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Dan Liebermann., PhD

Professor, Biochemistry

Professor, Fels Institute for Cancer Research and Molecular Biology

Telephone:  215-707- 6903

Fax:  215-707-2805

Email: lieberma@temple.edu

Department of Biochemistry

Fels Institute for Cancer Research and Molecular Biology

B.Sc./prMD - Tel Aviv University, Israel

PhD Molecular Genetics - Weizmann Institute, Israel

Postdoctoral Fellow - Stanford University School of Medicine

Assistant Professor - University of Pennsylvania School of Medicine

Professor - Temple University School of Medicine, Fels Institute and Department of Biochemistry

 

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The overall goal of the research is aimed at understanding the molecular biology of normal cell growth and differentiation and the breakdown in normal controls that occur upon initiation and progression of cancer, including the role of oncogene and tumor-suppressor genes. Ultimately, the goal is to use such genes & gene products as molecular genetic tools to employ novel "gene therapy" for the treatment of leukemias and other malignancies--notably breast cancer.  We are particularly interested in gaining a better understanding of the molecular-genetic controls of normal hematopoiesis and leukemogenesis and genetic determinants that contribute to breast carcinogenesis. Towards this goal several interesting ongoing research projects include:

Deciphering the role of novel myeloid Differentiation (MyD) primary response genes/ Growth Arrest DNA Damage (GADD) genes, termed MyD118/ Gadd45b, CR6/ Gadd45g , Gadd45/Gadd45a , in activation of G1/S and G2/M cell cycle checkpoints, cell survival, DNA repair or cell death in response to genotoxic stress agents (such as anti-cancer agents), and in control of normal cell homeostasis as opposed to in leukemogenicity/breast carcinogenesis. This research line takes advantage of recently established knockout mouse models which are deficient for one or more of these MyD/Gadd genes and are transgenic for cancer susceptibility oncogenes such as deregulated c-myc or activated H-ras.

The hypothesis tested is that the nature/magnitude of stress dictates which partners Gadd45 proteins will associate with to signal cell survival or cell death. In response to low stress, Gadd45 proteins may interact with p21, cdc2/cyclinB1 & PCNA to activate cell cycle arrest and DNA repair, ultimately promoting cell survival, whereas in response to high stress, including cellular aging & activated oncogenes, Gadd45 proteins may interact with stress kinases (MEKK4, p38, JNK) to promote apoptosis or senescence. It is surmised that stress sensing functions of Gadd45 proteins play a role in modulating tumor formation.

In collaboration with Dr Barbara Hoffman's group we are also investigating the nature of molecular interactions between negative regulators of terminal differentiation (Myc, Myb, E2F), that when deregulated block the terminal differentiation program, and positive regulators (Egr-1, gadd45 genes) in controling normal cell development and in tumor suppression.

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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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