Our research is dedicated to deconstructing the multistep process of tumorigenesis. The major emphasis of our laboratory is to uncover the pathways that are disabled by mutational inactivation of tumor-suppressor genes as well as those pathways stimulated by aberrant oncogene activation. Areas of interest within the laboratory include: p53-regulated tumor immune surveillance, Rb-mediated tumor suppression, chemical genetic strategies to modulate tumor suppression, development of gene regulating tools for mouse models, and Kras signaling in lung cancer.
The Feldser Laboratory
The Feldser lab uses genetically engineered mouse models to study tumor progression and metastasis of common forms of human cancer. These models faithfully recapitulate many aspects of the histopathological progression of their human counterparts. Tumors initiate within the appropriate tissue microenvironment from single cells due to induced activation of latent oncogenes and/or deletion of key tumor suppressor genes. These lesions evolve through multiple cellular states toward malignant and metastatic disease. We focus on mouse models in order to employ novel genetic tools to regulate gene function at will in developing cancerous lesions as well as track cancer growth and dissemination via bioluminescent and fluorescent techniques. We couple cellular, genomic and biochemical analyses to our powerful in vivo tools to discern the mechanics of tumor progression and metastasis with the goal of identifying new therapeutic strategies to eradicate malignant cells.
01. Xue W, Meylan E, Oliver TG, Feldser DM, Winslow MM, Bronson R, Jacks T. Response and resistance to NF-?B inhibitors in mouse models of lung adenocarcinoma. Cancer Discov. 2011 Aug;1(3):236-47.
02. Winslow MM, Dayton TL, Verhaak RG, Kim-Kiselak C, Snyder EL, Feldser DM, Hubbard DD, DuPage MJ, Whittaker CA, Hoersch S, Yoon S, Crowley D, Bronson RT, Chiang DY, Meyerson M, Jacks T. Suppression of lung adenocarcinoma progression by Nkx2-1. Nature. 2011 May 5;473(7345):101-4.
03. Feldser DM, Kostova KK, Winslow MM, Taylor SE, Cashman C, Whittaker CA, Sanchez-Rivera FJ, Resnick R, Bronson R, Hemann MT, Jacks T. Stage-specific sensitivity to p53 restoration during lung cancer progression. Nature. 2010 Nov 25;468(7323):572-5.
04. Meylan E, Dooley AL, Feldser DM, Shen L, Turk E, Ouyang C, Jacks T. Requirement for NF-kappaB signalling in a mouse model of lung adenocarcinoma. Nature. 2009 Nov 5;462(7269):104-7.
05. Feldser DM, Greider CW. Short telomeres limit tumor progression in vivo by inducing senescence. Cancer Cell. 2007 May;11(5):461-9.
06. Hao LY, Armanios M, Strong MA, Karim B, Feldser DM, Huso D, Greider CW. Short telomeres, even in the presence of telomerase, limit tissue renewal capacity. Cell. 2005 Dec 16;123(6):1121-31.
07. Feldser DM, Hackett JA, Greider CW. Telomere dysfunction and the initiation of genome instability. Nat Rev Cancer. 2003 Aug;3(8):623-7.
08. Feldser DM, Kern SE. Oncogenic levels of mitogen-activated protein kinase (MAPK) signaling of the dinucleotide KRAS2 mutations G12F and GG12-13VC. Hum Mutat. 2001 Oct;18(4):357.
09. Hackett JA, Feldser DM, Greider CW. Telomere dysfunction increases mutation rate and genomic instability. Cell. 2001 Aug 10;106(3):275-86.
Brian Donahower - Research Specialist
Caroline Kitzmiller - Administrative Coordinator
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