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Alan G Rosmarin MD

InstitutionUMass Chan Medical School
AddressUMass Chan Medical School
55 Lake Avenue North
Worcester MA 01655
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    Other Positions
    InstitutionT.H. Chan School of Medicine

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentTranslational Science

    Collapse Biography 
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    Vassar College, Poughkeepsie, NY, United StatesBABiology
    University of Medicine and Dentistry of New Jersey, Newark, NJ, United StatesMDMedicine

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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.

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Epstein MM, Saphirak C, Zhou Y, LeBlanc C, Rosmarin AG, Ash A, Singh S, Fisher K, Birmann BM, Gurwitz JH. Identifying monoclonal gammopathy of undetermined significance in electronic health data. Pharmacoepidemiol Drug Saf. 2020 01; 29(1):69-76. PMID: 31736189.
      Citations: 3     Fields:    Translation:Humans
    2. Hsu A, Gagnier M, Ryer E, Salhab M, Rosmarin AG. Hypercalcemia due to Primary Hepatic Lymphoma. Case Rep Hematol. 2016; 2016:1876901. PMID: 28116183.
    3. Malu K, Garhwal R, Pelletier MG, Gotur D, Halene S, Zwerger M, Yang ZF, Rosmarin AG, Gaines P. Cooperative Activity of GABP with PU.1 or C/EBPe Regulates Lamin B Receptor Gene Expression, Implicating Their Roles in Granulocyte Nuclear Maturation. J Immunol. 2016 08 01; 197(3):910-22. PMID: 27342846.
      Citations: 5     Fields:    Translation:HumansAnimalsCells
    4. Buckle G, Maranda L, Skiles J, Ong'echa JM, Foley J, Epstein M, Vik TA, Schroeder A, Lemberger J, Rosmarin A, Remick SC, Bailey JA, Vulule J, Otieno JA, Moormann AM. Factors influencing survival among Kenyan children diagnosed with endemic Burkitt lymphoma between 2003 and 2011: A historical cohort study. Int J Cancer. 2016 Sep 15; 139(6):1231-40. PMID: 27136063.
      Citations: 25     Fields:    Translation:HumansPHPublic Health
    5. Lamba G, Zaidi SK, Luebbers K, Verschraegen C, Stein GS, Rosmarin A. Epigenetic landscape of acute myelogenous leukemia--moving toward personalized medicine. J Cell Biochem. 2014 Oct; 115(10):1669-72. PMID: 24905899.
      Citations: 4     Fields:    Translation:HumansCells
    6. Yang ZF, Drumea K, Mott S, Wang J, Rosmarin AG. GABP transcription factor (nuclear respiratory factor 2) is required for mitochondrial biogenesis. Mol Cell Biol. 2014 Sep; 34(17):3194-201. PMID: 24958105.
      Citations: 46     Fields:    Translation:AnimalsCells
    7. Yang ZF, Zhang H, Ma L, Peng C, Chen Y, Wang J, Green MR, Li S, Rosmarin AG. GABP transcription factor is required for development of chronic myelogenous leukemia via its control of PRKD2. Proc Natl Acad Sci U S A. 2013 Feb 05; 110(6):2312-7. PMID: 23345428.
      Citations: 16     Fields:    Translation:AnimalsCells
    8. Zhu XJ, Yang ZF, Chen Y, Wang J, Rosmarin AG. PU.1 is essential for CD11c expression in CD8(+)/CD8(-) lymphoid and monocyte-derived dendritic cells during GM-CSF or FLT3L-induced differentiation. PLoS One. 2012; 7(12):e52141. PMID: 23284905.
      Citations: 10     Fields:    Translation:AnimalsCells
    9. Cerny J, Yu H, Ramanathan M, Raffel GD, Walsh WV, Fortier N, Shanahan L, O'Rourke E, Bednarik J, Barton B, Kroll-Desrosiers A, Hao S, Woda B, Hutchinson L, Evens AM, Rosmarin AG, Nath R. Expression of CD25 independently predicts early treatment failure of acute myeloid leukaemia (AML). Br J Haematol. 2013 Jan; 160(2):262-6. PMID: 23116454.
      Citations: 20     Fields:    Translation:HumansCells
    10. Cerny J, Rosmarin AG. Why does my patient have leukocytosis? Hematol Oncol Clin North Am. 2012 Apr; 26(2):303-19, viii. PMID: 22463829.
      Citations: 9     Fields:    Translation:HumansCells
    11. Reagan JL, Rosmarin A, Butera JN, Nadeem A, Schiffman FJ, Sikov WM, Winer E, Mega AE. Phase I trial examining addition of gemcitabine to CHOP in intermediate grade NHL. Cancer Chemother Pharmacol. 2011 Oct; 68(4):1075-80. PMID: 21761371.
