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Dr. Testa’s laboratory investigates the role of genetic alterations in human malignant mesothelioma, a cancer of the cells that line the chest and abdominal cavities, primarily caused by exposure to asbestos. His group discovered frequent mutations of the CDKN2A/ARF locus, a region of DNA that encodes the tumor suppressing genes p16INK4a and p14ARF, and NF2 in human mesothelioma. The laboratory's current work on mesothelioma focuses on investigating the various molecular signaling pathways that are hyper-activated in this disease in order to identify potential new, druggable targets for cancer therapy or prevention.

The Testa laboratory also developed the first mouse model that faithfully reproduces many of the molecular features of human mesothelioma, which allows them to better understand mesothelioma tumor formation and even test new therapies that could later be used in humans. This mouse model is particularly useful since it demonstrates many characteristics common to the human form of the disease, including frequent inactivation of the NF2 and CDKN2A/ARF tumor suppressor genes, and hyper-activation of the enzyme AKT, which plays a central role in the creation of tumors.

1. Altomare DA, Menges CW, Pei J, Zhang L, Skele-Stump KL, Carbone M, Kane AB, Testa JR. Activated TNFα/NFκB signaling via down regulation of Fas-associated factor 1 in asbestos-induced mesotheliomas from Arf knockout mice. Proc Natl Acad Sci USA. 2009;106:3420-5. PubMed
2. Tan Y, Timakhov RA, Rao M, Altomare DA, Xu J, Liu Z, Gao Q, Jhanwar SC, Di Cristofano A, Wiest DL, Knepper JE, Testa JR. A novel recurrent chromosomal inversion implicates the homeobox gene Dlx5 in T-Cell lymphomas from Lck-Akt2 transgenic mice. Cancer Res. 2008;68:1296-1302. PubMed
3. Mabuchi S, Altomare DA, Connolly DC, Klein-Szanto A, Litwin S, Hoelzle MK, Hensley HH, Hamilton TC, Testa JR. RAD001 (Everolimus) delays tumor onset and progression in a transgenic mouse model of ovarian cancer. Cancer Res (Priority Report). 2007;67:2408-13. PubMed
4. Altomare DA, Vaslet CA, Skele KL, De Rienzo A, Devarajan K, Jhanwar SC, McClatchey AI, Kane AB, Testa JR. A mouse model recapitulating molecular features of human mesothelioma. Cancer Res (Priority Report). 2005 65:8090-5. PubMed
5. Xiao GH, Gallagher R, Shetler J, Skele K, Altomare DA, Pestell RG, Jhanwar S, Testa JR. The NF2 tumor suppressor gene product, merlin, inhibits cell proliferation and cell cycle progression by repressing cyclin D1 expression. Mol Cell Biol. 2005;25:2384-94. PubMed
6. Altomare DA, You H, Xiao GH, Ramos-Nino ME, Skele KL, De Rienzo A, Jhanwar SC, Mossman BT, Kane AB, Testa JR. Human and mouse mesotheliomas exhibit elevated AKT/PKB activity, which can be targeted pharmacologically to inhibit tumor cell growth. Oncogene. 2005;24:6080-9. PubMed
7. Bellacosa A, Kumar CC, Di Cristofano A, Testa JR. Activation of AKT kinases in cancer: implications for therapeutic targeting. Adv Cancer Res. 2005;94:29-86. PubMed