Eldad Zacksenhaus

Research Synopsis

We are using mouse models, cell and molecular biology and bioinformatics to identify mechanisms of cancer initiation, progression and metastasis, that can be exploited for novel therapy.  We focus on breast and brain cancers, the tumor suppressors Rb, Pten and p53 as well as the HER2 oncogene. We are also studying the effect of the Rb pathway on aging.  

Selected current projects:

• TICs and therapeutic targets in Claudin-low triple-negative breast cancer.
• Transposon-mediated mutagenesis to identify oncogenic networks that drive   metastasis in triple-negative breast cancer.
• Therapeutic targeting of HER2+ breast cancer.
• Development and clinical utility of a prognostic signature for HER2+:ERa-negative breast cancer.
•  Rb-p53 pathways in Medulloblastoma: mouse models and therapeutic targeting.
• Control of  skeletal myogenesis by Rb tumor suppressor.
• Regulation of homeostasis and aging by pRb in vivo.  

Selected Publications

Bremner R. and Zacksenhaus E. Cyclins, Cdks, E2f, Skp2 and More at the First International RB Tumor Suppressor Meeting. (2010) Cancer Res. 70(15):6114–6118.

Jiang Z., Jones R., Deng T., Li H., Herschkowitz J.I., Liu J.C., Weigman V.J., Tsao M.-S., Lane T.F., C.M. Perou, and Zacksenhaus E. Rb deletion in mouse mammary progenitors induces luminal-B or basal-like/EMT tumor subtypes depending on p53 status. Journal of Clinical Investigation. (2010) 120(9):3296-309.

Ciavarra G and Zacksenhaus E. Rescue of myogenic defects in Rb-deficient cells by inhibition of autophagy or by hypoxia-induced glycolytic shift. J. Cell Biol. (2010) 191(2):291–301. Audio podcast interview with EZ on the Oct 18 issue of JCB.

Ciavarra G., Ho A.T, Cobrinik D., and Zacksenhaus E. Critical role of the Rb family in myoblast survival and fusion. PLoS One. (2011) 6(3):e17682.

Adams J.R., Xu K., Liu J.C., Agamez N.M., Loch A.J., Wong R.G., Wang W., Wright K.L., Lane T.F., Zacksenhaus E., Egan S.E. Cooperation between Pik3ca and p53 mutations in mouse mammary tumor formation. Cancer Res. (2011) 71(7):2706–2717

Ciavarra G. and Zacksenhaus E. Direct and indirect effects of the pRb tumor suppressor on Autophagy. Autophagy. (2011) 7(5):544–546.

Jiang Z., Jones R., Liu J.C., Deng T., Robinson T., Chung P.E.D., Wang S., Herschkowitz J.I., Egan S.E., Perou C.M., and Zacksenhaus E. RB1 and p53 at the crossroad of EMT and triple-negative breast cancer. Cell Cycle. (2011) 10(10):1563–1570.

Ciavarra G. and Zacksenhaus E. Multiple pathways counteract cell death induced by Rb1 loss: Implications for cancer. Cell Cycle. (2011) 10(10):1533–1539.

Adams J.R., Schachter N., Liu J.C., Zacksenhaus E., and Egan S.E. Elevated PI3K signaling drives multiple Breast Cancer subtypes. Oncotarget. (2011) 2(6):435–447.

Xu K., Usary J., Kousis P.C., Prat A., Wang D.-Y., Adams J.R., Wang W., Loch A.J., Deng T., Zhao W., Cardiff R.D., Yoon K., Gaiano N., Ling V., Beyene J., Zacksenhaus E., Gridley T., Leong W.L., Guidos C.J., Perou C.M., and Egan S.E. Lunatic Fringe Deficiency Cooperates with the Met/Caveolin Gene Amplicon to Induce Basal-like Breast Cancer. Cancer Cell. (2012) 21(5):626–641.

Liu J.C., Voisin V., Badar G.D., Deng T., Pusztai L., Symmans W.F., Esteva F.J., Egan S.E., and Zacksenhaus E. Seventeen-gene Signature from Enriched Her2/Neu Mammary Tumor-Initiating Cells Predicts Clinical Outcome for Human HER2+:ERa- Breast Cancer. Proc. Natl. Acad. Sci. U S A. (2012) 109(15):5832–5837.

Klionsky D.J. et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy (2012) 8(4): 445–544.

Robinson TJ, Liu JC, Vizeacoumar F, Sun T, Egan SE, Schimmer A, Datti A, and Zacksenhaus E. RB1 status in triple negative breast cancer cells dictates response to radiation treatment and selective therapeutic drugs. PLoS One. 2013 Nov 12;8(11):e78641.

