Scott W. Hiebert, Ph.D.

Professor

scott.hiebert@vanderbilt.edu

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Faculty Appointments
Professor of Biochemistry Hortense B. Ingram Chair in Cancer ResearchAssociate Professor of Medicine
Education
Ph.D., Mol. Biol., Northwestern University, Evanston/Chicago, IllinoisB.S., Chemistry, Bethel College, North Newton, Kansas
Office Address
512 PRB
TN 0146
Research Description
The work in my laboratory focuses on determining the normal function of the AML1/RUNX1and ETO family of transcription factors in the regulation of stem cells and gene expression, and how disruption of these genes by chromosomal translocations causes myeloid leukemia. We defined AML1 as a transcription factor that binds the "enhancer core" motif, which regulates the expression of a large number of tissue specific genes. We found that AML1 both activates and represses transcription, and that the translocation fusion proteins inhibit expression of AML1-dependent target genes. We have determined that the t(8;21) fusion protein, AML1/ETO, interacts with the mSin3 and nuclear hormone co-repressors that recruit histone deacetylases to repress transcription. Thus, we have identified a common mechanism for transcriptional repression for these three translocations. Given that these fusion proteins recruit epigenetic modifying enzymes, we are targeting these factors to determine if we can cure this leukemia. We use CRISPR-mediated genetics to modify AML1-ETO for rapid degradation to define its direct target genes. We use cutting-edge genomics methods such as PROseq coupled with small molecule drugs to inhibit chromatin-modifying enzymes to define the mechanism of tumorigenesis and how to attack this cancer.

Research Keywords
Genomic analysis, PROseq, Mass Spectrometry, MUDPIT, ATACseq, RNAseq, ChIPseq, ChIPexo, Molecular Mechanisms of Acute, Leukemia, cell cycle control, and the action of tumor suppressors, Mechanism of action of anti-cancer drugs that target transcription and the epigenome
Publications
Farmer TE, Williams CS, Washington MK, Hiebert SW. Inactivation of the p19(ARF) tumor suppressor affects intestinal epithelial cell proliferation and integrity. J. Cell. Biochem. 2008 Aug 8/15/2008; 104(6): 2228-40. PMID: 18442038, PMCID: PMC3164503, DOI: 10.1002/jcb.21779, ISSN: 1097-4644.

Hanson CA, Wood LD, Hiebert SW. Cellular stress triggers TEL nuclear export via two genetically separable pathways. J. Cell. Biochem. 2008 May 5/15/2008; 104(2): 488-98. PMID: 18022807, DOI: 10.1002/jcb.21637, ISSN: 1097-4644.

Bhaskara S, Chyla BJ, Amann JM, Knutson SK, Cortez D, Sun ZW, Hiebert SW. Deletion of histone deacetylase 3 reveals critical roles in S phase progression and DNA damage control. Mol. Cell. 2008 Apr 4/11/2008; 30(1): 61-72. PMID: 18406327, PMCID: PMC2373760, PII: S1097-2765(08)00207-4, DOI: 10.1016/j.molcel.2008.02.030, ISSN: 1097-4164.

Knutson SK, Chyla BJ, Amann JM, Bhaskara S, Huppert SS, Hiebert SW. Liver-specific deletion of histone deacetylase 3 disrupts metabolic transcriptional networks. EMBO J [print-electronic]. 2008 Apr 4/9/2008; 27(7): 1017-28. PMID: 18354499, PMCID: PMC2323257, PII: emboj200851, DOI: 10.1038/emboj.2008.51, ISSN: 1460-2075.

Moore AC, Amann JM, Williams CS, Tahinci E, Farmer TE, Martinez JA, Yang G, Luce KS, Lee E, Hiebert SW. Myeloid translocation gene family members associate with T-cell factors (TCFs) and influence TCF-dependent transcription. Mol. Cell. Biol [print-electronic]. 2008 Feb; 28(3): 977-87. PMID: 18039847, PMCID: PMC2223385, PII: MCB.01242-07, DOI: 10.1128/MCB.01242-07, ISSN: 1098-5549.

Yang G, Thompson MA, Brandt SJ, Hiebert SW. Histone deacetylase inhibitors induce the degradation of the t(8;21) fusion oncoprotein. Oncogene [print-electronic]. 2007 Jan 1/4/2007; 26(1): 91-101. PMID: 16799637, PII: 1209760, DOI: 10.1038/sj.onc.1209760, ISSN: 0950-9232.

