Professor & Chair
Department of Genetics, Cell Biology and Anatomy
PhD, All India Institute of Medical Sciences, India, 1985
Post-doc, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 1994
Ardith and Anna Von Housen Chair, Genetics, Cell Biology and Anatomy
Associate Director, Center for Breast Cancer Research, Fred and Pamela Buffett Cancer Center
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.
- Mohapatra BC, Mirza, Bele A, Gurumurthy CB, Raza M, Saleem I, Storck MD, Sarkar A, Kolala SS, Shukla SK, Southekal S, Wagner KU, Qiu F, Lele SM, Alsaleem MA, Rakha EA, Guda C, Singh PK, Cardiff RD, Band H and Band V. ECD overexpression drives mammary tumorigenesis through upregulation of c-MYC and glucose metabolism. Mol Cancer Res. 2022. Sep 2;20(9):1391-1404.
- Mirza S, Kalluchi A, Raza M, Saleem I, Pal D, Mohapatra B, Sarkar A, Lele S, Quellette M, Qiu F, Yu L, Lobanov A, Zheng Z-M, Zhang Y, Alsaleem MA, Rakha EA, Band H, Rowley MJ and Band V. Ecdysoneless protein regulates viral and cellular mRNA splicing to promote cervical oncogenesis. Mol Cancer Res. 2022 Feb;20(2):305-318.
- Saleem I, Mirza S, Sarkar A, Raza M, Mohapatra B, Mushtaq I, Kim JH, Mishra NK, Alsaleem MA, Rakha EA, Qiu F, Guda C, Band H and Band V. The mammalian ecdysoneless protein interacts with RNA helicase DDX39A to regulate nuclear mRNA export. Mol. Cell. Biol. 2021 Jun 23;41(7):e0010321.
- Olou AA, Sarkar A, Bele A, Gurumurthy CB, Mir RA, Ammons SA, Mirza S, Saleem I, Urano F, Band H, Band V. Mammalian ECD protein is a novel negative regulator of the PERK arm of unfolded protein response. Mol. Cell. Biol. 2017 Aug 28;37(18).
- Srivastava S, Mohibi S, Mirza S, Band H and Band V. Epidermal Growth Factor Induces ADA3 Acetylation through AKT-p300 Pathway. Cell Cycle, 2017 Aug 18;16(16):1515-1525.
- Bhagirath D, Zhao X, Mirza S, West WW, Band H, Band V. Mutant PIK3CA Induces EMT in a Cell Type Specific Manner. PLoS One. 2016 Dec 12;11(12):e0167064.
- Griffin NI, Sharma G, Zhao X, Mirza S, Srivastava S, Dave BJ, Aleskandarany M, Rakha E, Mohibi S, Band H, Band V. ADA3 regulates normal and tumor mammary epithelial cell proliferation through c-MYC. Breast Cancer Res. 2016 Nov 16;18(1):113.
- Mohibi S, Srivastava S, Bele A, Mirza S, Band H, Band V. Acetylation of Mammalian ADA3 Is Required for Its Functional Roles in Histone Acetylation and Cell Proliferation. Mol Cell Biol. 2016 Sep 12;36(19):2487-502.
- Mir RA, Bele A, Mirza S, Srivastava S, Olou AA, Ammons SA, Kim JH, Gurumurthy CB, Qiu F, Band H, Band V.A Novel Interaction of Ecdysoneless (ECD) Protein with R2TP Complex Component RUVBL1 Is Required for the Functional Role of ECD in Cell Cycle Progression.Mol Cell Biol. 2015 Dec 28;36(6):886-99.
- Mohibi S, Srivastava S, Wang-France J, Mirza S, Zhao X, Band H, Band V. Alteration/Deficiency in Activation 3 (ADA3) Protein, a Cell Cycle Regulator, Associates with the Centromere through CENP-B and Regulates Chromosome Segregation. J Biol Chem. 2015 Nov 20;290(47):28299-310.
- Bele A, Mirza S, Zhang Y, Mir R, Lin S, Kim JH, Gurumurthy CB, West W, Qiu F, Band H, Band V. The cell cycle regulator Ecdysoneless cooperates with H-Ras to promote oncogenic transformation of human mammary epithelial cells. Cell Cycle. 2015;14(7):990-1000.
- Malhotra GK, Zhao X, Edwards E, Kopp JL, Naramura M, Sander M, Band H, Band V. The role of Sox9 in mouse mammary gland development and maintenance of mammary stem and luminal progenitor cells. BMC Dev Biol. 2014 Dec 20;14(1):47.
- Mirza S, Rakha EA, Alshareeda A, Mohibi S, Zhao X, Katafiasz BJ, Wang J, Gurumurthy CB, Bele A, Ellis IO, Green AR, Band H, Band V. Cytoplasmic localization of alteration/deficiency in activation 3 (ADA3) predicts poor clinical outcome in breast cancer patients. Breast Cancer Res Treat. 2013 Feb; 137(3):721-31.
- Mohibi S, Gurumurthy CB, Nag A, Wang J, Mirza S, Mian Y, Quinn M, Katafiasz B, Eudy J, Pandey S, Guda C, Naramura M, Band H, Band V. Mammalian alteration/deficiency in activation 3 (Ada3) is essential for embryonic development and cell cycle progression. J Biol Chem. 2012 Jun 26; 287(35):29442-56.
- Zhao X, Mirza S, Alshareeda A, Zhang Y, Gurumurthy CB, Bele A, Kim JH, Mohibi S, Goswami M, Lele SM, West W, Qiu F, Ellis IO, Rakha EA, Green AR, Band H, Band V. Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients. Breast Cancer Res Treat. 2012 Jul; 134(1):171-80.