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Barbara Hoffman , PhD

Professor, Biochemistry

Professor, Fels Institute for Cancer Research and Molecular Biology

Telephone:  215-707-6902

Fax:  215-707-2805

Email: hoffman@temple.edu

Department of Biochemistry

Fels Institute for Cancer Research and Molecular Biology

University of Michigan School of Medicine

 

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My laboratory studies the molecular-genetic controls regulating cell growth, differentiation, and survival, and the breakdown in these controls that result in tumor production. Mouse models, normal cells and cell lines are routinely used for these investigations.

The proto-oncogene c-myc is a positive regulator of proliferation and apoptosis and a negative regulator of terminal differentiation. Deregulated expression of c-myc blocks white blood cell differentiation and allows cells to proliferate indefinitely while undergoing apoptosis; this provides a model system to study terminal differentiation as well as leukemogenesis and the progression to more aggressive leukemias. Studies with additional negative regulators of differentiation, including c-myb and E2F, expand this area of investigation.

This laboratory has identified primary response genes (MyD) that are activated in the absence of de novo protein synthesis when myeloid differentiation is induced. Several of these genes have been demonstrated to be positive regulators of differentiation, growth arrest, and/or apoptosis, including IRF-1, fos/jun, and Egr-1, as well as MyD118, MyD116 and. MyD88. The effect of positive regulators of differentiation, separately as well as in combination with negative regulators, on myeloid development and tumor formation is being investigated. The positive regulator Egr-1 overrides the blocks in differentiation imparted by c-myc, c-myb and E2F, and behaves as a tumor suppressor. These observations open many avenues of inquiry about molecular switches regulating differentiation and how blocks in differentiation promote tumor development.

We have shown that the ubiquitous transcription factor NF-Y participates in MyD gene induction during myeloid differentiation, and may also be involved in the coupling of proliferation to terminal differentiation during normal myeloid development. How NF-Y is regulated and modified during myeloid development, and regulates MyD gene expression will be determined.

The MyD118/CR6/Gadd45 gene family, shown to be negative growth regulators and potential tumor suppressors, is also a major focal point of study, both in the context of hematopoiesis, as well as in other cell models during development, in response to stress, and in tumor formation.

Understanding how alterations in the expression and/or function of regulators of growth, differentiation and survival affect normal development, will contribute to a greater understanding of the genetic events involved in the evolution of tumors.

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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

19834918. Zumbrun SD, Hoffman B, Liebermann DA, Distinct mechanisms are utilized to induce stress sensor gadd45b by different stress stimuli. J Cell Biochem :()2009 Oct 15

19652693. Cretu A, Sha X, Tront J, Hoffman B, Liebermann DA, Stress sensor Gadd45 genes as therapeutic targets in cancer. Cancer Ther 7:A(268-276)2009

19452502. Xiong Y, Liebermann DA, Tront JS, Holtzman EJ, Huang Y, Hoffman B, Geifman-Holtzman O, Gadd45a stress signaling regulates sFlt-1 expression in preeclampsia. J Cell Physiol 220:3(632-9)2009 Sep

19229137. Engel N, Tront JS, Erinle T, Nguyen N, Latham KE, Sapienza C, Hoffman B, Liebermann DA, Conserved DNA methylation in Gadd45a(-/-) mice. Epigenetics 4:2(98-9)2009 Feb

18955973. Hoffman B, Liebermann DA, Apoptotic signaling by c-MYC. Oncogene 27:50(6462-72)2008 Oct 27

18789159. Liebermann DA, Hoffman B, Gadd45 in stress signaling. J Mol Signal 3:(15)2008 Sep 12

18780287. Hoffman B, Liebermann DA, Gadd45 modulation of intrinsic and extrinsic stress responses in myeloid cells. J Cell Physiol 218:1(26-31)2009 Jan

18650844. Gibbs JD, Liebermann DA, Hoffman B, Leukemia suppressor function of Egr-1 is dependent on transforming oncogene. Leukemia 22:10(1909-16)2008 Oct

18247372. D'Angelo S, Liebermann D, Hoffman B, The c-myc apoptotic response is not intrinsic to blocking terminal myeloid differentiation. J Cell Physiol 216:1(120-7)2008 Jul

17686638. Hoffman B, Liebermann DA, Role of gadd45 in myeloid cells in response to hematopoietic stress. Blood Cells Mol Dis 39:3(344-7)2007 Nov-Dec

17659913. Liebermann DA, Hoffman B, Gadd45 in the response of hematopoietic cells to genotoxic stress. Blood Cells Mol Dis 39:3(329-35)2007 Nov-Dec

17599039. Gibbs JD, Liebermann DA, Hoffman B, Egr-1 abrogates the E2F-1 block in terminal myeloid differentiation and suppresses leukemia. Oncogene 27:1(98-106)2008 Jan 3

17495532. Gibbs JD, Liebermann DA, Hoffman B, Terminal myeloid differentiation is uncoupled from cell cycle arrest. Cell Cycle 6:10(1205-9)2007 May 15

17264673. Liebermann DA, Hoffman B, Vesely D, p53 induced growth arrest versus apoptosis and its modulation by survival cytokines. Cell Cycle 6:2(166-70)2007 Jan 15

17099722. Vesely DL, Hoffman B, Liebermann DA, Phosphatidylinositol 3-kinase/Akt signaling mediates interleukin-6 protection against p53-induced apoptosis in M1 myeloid leukemic cells. Oncogene 26:21(3041-50)2007 May 10

16951155. Tront JS, Hoffman B, Liebermann DA, Gadd45a suppresses Ras-driven mammary tumorigenesis by activation of c-Jun NH2-terminal kinase and p38 stress signaling resulting in apoptosis and senescence. Cancer Res 66:17(8448-54)2006 Sep 1

16732331. Gupta SK, Gupta M, Hoffman B, Liebermann DA, Hematopoietic cells from gadd45a-deficient and gadd45b-deficient mice exhibit impaired stress responses to acute stimulation with cytokines, myeloablation and inflammation. Oncogene 25:40(5537-46)2006 Sep 7

16636063. Gupta M, Gupta SK, Hoffman B, Liebermann DA, Gadd45a and Gadd45b protect hematopoietic cells from UV-induced apoptosis via distinct signaling pathways, including p38 activation and JNK inhibition. J Biol Chem 281:26(17552-8)2006 Jun 30

16170381. Gupta M, Gupta SK, Balliet AG, Hollander MC, Fornace AJ, Hoffman B, Liebermann DA, Hematopoietic cells from Gadd45a- and Gadd45b-deficient mice are sensitized to genotoxic-stress-induced apoptosis. Oncogene 24:48(7170-9)2005 Nov 3

15840692. Shafarenko M, Liebermann DA, Hoffman B, Egr-1 abrogates the block imparted by c-Myc on terminal M1 myeloid differentiation. Blood 106:3(871-8)2005 Aug 1

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