Reed-Inderbitzin E, Moreno-Miralles I, Vanden-Eynden SK, Xie J, Lutterbach B, Durst-Goodwin KL, Luce KS, Irvin BJ, Cleary ML, Brandt SJ, Hiebert SW. RUNX1 associates with histone deacetylases and SUV39H1 to repress transcription. Oncogene [print-electronic]. 2006 Sep 9/21/2006; 25(42): 5777-86. PMID: 16652147, PII: 1209591, DOI: 10.1038/sj.onc.1209591, ISSN: 0950-9232.

Martinez JA, Williams CS, Amann JM, Ellis TC, Moreno-Miralles I, Washington MK, Gregoli P, Hiebert SW. Deletion of Mtgr1 sensitizes the colonic epithelium to dextran sodium sulfate-induced colitis. Gastroenterology. 2006 Aug; 131(2): 579-88. PMID: 16890610, PII: S0016-5085(06)01238-8, DOI: 10.1053/j.gastro.2006.06.009, ISSN: 0016-5085.

Moreno-Miralles I, Pan L, Keates-Baleeiro J, Durst-Goodwin K, Yang C, Kim HG, Thompson MA, Klug CA, Cleveland JL, Hiebert SW. The inv(16) cooperates with ARF haploinsufficiency to induce acute myeloid leukemia. J. Biol. Chem [print-electronic]. 2005 Dec 12/2/2005; 280(48): 40097-103. PMID: 16199529, PII: M506855200, DOI: 10.1074/jbc.M506855200, ISSN: 0021-9258.

Linggi BE, Brandt SJ, Sun ZW, Hiebert SW. Translating the histone code into leukemia. J. Cell. Biochem. 2005 Dec 12/1/2005; 96(5): 938-50. PMID: 16167339, DOI: 10.1002/jcb.20604, ISSN: 0730-2312.

Amann JM, Chyla BJ, Ellis TC, Martinez A, Moore AC, Franklin JL, McGhee L, Meyers S, Ohm JE, Luce KS, Ouelette AJ, Washington MK, Thompson MA, King D, Gautam S, Coffey RJ, Whitehead RH, Hiebert SW. Mtgr1 is a transcriptional corepressor that is required for maintenance of the secretory cell lineage in the small intestine. Mol. Cell. Biol. 2005 Nov; 25(21): 9576-85. PMID: 16227606, PMCID: PMC1265807, PII: 25/21/9576, DOI: 10.1128/MCB.25.21.9576-9585.2005, ISSN: 0270-7306.

Ice RJ, Wildonger J, Mann RS, Hiebert SW. Comment on "Nervy links protein kinase A to plexin-mediated semaphorin repulsion". Science. 2005 Jul 7/22/2005; 309(5734): 558; author reply 558. PMID: 16040690, PII: 309/5734/558b, DOI: 10.1126/science.1108719, ISSN: 1095-9203.

Yang G, Khalaf W, van de Locht L, Jansen JH, Gao M, Thompson MA, van der Reijden BA, Gutmann DH, Delwel R, Clapp DW, Hiebert SW. Transcriptional repression of the Neurofibromatosis-1 tumor suppressor by the t(8;21) fusion protein. Mol. Cell. Biol. 2005 Jul; 25(14): 5869-79. PMID: 15988004, PMCID: PMC1168824, PII: 25/14/5869, DOI: 10.1128/MCB.25.14.5869-5879.2005, ISSN: 0270-7306.

Yang G, Khalaf W, van de Locht L, Jansen JH, van der Reijden BA, Müller-Tidow C, Delwel HR, Serve H, Clapp DW, Hiebert SW. Epigenetic regulation of tumor suppressors in t(8:21)-containing AML. Ann. Hematol [print-electronic]. 2004 Jun; 83(6): 329-30. PMID: 15052372, DOI: 10.1007/s00277-003-0841-8, ISSN: 0939-5555.

Durst KL, Hiebert SW. Role of RUNX family members in transcriptional repression and gene silencing. Oncogene. 2004 May 5/24/2004; 23(24): 4220-4. PMID: 15156176, PII: 1207122, DOI: 10.1038/sj.onc.1207122, ISSN: 0950-9232.