Rushlow D.E., Kennett J.Y., Mol B.M., Yee S., Pajovic S., Thériault B.L., Prigoda-Lee N.L., Spencer C., Dimaras H., Corson T.W., Pang R., Massey C., Godbout R., Jiang Z., Zacksenhaus E., Paton K., Moll A.C., Houdayer C., Raizis A., Halliday W., Lam W.L., Boutros P.C., Lohmann D., Dorsman J.C., and Gallie B.L. Not Knudson’s Retinoblastoma: One-Hit Cancer Initiated by the MYCN Oncogene. Lancet Oncology. 2013 Apr;14(4):327-34.

Li Y-J, Liu G, Li Y, Liu JC, Zacksenhaus E, Wan Shan S, Yang BB, Dash R, Fisher PB, Archer MC, and Ben-David Y. IL-24 inhibits growth of breast cancer cells through up-regulation of growth arrest-specific gene 3 (Gas3) and disruption of β1 integrin function. Mol Cancer Res. 2013 Jun;11(6):593-603

Liu JC, Egan SE, and Zacksenhaus E. A tumor initiating cell-derived prognostic signature for HER2+:ERα- breast cancer; rationale, new features, controversies and future directions. Oncotarget. 2013 Aug;4(8):1317-28.

Cai EP, Wu X, Schroer SA, Elia AJ, Nostro MC, Zacksenhaus E, Woo M. Retinoblastoma tumor suppressor protein in pancreatic progenitors controls α- and β-cell fate. Proc Natl Acad Sci U S A. 2013 Sep 3;110(36):14723-8.

Robinson TJ, Pai M, Liu JC, Vizeacoumar F, Sun T, Egan SE, Datti A, Huang J, and Zacksenhaus E. High-throughput screen identifies disulfiram as a potential therapeutic for triple-negative breast cancer cells: interaction with IQ motif-containing factors. Cell Cycle, 2013 Sep 15;12(18):3013-24.

Deng T, Liu JC, Chung PE, Uehling D, Aman A, Joseph B, Ketela T, Jiang Z, Schachter NF, Rottapel R, Egan SE, Al-Awar R, Moffat J, Zacksenhaus E. shRNA kinome screen identifies TBK1 as a therapeutic target for HER2+ breast cancer. Cancer Res. 2014 Jan 31. [Epub ahead of print]

Cai EP, Wu X, Zacksenhaus E, Woo M. Timing is everything: Rb’s choice in islet-cell fate. (Editorial). Cell Cycle. 2014 Feb 14:13(6)

Li Y, Luo H, Liu T, Zacksenhaus E, Ben-David Y. Oncogene. The ets transcription factor Fli-1 in development, cancer and disease. 2014 Jun 9. doi: 10.1038/onc.2014.162. [Epub ahead of print]

Jiang Z, Liu JC, Chung P, Egan SE, Zacksenhaus E. Targeting HER2+ breast cancer: The TBK1/IKKe axis. Invited Perspective - Oncoscience.. 2014 Mar 6;1(2):180-2.

Dembowy J, Adissu HA, Liu JC, Zacksenhaus E, and Woodgett JR. Physiological effects of GSK-3 deletion on mouse mammary gland development and oncogenesis. Oncogene. 2014 Sep 8. [Epub ahead of print].

Cai EP, Luk CT, Wu X, Schroer SA, Shi SY, Sivasubramaniyam T, Brunt JJ, Zacksenhaus E, Woo M.  . Rb and p107 are required for alpha cell survival, beta cell cycle control and glucagon-like peptide-1 action. Diabetologia. 2014 Sep 24. [Epub ahead of print]

Liu JC, Voisin V, Wang S, Lehal R, Wang D-Y, Datti A, Uehling D, Al-awar R, Egan SE, Bader GD, Tsao M, Mak TW, Zacksenhaus E. Combined deletion of murine Pten and p53 induces mammary tumors with dependency on eEF2K. EMBO Molecular Medicine. 2014 Oct 20;6(12):1542-60

Li Y, Luo H, Liu T, Zacksenhaus E, Ben-David Y. The ets transcription factor Fli-1 in development, cancer and disease  Oncogene. 2015 Apr 16;34(16):2022-2031.

Mohamed Abou El Hassan; Katherine Huang; Manoja B. K. Eswara; Michael Zhao; Lan Song; Tao Yu; Yu Liu; Jeffrey C Liu; Sean McCurdy; Anqi Ma; Joan Wither; Jian Jin; Eldad Zacksenhaus; Jeffrey L Wrana; Rod Bremner. Cancer Cells Hijack PRC2 to Modify Multiple Cytokine Pathways. PloS One, 2015, in press.