Dr. Madhuri Wadehra's research and discovery efforts are focused on two related themes in tumor biology: understanding the function of a tetraspan protein epithelial membrane protein-2 (EMP2) in tumor progression, and developing therapeutic and diagnostic agents that target tumors that overexpress EMP2.
Wadehra's team is currently investigating a promising marker in a number of cancers, the tetraspan protein EMP2. They have shown that EMP2 functions as an oncogene in many of these human cancers and that it is dysregulated in a number of tumors including those of the female reproductive system as well as primary CNS tumors. Wadehra's lab is focused on:
- Defining the biochemical function of EMP2
- Characterizing the role of EMP2 and other family members (i.e., PMP22) in cell-cell and cell-extracellular matrix interactions
- Defining the role of EMP2 in malignant progression
- Determining, using Tissue Microarray technology, whether EMP2 is a diagnostic and/or prognostic indicator for tumor development and progression
In addition, Wadehra is interested in translating the effects of EMP2 to the clinic and developing it as a therapeutic and/or diagnostic target. They have developed recombinant antibodies (diabody, minibody, native IgG1) specific for EMP2 with the purpose of using these agents for image guided therapy. These different antibody-sized antibody fragments allow for tailoring of the immune response and control of the reagent half-life. Her lab has successfully used anti-EMP2 minibodies for microPET imaging of EMP2 positive tumors. Moreover, recombinant EMP2 diabodies and the full length IgG1 illicit strong intrinsic anti-proliferative/pro-apoptotic activity against endometrial, ovarian, breast and glioblastoma cell lines. Her team is currently working to understand the mechanism of these reagents in tumor cells in order to develop their potential use in the clinic.
Fu M, Rao R, Sudhakar D, Hogue CP, Rutta Z, Morales S, Gordon LK, Braun J, Goodglick L, Wadehra M. Epithelial membrane protein-2 promotes endometrial tumor formation through activation of FAK and Src. PLoS One. 2011;6(5):e19945. Epub 2011 May 27.
Morales SA, Telander D, Notterpek L, Wadehra M, Braun J, Gordon LK. Rewiring integrin-mediated signaling and cellular response with the peripheral myelin protein 22 and epithelial membrane protein 2 components of the tetraspan web. Invest Ophthalmol Vis Sci. 2011 Jul 23;52(8):5465-72. Print 2011 Jul.
Habeeb O, Goodglick L, Soslow RA, Rao RG, Gordon LK, Schirripa O, Horvath S, Braun J, Seligson DB, Wadehra M. Epithelial membrane protein-2 expression is an early predictor of endometrial cancer development. Cancer. 2010 Oct 15;116(20):4718-26.
Fu M, Maresh EL, Soslow RA, Alavi M, Mah V, Zhou Q, Iasonos A, Goodglick L, Gordon LK, Braun J, Wadehra M. Epithelial membrane protein-2 is a novel therapeutic target in ovarian cancer. Clin Cancer Res. 2010 Aug 1;16(15):3954-63.
Shimazaki K, Lepin EJ, Wei B, Nagy AK, Coulam CP, Mareninov S, Fu M, Wu AM, Marks JD, Braun J, Gordon LK, Wadehra M. Diabodies targeting epithelial membrane protein 2 reduce tumorigenicity of human endometrial cancer cell lines. Clin Cancer Res. 2008 Nov 15;14(22):7367-77.