Müller-Tidow C, Steffen B, Cauvet T, Tickenbrock L, Ji P, Diederichs S, Sargin B, Köhler G, Stelljes M, Puccetti E, Ruthardt M, deVos S, Hiebert SW, Koeffler HP, Berdel WE, Serve H. Translocation products in acute myeloid leukemia activate the Wnt signaling pathway in hematopoietic cells. Mol. Cell. Biol. 2004 Apr; 24(7): 2890-904. PMID: 15024077, PMCID: PMC371102, ISSN: 0270-7306.

Irvin BJ, Hiebert SW. AML-1 steps up to the platelets. Nature medicine. 2004 Mar; 10(3) Sect. 238,9.

Yang G, Khalaf W, van de Locht L, Jansen JH, van der Reijden BA, Müller-Tidow C, Delwel HR, Serve H, Clapp DW, Hiebert SW. Epigenetic regulation of tumor suppressors in t(8:21)-containing AML. Ann. Hematol. 2004; 83 Suppl 1: S83. PMID: 15124686, DOI: 10.1007/s00277-004-0850-2, ISSN: 0939-5555.

Irvin BJ, Wood LD, Wang L, Fenrick R, Sansam CG, Packham G, Kinch M, Yang E, Hiebert SW. TEL, a putative tumor suppressor, induces apoptosis and represses transcription of Bcl-XL. J. Biol. Chem [print-electronic]. 2003 Nov 11/21/2003; 278(47): 46378-86. PMID: 12960174, PII: M305189200, DOI: 10.1074/jbc.M305189200, ISSN: 0021-9258.

Wood LD, Irvin BJ, Nucifora G, Luce KS, Hiebert SW. Small ubiquitin-like modifier conjugation regulates nuclear export of TEL, a putative tumor suppressor. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2003 Mar 3/18/2003; 100(6): 3257-62. PMID: 12626745, PMCID: PMC152279, PII: 0637114100, DOI: 10.1073/pnas.0637114100, ISSN: 0027-8424.

Hiebert SW, Reed-Inderbitzin EF, Amann J, Irvin B, Durst K, Linggi B. The t(8;21) fusion protein contacts co-repressors and histone deacetylases to repress the transcription of the p14ARF tumor suppressor. Blood Cells Mol. Dis. 2003 Mar; 30(2): 177-83. PMID: 12732181, PII: S1079979603000214, ISSN: 1079-9796.

Durst KL, Lutterbach B, Kummalue T, Friedman AD, Hiebert SW. The inv(16) fusion protein associates with corepressors via a smooth muscle myosin heavy-chain domain. Mol. Cell. Biol. 2003 Jan; 23(2): 607-19. PMID: 12509458, PMCID: PMC151524, ISSN: 0270-7306.

Barseguian K, Lutterbach B, Hiebert SW, Nickerson J, Lian JB, Stein JL, van Wijnen AJ, Stein GS. Multiple subnuclear targeting signals of the leukemia-related AML1/ETO and ETO repressor proteins. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2002 Nov 11/26/2002; 99(24): 15434-9. PMID: 12427969, PMCID: PMC137734, PII: 242588499, DOI: 10.1073/pnas.242588499, ISSN: 0027-8424.

de Guzman CG, Warren AJ, Zhang Z, Gartland L, Erickson P, Drabkin H, Hiebert SW, Klug CA. Hematopoietic stem cell expansion and distinct myeloid developmental abnormalities in a murine model of the AML1-ETO translocation. Mol. Cell. Biol. 2002 Aug; 22(15): 5506-17. PMID: 12101243, PMCID: PMC133929, ISSN: 0270-7306.

King D, Yang G, Thompson MA, Hiebert SW. Loss of neurofibromatosis-1 and p19(ARF) cooperate to induce a multiple tumor phenotype. Oncogene. 2002 Jul 7/25/2002; 21(32): 4978-82. PMID: 12118376, DOI: 10.1038/sj.onc.1205632, ISSN: 0950-9232.

Linggi B, Müller-Tidow C, van de Locht L, Hu M, Nip J, Serve H, Berdel WE, van der Reijden B, Quelle DE, Rowley JD, Cleveland J, Jansen JH, Pandolfi PP, Hiebert SW. The t(8;21) fusion protein, AML1 ETO, specifically represses the transcription of the p14(ARF) tumor suppressor in acute myeloid leukemia. Nat. Med [print-electronic]. 2002 Jul; 8(7): 743-50. PMID: 12091906, PII: nm726, DOI: 10.1038/nm726, ISSN: 1078-8956.

