
Scott W. Hiebert, Ph.D.
- Associate Director for Shared Resources
- Associate Director for Research Education
- Hortense B. Ingram Professor of Cancer Research
- Professor of Biochemistry
- Associate Professor of Medicine
Phone
512 Preston Building
Nashville, TN 37232-6838
Scott W. Hiebert, Ph.D.
- Associate Director for Shared Resources
- Associate Director for Research Education
- Hortense B. Ingram Professor of Cancer Research
- Professor of Biochemistry
- Associate Professor of Medicine
615-936-3582
scott.hiebert@vanderbilt.edu
512 Preston Building
Nashville, TN 37232-6838
Research Program
Departments/Affiliations
Profile
Education
Research Emphasis
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
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.
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.