Professor and Chair
Ardith and Anna Von Housen
Department of Genetics, Cell Biology and Anatomy
Associate Director of Center for Breast Cancer Research
The Fred and Pamela Buffett Cancer Center
All India Institute of Medical Sciences, India (Ph.D), 1985
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (Post-doc), 1991
Phone: 402-559-8565 (office)
Research - Overall Goals:
The major focus of the laboratory is to delineate molecular mechanisms of early steps in transformation of mammary epithelial cells with the goal of identifying novel molecular diagnostic/prognostic markers and potential therapy targets of breast cancers.
We have identified several new proteins that are involved in mammary epithelial cell transformation. These are: i) E6TP1 (for E6 targeted protein 1) it was later renamed as Sipa1L1 (due to high homology with Sipa1). We are testing the hypothesis that Sipa1L1 functions as a negative regulator of Rap-GTPase in mammary epithelial cell-matrix and cell-cell adhesion; ii) hADA3 (alteration deficiency in activation 3), we have shown that hADA3 is a novel transcriptional co-activator of p53, retinoid receptors and estrogen receptors and thus involved in number of physiological processes; iii) hEcd, the human homologue of drosophila ecdysoneless (Ecd). Cell and knockout mouse model demonstrates that Ecd is involved in cell survival. Current research in the laboratory is to examine the role of these novel targets in epithelial cell growth, differentiation, development, and oncogenesis using both in vitro and in vivo (knock-out) models. Furthermore, an important ongoing area of research is to examine the role of these novel proteins in breast and other carcinomas tumor progression by examining their expression and localization in human tumor tissues.
The other area of interest in the laboratory is to isolate and define stem/progenitor cells that differentiate into different cell types of the mammary gland, such as myoepithelial, luminal or basal cells. We are attempting to develop in vitro and in vivo models of different sub-types of human breast cancers to understand the biological basis of distinct tumor subtypes and exploring these as potential models for therapy.
- Kim JH, Gurumurthy CB, Band H and Band V. Biochemical characterization of human Ecdysoneless reveals a role in transcriptional regulation. Biol. Chem. 2010 Jan; 391(1):9-19.
- Kim JH, Gurumurthy CB, Naramura M. Zhang Y, Dudley AT, Doglio L, Band H, Band V. Role of mammalian Ecdysoneless in cell cycle regulation. J Biol. Chem. 2009 Sept 25; 284 (39):26402-10.
- Zhao X, Lu L, Pokhriyal N. Ma H, Duan L. Lin S, Jafari N, Band H and Band V. Overexpression of RhoA induces preneoplastic transformation of primary mammary epithelial cells. Cancer Res. 2009, Jan 15; 69(2):483-91.
- ZhaoX, GoswamiM, PokhriyalN, MaH, Du H, Yao J, Victor TA, Polyak K, Sturgis CD, Band H and Band V. Cyclooxygenase-2 expression during immortalization and breast cancer progression. Cancer Res., 2008, 68:467-475.
- Germaniuk-kurowska A, Nag A, Zhao X, Dimri, M, Band H and Band V. Ada3 requirement for HAT recruitment to estrogen receptors and estrogen-dependent breast cancer cell proliferation. Cancer Res., 2007 Dec 15, 67(24):11789-97.
- Dimri M, Naramura M, Chen J, Duan I, Fernandes N, Gao Q, Dimri G, Band V*, Band H*. c-Src overexpression imparts ErbB2-like characteristics on EGF receptor in human mammary epithelial cell transformation. Cancer Res. 2007 May 1; 67(9):4164-4172 (*co-corresponding authors).
- ZhaoY, KatzmanRB, DelmolinoL, BhatI, ZhangY, GurumurthyCB, ReddiHV, SolomonA, ZengM, KungA, MaH, GaoQ, DimriG, StanculescuA, MieleL, Wu l, GriffinJD, WazerDE, BandH and BandV. The Notch regulator MAML1 interacts with p53 and functions as a coactivator. J. Biol. Chem. 2007, Apr 20; 282:11969-81.
- Nag A, Germaniuk-Kurowska A, Dimri M, Sassack MA, Gurumurthy CB, Gao Q, Dimri G, Band H and Band V. An essential role of human ADA3 in p53 acetylation. J. Biol. Chem. 2007 Mar 23; 282:8812-20.
- Zhang Y, Chen J, Gurumurthy CB, Kim JH, Bhat I, Gao Q, Dimri G, Lee SW, Band H and Band V. The human orthologue of Drosophila ecdysoneless protein interacts with p53 and regulates its function. Cancer Res. 2006 Jul 15; 66:7167-75.
- Meng G, Zhao Y, Nag A, Zeng M, Dimri G, Gao Q, Wazer DE, Kumar R, Band H, Band V. Human ADA3 binds to estrogen receptor (ER) and functions as a coactivator for ER-mediated transactivation. J. Biol. Chem, 2004 Dec 24;279:54230-40.
- Singh L, Gao Q, Kumar A, Gotoh T, Wazer DE, Band H, Feig LA, Band V. The high-risk human papillomavirus type 16 E6 counters the GAP function of E6TP1 toward small Rap G proteins. J. Virol. 2003 Jan; 77:1614-20.
- Zeng M, Kumar A, Meng G, Gao Q, Dimri G, Wazer D, Band H, Band V. Human papilloma virus 16 E6 oncoprotein inhibits retinoic X receptor-mediated transactivation by targeting human ADA3 coactivator. J. Biol. Chem 2002 Nov 22; 277:45611-18.
- Gao Q, Kumar A, Singh L, Huibregtse JM, Beaudenon S, Srinivasan S, Wazer DE, Band H and Band V. Human papillomavirus E6-induced degradation of E6TP1 is mediated by E6AP ubiquitin ligase. Cancer Res. 2002 June 1; 62:3315-21.
- Kumar A, Zhao Y, Meng G, Zeng M, Srinivasan S, Delmolino LM, Gao Q, Dimri G, Weber, GF, Wazer DE, Band H and Band V. Human papilloma virus oncoprotein E6 inactivates the transcriptional coactivator human ADA3. Mol. Cell. Biol. 2002 Aug; 22:5801-12.
- Dimri GP, Martinez JL, Jacobs JJ, Keblusek P, Itahana K, Van Lohuizen M, Campisi J, Wazer DE, Band V. The Bmi-1 oncogene induces telomerase activity and immoralizes human mammary epithelial cells. Cancer Res. 2002 Aug 15;62:4736-45.
- Dhar S, Bhargava R, Yunes M, Li Biao, Goyal J, Naber S, Wazer DE, Band V. Analysis of noramal epithelial cell specific-1 (NES1)/kallikrein 10 mRNA expression by in situ hybridization, a novel marker for breast cancer. Clin. Cancer Res. 2001 Nov; 7:3393-98.
- Gao Q, Kumar A, Srinivasan S, Singh L, Mukai H, Ono Y, Wazer DE and Band V. PKN binds and phosphorylates human papillomavirus E6 oncoprotein. J. Biol. Chem. 2000 May 19; 275:14824-30.
- Gao Q, Srinivasan S, Boyer SN, Wazer DE, and Band V. The E6 oncoproteins of high-risk papilloma viruses bind to a novel putative GAP protein, E6TP1, and target it for degradation. Mol. Cell. Biol. 1999 Jan 19:733-744.