Eischen CM, Packham G, Nip J, Fee BE, Hiebert SW, Zambetti GP, Cleveland JL. Bcl-2 is an apoptotic target suppressed by both c-Myc and E2F-1. Oncogene. 2001 Oct 10/25/2001; 20(48): 6983-93. PMID: 11704823, DOI: 10.1038/sj.onc.1204892, ISSN: 0950-9232.

Amann JM, Nip J, Strom DK, Lutterbach B, Harada H, Lenny N, Downing JR, Meyers S, Hiebert SW. ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain. Mol. Cell. Biol. 2001 Oct; 21(19): 6470-83. PMID: 11533236, PMCID: PMC99794, ISSN: 0270-7306.

Hiebert SW, Lutterbach B, Amann J. Role of co-repressors in transcriptional repression mediated by the t(8;21), t(16;21), t(12;21), and inv(16) fusion proteins. Curr. Opin. Hematol. 2001 Jul; 8(4): 197-200. PMID: 11561155, ISSN: 1065-6251.

Wang L, Hiebert SW. TEL contacts multiple co-repressors and specifically associates with histone deacetylase-3. Oncogene. 2001 Jun 6/21/2001; 20(28): 3716-25. PMID: 11439334, DOI: 10.1038/sj.onc.1204479, ISSN: 0950-9232.

Nip J, Strom DK, Eischen CM, Cleveland JL, Zambetti GP, Hiebert SW. E2F-1 induces the stabilization of p53 but blocks p53-mediated transactivation. Oncogene. 2001 Feb 2/22/2001; 20(8): 910-20. PMID: 11314026, DOI: 10.1038/sj.onc.1204171, ISSN: 0950-9232.

Melnick A, Carlile GW, McConnell MJ, Polinger A, Hiebert SW, Licht JD. AML-1/ETO fusion protein is a dominant negative inhibitor of transcriptional repression by the promyelocytic leukemia zinc finger protein. Blood. 2000 Dec 12/1/2000; 96(12): 3939-47. PMID: 11090081, ISSN: 0006-4971.

Fenrick R, Wang L, Nip J, Amann JM, Rooney RJ, Walker-Daniels J, Crawford HC, Hulboy DL, Kinch MS, Matrisian LM, Hiebert SW. TEL, a putative tumor suppressor, modulates cell growth and cell morphology of ras-transformed cells while repressing the transcription of stromelysin-1. Mol. Cell. Biol. 2000 Aug; 20(16): 5828-39. PMID: 10913166, PMCID: PMC86060, ISSN: 0270-7306.

Lutterbach B, Hiebert SW. Role of the transcription factor AML-1 in acute leukemia and hematopoietic differentiation. Gene. 2000 Mar 3/21/2000; 245(2): 223-35. PMID: 10717473, PII: S0378-1119(00)00014-7, ISSN: 0378-1119.

Melnick AM, Westendorf JJ, Polinger A, Carlile GW, Arai S, Ball HJ, Lutterbach B, Hiebert SW, Licht JD. The ETO protein disrupted in t(8;21)-associated acute myeloid leukemia is a corepressor for the promyelocytic leukemia zinc finger protein. Mol. Cell. Biol. 2000 Mar; 20(6): 2075-86. PMID: 10688654, PMCID: PMC110824, ISSN: 0270-7306.

Strom DK, Nip J, Westendorf JJ, Linggi B, Lutterbach B, Downing JR, Lenny N, Hiebert SW. Expression of the AML-1 oncogene shortens the G(1) phase of the cell cycle. J. Biol. Chem. 2000 Feb 2/4/2000; 275(5): 3438-45. PMID: 10652337, ISSN: 0021-9258.

Lutterbach B, Westendorf JJ, Linggi B, Isaac S, Seto E, Hiebert SW. A mechanism of repression by acute myeloid leukemia-1, the target of multiple chromosomal translocations in acute leukemia. J. Biol. Chem. 2000 Jan 1/7/2000; 275(1): 651-6. PMID: 10617663, ISSN: 0021-9258.

Meyers S, Hiebert SW. Alterations in subnuclear trafficking of nuclear regulatory factors in acute leukemia. J. Cell. Biochem. Suppl. 2000; Suppl 35: 93-8. PMID: 11389537, PII: 10.1002/1097-4644(2000)79:35+<93::AID-JCB1131>3.0.CO;2-4, ISSN: 0733-1959.

