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Barbara Hoffman, PhDBarbara 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

 

Educational Background:

 

MS and PhD, Human Genetics, University of Michigan School of Medicine, Ann Arbor, MI

 

Postdoctoral NIH Fellowship, Genetics, Weizmann Institute of Science, Rehovoth, Israel

 

Postdoctoral Fellowship in Genetics, Stanford University School of Medicine, Stanford, CA

 

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Research Interests:

 

The overarching theme of my laboratory is to understand how normal cells are converted to cancer cells, using both leukemia and breast cancer as model systems. For much of my scientific career I focused on hematopoiesis and leukemia as a paradigm for studying malignancy; and for the last ten years have incorporated breast carcinogenesis into my research. My lab studies regulation of proliferation, differentiation and apoptosis using both normal and leukemic/cancer cells, including cell lines, animal models and primary human cells.


Extensive analysis has been done of both positive and negative regulators of myeloid differentiation, to understand normal hematopoiesis as well as how blocks in differentiation and apoptosis participate in the initiation and progression of leukemia. We have shown how deregulated expression of negative regulators of differentiation, including c-Myc, c-Myb and E2F-1, blocked differentiation, and have extensively studied how deregulated c-Myc prematurely activated an apoptotic response in addition to blocking differentiation. Several exciting publications describe our studies on Early Growth Response Gene (Egr)-1 promoting myeloid differentiation, and overriding the block in differentiation due to deregulated E2F-1 or c-Myc, thereby demonstrating tumor suppressor functions.


The stress response gene family Gadd45 has become a focal point over the last several years, understanding how it works at the molecular and cellular level, and what its role is in response to stress. Within the last 5 years my laboratory has studied the role of gadd45 in response to oncogenic stress, using breast cancer and leukemia mouse models. More recently my laboratory has started to extensively utilize bone marrow transplantation (BMT) to further analyze the effect of stress response/tumor suppressor Egr-1 and the stress response Gadd45 family of genes on leukemia initiation and progression.


Translational studies incorporate human tumor tissue as well as xenograft mouse models with human tumor cells/cell lines. These lines of inquiry include investigating expression of genes of interest and their downstream effectors, as well as functional studies with these players. Response to known drugs, separately and in combination, will also be incorporated into the research plan. Knowledge acquired from analysis of human tissue and response to drugs has the potential to identify players that can impact on the aggressiveness of disease, and predict outcome for currently established therapies, as well as provide information to design novel targeted treatment regimens or adjunct therapy in conjunction with available treatments

 

Hoffman figure 1

Hoffman figure 2

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PUBMED PUBLICATIONS :


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

24104471. Hoffman B, Liebermann DA, Gadd45 in modulation of solid tumors and leukemia. Adv Exp Med Biol 793:(21-33)2013

22802593. Leach PT, Poplawski SG, Kenney JW, Hoffman B, Liebermann DA, Abel T, Gould TJ, Gadd45b knockout mice exhibit selective deficits in hippocampus-dependent long-term memory. Learn Mem 19:8(319-24)2012 Jul 16

22718299. Xiong Y, Liebermann DA, Holtzman EJ, Jeronis S, Hoffman B, Geifman-Holtzman O, Preeclampsia-associated stresses activate Gadd45a signaling and sFlt-1 in placental explants. J Cell Physiol 228:2(362-70)2013 Feb

22307729. Salerno DM, Tront JS, Hoffman B, Liebermann DA, Gadd45a and Gadd45b modulate innate immune functions of granulocytes and macrophages by differential regulation of p38 and JNK signaling. J Cell Physiol 227:11(3613-20)2012 Nov

22150313. Liebermann DA, Tront JS, Sha X, Mukherjee K, Mohamed-Hadley A, Hoffman B, Gadd45 stress sensors in malignancy and leukemia. Crit Rev Oncog 16:1-2(129-40)2011

21098706. Tront JS, Huang Y, Fornace AJ Jr, Hoffman B, Liebermann DA, Gadd45a functions as a promoter or suppressor of breast cancer dependent on the oncogenic stress. Cancer Res 70:23(9671-81)2010 Dec 1

20642319. Geifman-Holtzman O, Xiong Y, Holtzman EJ, Hoffman B, Gaughan J, Liebermann DA, Increased placental telomerase mRNA in hypertensive disorders of pregnancy. Hypertens Pregnancy 29:4(434-45)2010

19834918. Zumbrun SD, Hoffman B, Liebermann DA, Distinct mechanisms are utilized to induce stress sensor gadd45b by different stress stimuli. J Cell Biochem 108:5(1220-31)2009 Dec 1

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 16

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

14982872. Shafarenko M, Amanullah A, Gregory B, Liebermann DA, Hoffman B, Fos modulates myeloid cell survival and differentiation and partially abrogates the c-Myc block in terminal myeloid differentiation. Blood 103:11(4259-67)2004 Jun 1

12972029. Liebermann DA, Hoffman B, Myeloid differentiation (MyD) primary response genes in hematopoiesis. Blood Cells Mol Dis 31:2(213-28)2003 Sep-Oct

12932304. Balliet AG, Hollander MC, Fornace AJ Jr, Hoffman B, Liebermann DA, Comparative analysis of the genetic structure and chromosomal mapping of the murine Gadd45g/CR6 gene. DNA Cell Biol 22:7(457-68)2003 Jul

