.1 transcription factor for myeloid activity.
Academic Article Sp1 control of gene expression in myeloid cells.
Academic Article GA-binding protein and p300 are essential components of a retinoic acid-induced enhanceosome in myeloid cells.
Academic Article GABP transcription factor is required for myeloid differentiation, in part, through its control of Gfi-1 expression.
Academic Article GABP transcription factor is required for development of chronic myelogenous leukemia via its control of PRKD2.
Academic Article GABP and PU.1 compete for binding, yet cooperate to increase CD18 (beta 2 leukocyte integrin) transcription.
Concept GA-Binding Protein Transcription Factor
Concept Sp3 Transcription Factor
Concept Transcription Factor AP-1
Concept Transcription Factors
Concept Sp1 Transcription Factor
Academic Article GABP transcription factor (nuclear respiratory factor 2) is required for mitochondrial biogenesis.
Academic Article Cooperative Activity of GABP with PU.1 or C/EBPe Regulates Lamin B Receptor Gene Expression, Implicating Their Roles in Granulocyte Nuclear Maturation.
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