Nip J, Hiebert SW. Topoisomerase IIalpha mediates E2F-1-induced chemosensitivity and is a target for p53-mediated transcriptional repression. Cell Biochem. Biophys. 2000; 33(2): 199-207. PMID: 11325040, PII: CBB:33:2:199, DOI: 10.1385/CBB:33:2:199, ISSN: 1085-9195.

Lutterbach B, Hou Y, Durst KL, Hiebert SW. The inv(16) encodes an acute myeloid leukemia 1 transcriptional corepressor. Proc. Natl. Acad. Sci. U.S.A. 1999 Oct 10/26/1999; 96(22): 12822-7. PMID: 10536006, PMCID: PMC23113, ISSN: 0027-8424.

Fenrick R, Amann JM, Lutterbach B, Wang L, Westendorf JJ, Downing JR, Hiebert SW. Both TEL and AML-1 contribute repression domains to the t(12;21) fusion protein. Mol. Cell. Biol. 1999 Oct; 19(10): 6566-74. PMID: 10490596, PMCID: PMC84626, ISSN: 0270-7306.

Westendorf JJ, Mernaugh R, Hiebert SW. Identification and characterization of a protein containing formin homology (FH1/FH2) domains. Gene. 1999 May 5/31/1999; 232(2): 173-82. PMID: 10352228, PII: S0378111999001274, ISSN: 0378-1119.

Westendorf JJ, Hiebert SW. Mammalian runt-domain proteins and their roles in hematopoiesis, osteogenesis, and leukemia. J. Cell. Biochem. 1999; Suppl 32-33: 51-8. PMID: 10629103, PII: 10.1002/(SICI)1097-4644(1999)75:32+<51::AID-JCB7>3.0.CO;2-S, ISSN: 0730-2312.

Lutterbach B, Westendorf JJ, Linggi B, Patten A, Moniwa M, Davie JR, Huynh KD, Bardwell VJ, Lavinsky RM, Rosenfeld MG, Glass C, Seto E, Hiebert SW. ETO, a target of t(8;21) in acute leukemia, interacts with the N-CoR and mSin3 corepressors. Mol. Cell. Biol. 1998 Dec; 18(12): 7176-84. PMID: 9819404, PMCID: PMC109299, ISSN: 0270-7306.

Petrovick MS, Hiebert SW, Friedman AD, Hetherington CJ, Tenen DG, Zhang DE. Multiple functional domains of AML1: PU.1 and C/EBPalpha synergize with different regions of AML1. Mol. Cell. Biol. 1998 Jul; 18(7): 3915-25. PMID: 9632776, PMCID: PMC108976, ISSN: 0270-7306.

Lutterbach B, Sun D, Schuetz J, Hiebert SW. The MYND motif is required for repression of basal transcription from the multidrug resistance 1 promoter by the t(8;21) fusion protein. Mol. Cell. Biol. 1998 Jun; 18(6): 3604-11. PMID: 9584201, PMCID: PMC108942, ISSN: 0270-7306.

Ji C, Casinghino S, Chang DJ, Chen Y, Javed A, Ito Y, Hiebert SW, Lian JB, Stein GS, McCarthy TL, Centrella M. CBFa(AML/PEBP2)-related elements in the TGF-beta type I receptor promoter and expression with osteoblast differentiation. J. Cell. Biochem. 1998 Jun 6/1/1998; 69(3): 353-63. PMID: 9581873, PII: 10.1002/(SICI)1097-4644(19980601)69:3<353::AID-JCB12>3.0.CO;2-D, ISSN: 0730-2312.

Fenrick R, Hiebert SW. Role of histone deacetylases in acute leukemia. J. Cell. Biochem. Suppl. 1998; 30-31: 194-202. PMID: 9893271, ISSN: 0733-1959.

Strom DK, Cleveland JL, Chellappan S, Nip J, Hiebert SW. E2F-1 and E2F-3 are functionally distinct in their ability to promote myeloid cell cycle progression and block granulocyte differentiation. Cell Growth Differ. 1998 Jan; 9(1): 59-69. PMID: 9438389, ISSN: 1044-9523.

Westendorf JJ, Yamamoto CM, Lenny N, Downing JR, Selsted ME, Hiebert SW. The t(8;21) fusion product, AML-1-ETO, associates with C/EBP-alpha, inhibits C/EBP-alpha-dependent transcription, and blocks granulocytic differentiation. Mol. Cell. Biol. 1998 Jan; 18(1): 322-33. PMID: 9418879, PMCID: PMC121499, ISSN: 0270-7306.