12917673. Amanullah A, Azam N, Balliet A, Hollander C, Hoffman B, Fornace A, Liebermann D, Cell signalling: cell survival and a Gadd45-factor deficiency. Nature 424:6950(741; discussion 742)2003 Aug 14

12351382. Rane SG, Mangan JK, Amanullah A, Wong BC, Vora RK, Liebermann DA, Hoffman B, Graņa X, Reddy EP, Activation of the Jak3 pathway is associated with granulocytic differentiation of myeloid precursor cells. Blood 100:8(2753-62)2002 Oct 15

12124778. Vairapandi M, Balliet AG, Hoffman B, Liebermann DA, GADD45b and GADD45g are cdc2/cyclinB1 kinase inhibitors with a role in S and G2/M cell cycle checkpoints induced by genotoxic stress. J Cell Physiol 192:3(327-38)2002 Sep

12070012. Sjin RM, Krishnaraju K, Hoffman B, Liebermann DA, Transcriptional regulation of myeloid differentiation primary response (MyD) genes during myeloid differentiation is mediated by nuclear factor Y. Blood 100:1(80-8)2002 Jul 1

12032779. Hoffman B, Amanullah A, Shafarenko M, Liebermann DA, The proto-oncogene c-myc in hematopoietic development and leukemogenesis. Oncogene 21:21(3414-21)2002 May 13

12032777. Liebermann DA, Hoffman B, Myeloid differentiation (MyD) primary response genes in hematopoiesis. Oncogene 21:21(3391-402)2002 May 13

11960329. Liebermann DA, Hoffman B, Myeloid differentiation (MyD)/growth arrest DNA damage (GADD) genes in tumor suppression, immunity and inflammation. Leukemia 16:4(527-41)2002 Apr

11896589. Amanullah A, Liebermann DA, Hoffman B, Deregulated c-Myc prematurely recruits both Type I and II CD95/Fas apoptotic pathways associated with terminal myeloid differentiation. Oncogene 21:10(1600-10)2002 Feb 28

11403721. Balliet AG, Hatton KS, Hoffman B, Liebermann DA, Comparative analysis of the genetic structure and chromosomal location of the murine MyD118 (Gadd45beta) gene. DNA Cell Biol 20:4(239-47)2001 Apr

11251170. Zhang W, Hoffman B, Liebermann DA, Ectopic expression of MyD118/Gadd45/CR6 (Gadd45beta/alpha/gamma) sensitizes neoplastic cells to genotoxic stress-induced apoptosis. Int J Oncol 18:4(749-57)2001 Apr

11222373. Krishnaraju K, Hoffman B, Liebermann DA, Early growth response gene 1 stimulates development of hematopoietic progenitor cells along the macrophage lineage at the expense of the granulocyte and erythroid lineages. Blood 97:5(1298-305)2001 Mar 1

11022036. Azam N, Vairapandi M, Zhang W, Hoffman B, Liebermann DA, Interaction of CR6 (GADD45gamma ) with proliferating cell nuclear antigen impedes negative growth control. J Biol Chem 276:4(2766-74)2001 Jan 26

10967552. Vairapandi M, Liebermann DA, Hoffman B, Duker NJ, Human DNA-demethylating activity: a glycosylase associated with RNA and PCNA. J Cell Biochem 79:2(249-60)2000 Aug 2

10887108. Amanullah A, Hoffman B, Liebermann DA, Deregulated E2F-1 blocks terminal differentiation and loss of leukemogenicity of M1 myeloblastic leukemia cells without abrogating induction of p15(INK4B) and p16(INK4A). Blood 96:2(475-82)2000 Jul 15

10871848. Amanullah A, Liebermann DA, Hoffman B, p53-independent apoptosis associated with c-Myc-mediated block in myeloid cell differentiation. Oncogene 19:26(2967-77)2000 Jun 15

10828887. Bernardi R, Liebermann DA, Hoffman B, Cdc25A stability is controlled by the ubiquitin-proteasome pathway during cell cycle progression and terminal differentiation. Oncogene 19:20(2447-54)2000 May 11

10828065. Vairapandi M, Azam N, Balliet AG, Hoffman B, Liebermann DA, Characterization of MyD118, Gadd45, and proliferating cell nuclear antigen (PCNA) interacting domains. PCNA impedes MyD118 AND Gadd45-mediated negative growth control. J Biol Chem 275:22(16810-9)2000 Jun 2

10497240. Sjin RM, Lord KA, Abdollahi A, Hoffman B, Liebermann DA, Interleukin-6 and leukemia inhibitory factor induction of JunB is regulated by distinct cell type-specific cis-acting elements. J Biol Chem 274:40(28697-707)1999 Oct 1

10490824. Zhang W, Bae I, Krishnaraju K, Azam N, Fan W, Smith K, Hoffman B, Liebermann DA, CR6: A third member in the MyD118 and Gadd45 gene family which functions in negative growth control. Oncogene 18:35(4899-907)1999 Sep 2

9916997. Hoffman B, Liebermann DA, The proto-oncogene c-myc and apoptosis. Oncogene 17:25(3351-7)1998 Dec 24

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