      Citations:    Fields:    Translation:HumansCTClinical Trials
    12. Yang ZF, Drumea K, Cormier J, Wang J, Zhu X, Rosmarin AG. GABP transcription factor is required for myeloid differentiation, in part, through its control of Gfi-1 expression. Blood. 2011 Aug 25; 118(8):2243-53. PMID: 21705494.
      Citations: 13     Fields:    Translation:AnimalsCells
    13. Strother RM, Gregory KM, Pastakia SD, Were P, Tenge C, Busakhala N, Jakait B, Schellhase EM, Rosmarin AG, Loehrer PJ. Retrospective analysis of the efficacy of gemcitabine for previously treated AIDS-associated Kaposi's sarcoma in western Kenya. Oncology. 2010; 78(1):5-11. PMID: 20215784.
      Citations: 7     Fields:    Translation:Humans
    14. Peng C, Chen Y, Yang Z, Zhang H, Osterby L, Rosmarin AG, Li S. PTEN is a tumor suppressor in CML stem cells and BCR-ABL-induced leukemias in mice. Blood. 2010 Jan 21; 115(3):626-35. PMID: 19965668.
      Citations: 62     Fields:    Translation:HumansAnimalsCells
    15. Drumea K, Yang ZF, Rosmarin A. Retinoic acid signaling in myelopoiesis. Curr Opin Hematol. 2008 Jan; 15(1):37-41. PMID: 18043244.
      Citations: 11     Fields:    Translation:HumansAnimalsCells
    16. Yang ZF, Mott S, Rosmarin AG. The Ets transcription factor GABP is required for cell-cycle progression. Nat Cell Biol. 2007 Mar; 9(3):339-46. PMID: 17277770.
      Citations: 63     Fields:    Translation:AnimalsCells
    17. Resendes KK, Rosmarin AG. GA-binding protein and p300 are essential components of a retinoic acid-induced enhanceosome in myeloid cells. Mol Cell Biol. 2006 Apr; 26(8):3060-70. PMID: 16581781.
      Citations: 10     Fields:    Translation:HumansCells
    18. Rosmarin AG, Yang Z, Resendes KK. Transcriptional regulation in myelopoiesis: Hematopoietic fate choice, myeloid differentiation, and leukemogenesis. Exp Hematol. 2005 Feb; 33(2):131-43. PMID: 15676205.
      Citations: 55     Fields:    Translation:HumansAnimalsCells
    19. Rosmarin AG, Resendes KK, Yang Z, McMillan JN, Fleming SL. GA-binding protein transcription factor: a review of GABP as an integrator of intracellular signaling and protein-protein interactions. Blood Cells Mol Dis. 2004 Jan-Feb; 32(1):143-54. PMID: 14757430.
      Citations: 83     Fields:    Translation:HumansCells
    20. Resendes KK, Rosmarin AG. Sp1 control of gene expression in myeloid cells. Crit Rev Eukaryot Gene Expr. 2004; 14(3):171-81. PMID: 15248814.
      Citations: 8     Fields:    Translation:HumansAnimalsCells
    21. 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 (beta 2 leukocyte integrin): a novel mechanism of transcriptional regulation in myeloid cells. Blood. 2003 Jan 01; 101(1):311-7. PMID: 12485937.
      Citations: 18     Fields:    Translation:HumansCells
    22. Gyrd-Hansen M, Krag TO, Rosmarin AG, Khurana TS. Sp1 and the ets-related transcription factor complex GABP alpha/beta functionally cooperate to activate the utrophin promoter. J Neurol Sci. 2002 May 15; 197(1-2):27-35. PMID: 11997063.
      Citations: 9     Fields:    Translation:HumansAnimalsCells
    23. Khanna-Gupta A, Zibello T, Simkevich C, Rosmarin AG, Berliner N. Sp1 and C/EBP are necessary to activate the lactoferrin gene promoter during myeloid differentiation. Blood. 2000 Jun 15; 95(12):3734-41. PMID: 10845904.
      Citations: 10     Fields:    Translation:HumansAnimalsCells
    24. Beckwith C, Butera J, Sadaniantz A, King TC, Fingleton J, Rosmarin AG. Diagnosis in oncology. Case 1: primary transmural cardiac lymphoma. J Clin Oncol. 2000 May; 18(9):1996-7. PMID: 10784641.
      Citations: 4     Fields:    Translation:Humans
    25. Luo M, Shang J, Yang Z, Simkevich CP, Jackson CL, King TC, Rosmarin AG. Characterization and localization to chromosome 7 of psihGABPalpha, a human processed pseudogene related to the ets transcription factor, hGABPalpha. Gene. 1999 Jun 24; 234(1):119-26. PMID: 10393246.