Westendorf, J. J., Yamamoto, C. M., Lenny, N., Downing, J. R., Selsted, M.E., Hiebert, S. W. The t(8;21) fusion product, AML-1ETO, associates with C/EBP-a inhibits C/EBP-a dependent transcription, and blocks granulocytic differentiation. Mol. Cell. Biol. 1998; 18: 322-33.

Lenny N, Westendorf JJ, Hiebert SW. Transcriptional regulation during myelopoiesis. Mol. Biol. Rep. 1997 Aug; 24(3): 157-68. PMID: 9291089, ISSN: 0301-4851.

Banerjee C, McCabe LR, Choi JY, Hiebert SW, Stein JL, Stein GS, Lian JB. Runt homology domain proteins in osteoblast differentiation: AML3/CBFA1 is a major component of a bone-specific complex. J. Cell. Biochem. 1997 Jul 7/1/1997; 66(1): 1-8. PMID: 9215522, PII: 10.1002/(SICI)1097-4644(19970701)66:1<1::AID-JCB1>3.0.CO;2-V, ISSN: 0730-2312.

Zeng C, van Wijnen AJ, Stein JL, Meyers S, Sun W, Shopland L, Lawrence JB, Penman S, Lian JB, Stein GS, Hiebert SW. Identification of a nuclear matrix targeting signal in the leukemia and bone-related AML/CBF-alpha transcription factors. Proc. Natl. Acad. Sci. U.S.A. 1997 Jun 6/24/1997; 94(13): 6746-51. PMID: 9192636, PMCID: PMC21229, ISSN: 0027-8424.

Nip J, Strom DK, Fee BE, Zambetti G, Cleveland JL, Hiebert SW. E2F-1 cooperates with topoisomerase II inhibition and DNA damage to selectively augment p53-independent apoptosis. Mol. Cell. Biol. 1997 Mar; 17(3): 1049-56. PMID: 9032231, PMCID: PMC231829, ISSN: 0270-7306.

Rhoades KL, Hetherington CJ, Rowley JD, Hiebert SW, Nucifora G, Tenen DG, Zhang DE. Synergistic up-regulation of the myeloid-specific promoter for the macrophage colony-stimulating factor receptor by AML1 and the t(8;21) fusion protein may contribute to leukemogenesis. Proc. Natl. Acad. Sci. U.S.A. 1996 Oct 10/15/1996; 93(21): 11895-900. PMID: 8876234, PMCID: PMC38155, ISSN: 0027-8424.

Meyers S, Lenny N, Sun W, Hiebert SW. AML-2 is a potential target for transcriptional regulation by the t(8;21) and t(12;21) fusion proteins in acute leukemia. Oncogene. 1996 Jul 7/18/1996; 13(2): 303-12. PMID: 8710369, ISSN: 0950-9232.

Banerjee C, Hiebert SW, Stein JL, Lian JB, Stein GS. An AML-1 consensus sequence binds an osteoblast-specific complex and transcriptionally activates the osteocalcin gene. Proc. Natl. Acad. Sci. U.S.A. 1996 May 5/14/1996; 93(10): 4968-73. PMID: 8643513, PMCID: PMC39389, ISSN: 0027-8424.

Hitomi M, Shu J, Strom D, Hiebert SW, Harter ML, Stacey DW. Prostaglandin A2 blocks the activation of G1 phase cyclin-dependent kinase without altering mitogen-activated protein kinase stimulation. J. Biol. Chem. 1996 Apr 4/19/1996; 271(16): 9376-83. PMID: 8621603, ISSN: 0021-9258.

Hiebert SW, Sun W, Davis JN, Golub T, Shurtleff S, Buijs A, Downing JR, Grosveld G, Roussell MF, Gilliland DG, Lenny N, Meyers S. The t(12;21) translocation converts AML-1B from an activator to a repressor of transcription. Mol. Cell. Biol. 1996 Apr; 16(4): 1349-55. PMID: 8657108, PMCID: PMC231119, ISSN: 0270-7306.

