Selected Publications

Context dependent effects of amplified MAPK signaling during lung adenocarcinoma initiation and progression.
Cicchini M, Buza EL, Sagal KM, Gudiel AA, Durham AC, and
Feldser DM (2017). Cell Reports 2017 In Press.
Amplification of MAPK signaling drives tumor progression, but also induces tumor formation in CC10+ cells that are recalcitrant KrasG12-mediated transformation. Subsequent to initiation, CC10+ cells transdifferentiate toward an alveolar type II (SPC+) phenotype. Immunostaining of lung sections from KrasLSL-G12D/+;p53flox/flox; Rosa26LSL-YFP/+ mice infected with CC10-restricted Adeno-Cre. Braf inhibition (PLX4720) expands SPC+ adenomas (upper left of image) and induces transformation of CC10+ proximal airway cells (middle and inset). DAPI (white), YFP (yellow), CC10, (cyan), and SPC (red).
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Systematic in vivo inactivation of chromatin regulating enzymes identifies Setd2 as a potent tumor suppressor in lung adenocarcinoma.
Walter DM, Venancio OS, Buza EL, Tobias JW, Deshpande C, Gudiel AA, Kim-Kiselak C, Cicchini M, Yates TJ, and
Feldser DM (2017). Cancer Research. 2017 In Press.
LentiCRISPRv2Cre was constructed to facilitate rapid assessment of tumor suppressor gene potential in established, cre-based, genetically engineered mouse models of cancer. Using this approach we identified that Setd2, the H3K36me3 transferase, is a potent tumor suppressor gene in KrasLSL-G12D/+ and KrasLSL-G12D/+;p53flox/flox models of lung adeno(carcinoma).
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XTR: A recombinase-based system for regulating gene function in a conditional and reversible manner.
Robles-Oteiza C, Taylor SE, Yates T, Cicchini M, Lauderback B, Cashman C, Burds AA, Winslow M, Jacks T, and
Feldser DM (2015) Nat Commun. 2015 Nov 5;6:8783. PMID: 26537451 PMCID: 4635517
XTR alleles facilitate Cre-mediated inactivation and subsequent Flp-dependent restoration of endogenous genes. Cre drives irreversible inversion of a double-floxed gene trap consisting of a splice acceptor (SA), enhanced green fluorescent protein (GFP) cDNA, and the polyadenylation transcriptional terminator sequence (pA). Stable inversion accepts splicing from upstream exons in the host gene, reads out GFP expression, and then terminates transcription leading to functional inactivation of the host gene’s expression. Flp drives deletion of the gene trap (SA-GFP-pA) thereby restoring normal splicing of the host gene.
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Xue W, Li Y, Park A, Moue H, Cansu C, Bizhanova A, Akama-Garren E, Joshi J, Hendrickson E, Feldser DM, Yin, Anderson DG, Jacks T, Weng, Z (2015) A versatile reporter system for CRISPR-mediated chromosomal rearrangements. Genome Biology, May 28;16:111.. PubMed PMID: 26018130; PubMed Central PMCID: PMC4465146

Chiou SH, Kim-Kiselak C, Risca V, Heimann M, Chuang CH, Burds A, Greenleaf W, Jacks T,
Feldser DM, Winslow MM (2014). A conditional system to specifically link disruption of protein-coding function with reporter expression in mice. Cell Reports 7(6): 2078-86. PMID: 24931605; PMCID: PMC4113058. PDF

Xue W, Meylan E, Oliver TG,
Feldser DM, Winslow MM, Bronson R, Jacks T. Response and resistance to NF-κB inhibitors in mouse models of lung adenocarcinoma. Cancer Discovery. 2011. 1(3):236-47. PMID:21874163, PMCID:PMC3160630. PDF

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. 473(7345):101-4. PMID:21471965, PMCID:PMC3088778. PDF

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. 468(7323):572-5. PMID:21107428, PMCID:PMC3003305. PDF

Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, Khalil AM, Zuk O, Amit I, Rabani M, Attardi LD, Regev A, Lander ES, Jacks T, Rinn JL. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 2010. 142(3):409-19. PMID:20673990, PMCID:PMC2956184. PDF

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. 462(7269):104-7. PMID:19847165, PMCID:PMC2780341. PDF

Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, Cabili MN, Jaenisch R, Mikkelsen TS, Jacks T, Hacohen N, Bernstein BE, Kellis M, Regev A, Rinn JL, Lander ES. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009. 458(7235):223-7. PMID:19182780, PMCID:PMC2754849. PDF

Godar S, Ince TA, Bell GW, Feldser D, Donaher JL, Bergh J, Liu A, Miu K, Watnick RS, Reinhardt F, McAllister SS, Jacks T, Weinberg RA. Growth-inhibitory and tumor- suppressive functions of p53 depend on its repression of CD44 expression. Cell. 2008. 134(1):62-73. PMID:18614011, PMCID:PMC3222460. PDF

Feldser DM, Greider CW. Short telomeres limit tumor progression in vivo by inducing senescence. Cancer Cell. 2007. 11(5):461-9. PMID:17433785, PMCID:PMC1945093. PDF

Feldser D, Strong MA, Greider CW. Ataxia telangiectasia mutated (Atm) is not required for telomerase-mediated elongation of short telomeres. Proceedings of the National Academy of Sciences USA. 2006. 103(7):2249-51. PMID:16467146, PMCID:PMC1413760. PDF

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. 123(6):1121-31. PMID:16360040. PDF

Feldser DM, Hackett JA, Greider CW. Telomere dysfunction and the initiation of genome instability. Nature Reviews Cancer. 2003. 3(8):623-7. PMID:12894250. PDF

Feldser DM, Kern SE. Oncogenic levels of mitogen-activated protein kinase (MAPK) signaling of the dinucleotide KRAS2 mutations G12F and GG12-13VC. Human Mutation. 2001. 18(4):357. PMID:11668624. PDF

Hackett JA, Feldser DM, Greider CW. Telomere dysfunction increases mutation rate and genomic instability. Cell. 2001. 106(3):275-86. PMID:11509177. PDF

Feldser D, Agani F, Iyer NV, Pak B, Ferreira G, Semenza GL. Reciprocal positive regulation of hypoxia-inducible factor 1alpha and insulin-like growth factor 2. Cancer Research. 1999. 59(16):3915-8. PMID:10463582. PDF
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