      Citations: 1     Fields:    Translation:HumansCells
    26. Khurana TS, Rosmarin AG, Shang J, Krag TO, Das S, Gammeltoft S. Activation of utrophin promoter by heregulin via the ets-related transcription factor complex GA-binding protein alpha/beta. Mol Biol Cell. 1999 Jun; 10(6):2075-86. PMID: 10359616.
      Citations: 27     Fields:    Translation:AnimalsCells
    27. Nuchprayoon I, Shang J, Simkevich CP, Luo M, Rosmarin AG, Friedman AD. An enhancer located between the neutrophil elastase and proteinase 3 promoters is activated by Sp1 and an Ets factor. J Biol Chem. 1999 Jan 08; 274(2):1085-91. PMID: 9873055.
      Citations: 8     Fields:    Translation:AnimalsCells
    28. Rosmarin AG, Luo M, Caprio DG, Shang J, Simkevich CP. Sp1 cooperates with the ets transcription factor, GABP, to activate the CD18 (beta2 leukocyte integrin) promoter. J Biol Chem. 1998 May 22; 273(21):13097-103. PMID: 9582348.
      Citations: 24     Fields:    Translation:AnimalsCells
    29. Nuchprayoon I, Simkevich CP, Luo M, Friedman AD, Rosmarin AG. GABP cooperates with c-Myb and C/EBP to activate the neutrophil elastase promoter. Blood. 1997 Jun 15; 89(12):4546-54. PMID: 9192779.
      Citations: 16     Fields:    Translation:HumansAnimalsCells
    30. Safran H, King TP, Choy H, Hesketh PJ, Wolf B, Altenhein E, Sikov W, Rosmarin A, Akerley W, Radie-Keane K, Cicchetti G, Lopez F, Bland K, Wanebo HJ. Paclitaxel and concurrent radiation for locally advanced pancreatic and gastric cancer: a phase I study. J Clin Oncol. 1997 Mar; 15(3):901-7. PMID: 9060526.
      Citations: 9     Fields:    Translation:HumansCTClinical Trials
    31. Rosmarin AG, Caprio DG, Simkevich CP. Scanning mutagenesis to localize DNA-protein interactions. Biotechniques. 1997 Mar; 22(3):434-6. PMID: 9067015.
      Citations:    Fields:    Translation:AnimalsCells
    32. Safran H, King T, Choy H, Gollerkeri A, Kwakwa H, Lopez F, Cole B, Myers J, Tarpey J, Rosmarin A. p53 mutations do not predict response to paclitaxel/radiation for nonsmall cell lung carcinoma. Cancer. 1996 Sep 15; 78(6):1203-10. PMID: 8826941.
      Citations: 7     Fields:    Translation:HumansCTClinical Trials
    33. Rosmarin AG, Caprio DG, Kirsch DG, Handa H, Simkevich CP. GABP and PU.1 compete for binding, yet cooperate to increase CD18 (beta 2 leukocyte integrin) transcription. J Biol Chem. 1995 Oct 06; 270(40):23627-33. PMID: 7559529.
      Citations: 15     Fields:    Translation:HumansAnimalsCells
    34. Lasky SR, Iwata K, Rosmarin AG, Caprio DG, Maizel AL. Differential regulation of JunD by dihydroxycholecalciferol in human chronic myelogenous leukemia cells. J Biol Chem. 1995 Aug 25; 270(34):19676-9. PMID: 7649976.
      Citations: 4     Fields:    Translation:HumansCells
    35. Rosmarin AG, Caprio D, Levy R, Simkevich C. CD18 (beta 2 leukocyte integrin) promoter requires PU.1 transcription factor for myeloid activity. Proc Natl Acad Sci U S A. 1995 Jan 31; 92(3):801-5. PMID: 7846055.
      Citations: 17     Fields:    Translation:Cells
    36. Rosmarin AG, Levy R, Tenen DG. Cloning and analysis of the CD18 promoter. Blood. 1992 May 15; 79(10):2598-604. PMID: 1350225.
      Citations: 8     Fields:    Translation:HumansCells
    37. Mazur EM, Rosmarin AG, Sohl PA, Newton JL, Narendran A. Analysis of the mechanism of anagrelide-induced thrombocytopenia in humans. Blood. 1992 Apr 15; 79(8):1931-7. PMID: 1562721.
      Citations: 15     Fields:    Translation:HumansCells
    38. Pahl HL, Rosmarin AG, Tenen DG. Characterization of the myeloid-specific CD11b promoter. Blood. 1992 Feb 15; 79(4):865-70. PMID: 1346576.
      Citations: 24     Fields:    Translation:HumansCells
    39. Rosmarin AG, Weil SC, Rosner GL, Griffin JD, Arnaout MA, Tenen DG. Differential expression of CD11b/CD18 (Mo1) and myeloperoxidase genes during myeloid differentiation. Blood. 1989 Jan; 73(1):131-6. PMID: 2562920.
      Citations: 29     Fields:    Translation:HumansCells
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