Zhang DE, Hetherington CJ, Meyers S, Rhoades KL, Larson CJ, Chen HM, Hiebert SW, Tenen DG. CCAAT enhancer-binding protein (C/EBP) and AML1 (CBF alpha2) synergistically activate the macrophage colony-stimulating factor receptor promoter. Mol. Cell. Biol. 1996 Mar; 16(3): 1231-40. PMID: 8622667, PMCID: PMC231105, ISSN: 0270-7306.

Okuda T, van Deursen J, Hiebert SW, Grosveld G, Downing JR. AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell. 1996 Jan 1/26/1996; 84(2): 321-30. PMID: 8565077, PII: S0092-8674(00)80986-1, ISSN: 0092-8674.

Hiebert SW, Downing JR, Lenny N, Meyers S. Transcriptional regulation by the t(8;21) fusion protein, AML-1/ETO. Curr. Top. Microbiol. Immunol. 1996; 211: 253-8. PMID: 8585956, ISSN: 0070-217X.

Frank R, Zhang J, Uchida H, Meyers S, Hiebert SW, Nimer SD. The AML1/ETO fusion protein blocks transactivation of the GM-CSF promoter by AML1B. Oncogene. 1995 Dec 12/21/1995; 11(12): 2667-74. PMID: 8545124, ISSN: 0950-9232.

Hiebert SW, Packham G, Strom DK, Haffner R, Oren M, Zambetti G, Cleveland JL. E2F-1:DP-1 induces p53 and overrides survival factors to trigger apoptosis. Mol. Cell. Biol. 1995 Dec; 15(12): 6864-74. PMID: 8524253, PMCID: PMC230941, ISSN: 0270-7306.

Lenny N, Meyers S, Hiebert SW. Functional domains of the t(8;21) fusion protein, AML-1/ETO. Oncogene. 1995 Nov 11/2/1995; 11(9): 1761-9. PMID: 7478604, ISSN: 0950-9232.

Shurtleff SA, Meyers S, Hiebert SW, Raimondi SC, Head DR, Willman CL, Wolman S, Slovak ML, Carroll AJ, Behm F. Heterogeneity in CBF beta/MYH11 fusion messages encoded by the inv(16)(p13q22) and the t(16;16)(p13;q22) in acute myelogenous leukemia. Blood. 1995 Jun 6/15/1995; 85(12): 3695-703. PMID: 7780153, ISSN: 0006-4971.

Golub TR, Barker GF, Bohlander SK, Hiebert SW, Ward DC, Bray-Ward P, Morgan E, Raimondi SC, Rowley JD, Gilliland DG. Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia. Proc. Natl. Acad. Sci. U.S.A. 1995 May 5/23/1995; 92(11): 4917-21. PMID: 7761424, PMCID: PMC41818, ISSN: 0027-8424.

Meyers S, Lenny N, Hiebert SW. The t(8;21) fusion protein interferes with AML-1B-dependent transcriptional activation. Mol. Cell. Biol. 1995 Apr; 15(4): 1974-82. PMID: 7891692, PMCID: PMC230424, ISSN: 0270-7306.

Meyers S, Hiebert SW. Indirect and direct disruption of transcriptional regulation in cancer: E2F and AML-1. Crit. Rev. Eukaryot. Gene Expr. 1995; 5(3-4): 365-83. PMID: 8834231, ISSN: 1045-4403.

Dobrowolski SF, Stacey DW, Harter ML, Stine JT, Hiebert SW. An E2F dominant negative mutant blocks E1A induced cell cycle progression. Oncogene. 1994 Sep; 9(9): 2605-12. PMID: 8058324, ISSN: 0950-9232.

Roussel MF, Davis JN, Cleveland JL, Ghysdael J, Hiebert SW. Dual control of myc expression through a single DNA binding site targeted by ets family proteins and E2F-1. Oncogene. 1994 Feb; 9(2): 405-15. PMID: 8290253, ISSN: 0950-9232.

Meyers S, Downing JR, Hiebert SW. Identification of AML-1 and the (8;21) translocation protein (AML-1/ETO) as sequence-specific DNA-binding proteins: the runt homology domain is required for DNA binding and protein-protein interactions. Mol. Cell. Biol. 1993 Oct; 13(10): 6336-45. PMID: 8413232, PMCID: PMC364692, ISSN: 0270-7306.

Hiebert SW. Regions of the retinoblastoma gene product required for its interaction with the E2F transcription factor are necessary for E2 promoter repression and pRb-mediated growth suppression. Mol. Cell. Biol. 1993 Jun; 13(6): 3384-91. PMID: 8497257, PMCID: PMC359800, ISSN: 0270-7306.

Kato J, Matsushime H, Hiebert SW, Ewen ME, Sherr CJ. Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4. Genes Dev. 1993 Mar; 7(3): 331-42. PMID: 8449399, ISSN: 0890-9369.

Roussel MF, Davis JN, Cleveland JL, Hiebert SW. Duel Control of myc Expression Through a Single DNA Binding Site targeted by ets Family Proteins and E2F-1. Oncogene. 1993; 9: 405-15.

Hiebert SW, Chellappan SP, Horowitz JM, Nevins JR. The interaction of RB with E2F coincides with an inhibition of the transcriptional activity of E2F. Genes Dev. 1992 Feb; 6(2): 177-85. PMID: 1531329, ISSN: 0890-9369.

Hiebert SW, Blake M, Azizkhan J, Nevins JR. Role of E2F transcription factor in E1A-mediated trans activation of cellular genes. J. Virol. 1991 Jul; 65(7): 3547-52. PMID: 1828272, PMCID: PMC241350, ISSN: 0022-538X.

Mudryj M, Devoto SH, Hiebert SW, Hunter T, Pines J, Nevins JR. Cell cycle regulation of the E2F transcription factor involves an interaction with cyclin A. Cell. 1991 Jun 6/28/1991; 65(7): 1243-53. PMID: 1829647, PII: 0092-8674(91)90019-U, ISSN: 0092-8674.

Mudryj M, Hiebert SW, Nevins JR. A role for the adenovirus inducible E2F transcription factor in a proliferation dependent signal transduction pathway. EMBO J. 1990 Jul; 9(7): 2179-84. PMID: 2141565, PMCID: PMC551940, ISSN: 0261-4189.

Ng DT, Hiebert SW, Lamb RA. Different roles of individual N-linked oligosaccharide chains in folding, assembly, and transport of the simian virus 5 hemagglutinin-neuraminidase. Mol. Cell. Biol. 1990 May; 10(5): 1989-2001. PMID: 2183015, PMCID: PMC360545, ISSN: 0270-7306.

Hiebert SW, Lipp M, Nevins JR. E1A-dependent trans-activation of the human MYC promoter is mediated by the E2F factor. Proc. Natl. Acad. Sci. U.S.A. 1989 May; 86(10): 3594-8. PMID: 2524830, PMCID: PMC287184, ISSN: 0027-8424.

Hiebert SW, Lamb RA. Cell surface expression of glycosylated, nonglycosylated, and truncated forms of a cytoplasmic protein pyruvate kinase. J. Cell Biol. 1988 Sep; 107(3): 865-76. PMID: 3047152, PMCID: PMC2115283, ISSN: 0021-9525.

Hiebert SW, Richardson CD, Lamb RA. Cell surface expression and orientation in membranes of the 44-amino-acid SH protein of simian virus 5. J. Virol. 1988 Jul; 62(7): 2347-57. PMID: 2836617, PMCID: PMC253391, ISSN: 0022-538X.

Hiebert SW, Williams MA, Lamb RA. Nucleotide sequence of RNA segment 7 of influenza B/Singapore/222/79: maintenance of a second large open reading frame. Virology. 1986 Dec; 155(2): 747-51. PMID: 3788064, ISSN: 0042-6822.

Paterson RG, Hiebert SW, Lamb RA. Expression at the cell surface of biologically active fusion and hemagglutinin/neuraminidase proteins of the paramyxovirus simian virus 5 from cloned cDNA. Proc. Natl. Acad. Sci. U.S.A. 1985 Nov; 82(22): 7520-4. PMID: 3865176, PMCID: PMC390848, ISSN: 0027-8424.

Hiebert SW, Paterson RG, Lamb RA. Identification and predicted sequence of a previously unrecognized small hydrophobic protein, SH, of the paramyxovirus simian virus 5. J. Virol. 1985 Sep; 55(3): 744-51. PMID: 4020965, PMCID: PMC255058, ISSN: 0022-538X.

Hiebert SW, Paterson RG, Lamb RA. Hemagglutinin-neuraminidase protein of the paramyxovirus simian virus 5: nucleotide sequence of the mRNA predicts an N-terminal membrane anchor. J. Virol. 1985 Apr; 54(1): 1-6. PMID: 3973974, PMCID: PMC254752, ISSN: 0022-538X.