- Assistant Professor, Microbiology, Immunology, and Cancer Biology
Mechanisms of tumor progression and homeostasis
Functional validation of SCLC genomic alterations: Our goal is to define oncogenic drivers of SCLC using streamlined and informed ways of characterizing genomic alterations in tumor progression. We have established a tractable model in which candidate mutations are characterized in pre-cancerous cells using virus-mediated gene manipulation including CRIPSR-mediated mutation.
Transcriptional regulation during tumor progression: A majority of solid tumors have somatic alterations in transcription factors and chromatin modifiers, which cause aberrant expression of a broad range of genes related to cell proliferation and death. We characterize the deregulated transcription programs to identify potential therapeutic targets.
Signaling pathways in tumor progression and homeostasis: Developmental and growth factor signaling pathways, including Hh and Wnt, are deregulated in cancer cells; Modulation of the signaling pathways would be a viable therapeutic strategy. Using mouse models and biochemical approaches we characterize the pathways in the context of tumor development and chemo-response.
Metabolic plasticity during tumor progression: Altered metabolism plays important roles in tumorigenesis; however, oncogenic alterations in metabolism may vary among tissue types and be specific to oncogenic driver. Defining metabolic plasticity unique to tumor progression would provide important opportunities to design preventive strategies involving nutrition or drugs with low-toxicity.
- Jahchan N, Dudley J, Mazur P, Flores N, Yang D, Palmerton A, Zmoos A, Vaka D, Tran K, Zhou M, Krasinska K, Riess J, Neal J, Khatri P, Park K, Butte A, Sage J. A drug repositioning approach identifies tricyclic antidepressants as inhibitors of small cell lung cancer and other neuroendocrine tumors. Cancer discovery. 2013;3(12): 1364-77. PMID: 24078773 | PMCID: PMC3864571
- Peifer M, Fernández-Cuesta L, Sos M, George J, Seidel D, Kasper L, Plenker D, Leenders F, Sun R, Zander T, Menon R, Koker M, Dahmen I, Müller C, Di Cerbo V, Schildhaus H, Altmüller J, Baessmann I, Becker C, de Wilde B, Vandesompele J, Böhm D, Ansén S, Gabler F, Wilkening I, Heynck S, Heuckmann J, Lu X, Carter S, Cibulskis K, Banerji S, Getz G, Park K, Rauh D, Grütter C, Fischer M, Pasqualucci L, Wright G, Wainer Z, Russell P, Petersen I, Chen Y, Stoelben E, Ludwig C, Schnabel P, Hoffmann H, Muley T, Brockmann M, Engel-Riedel W, Muscarella L, Fazio V, Groen H, Timens W, Sietsma H, Thunnissen E, Smit E, Heideman D, Snijders P, Cappuzzo F, Ligorio C, Damiani S, Field J, Solberg S, Brustugun O, Lund-Iversen M, Sänger J, Clement J, Soltermann A, Moch H, Weder W, Solomon B, Soria J, Validire P, Besse B, Brambilla E, Brambilla C, Lantuejoul S, Lorimier P, Schneider P, Hallek M, Pao W, Meyerson M, Sage J, Shendure J, Schneider R, Büttner R, Wolf J, Nürnberg P, Perner S, Heukamp L, Brindle P, Haas S, Thomas R. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nature genetics. 2012;44(10): 1104-10. PMID: 22941188
- Park K, Liang M, Raiser D, Zamponi R, Roach R, Curtis S, Walton Z, Schaffer B, Roake C, Zmoos A, Kriegel C, Wong K, Sage J, Kim C. Characterization of the cell of origin for small cell lung cancer. Cell cycle (Georgetown, Tex.). 2011;10(16): 2806-15. PMID: 21822053 | PMCID: PMC3219544
- Park K, Martelotto L, Peifer M, Sos M, Karnezis A, Mahjoub M, Bernard K, Conklin J, Szczepny A, Yuan J, Guo R, Ospina B, Falzon J, Bennett S, Brown T, Markovic A, Devereux W, Ocasio C, Chen J, Stearns T, Thomas R, Dorsch M, Buonamici S, Watkins D, Peacock C, Sage J. A crucial requirement for Hedgehog signaling in small cell lung cancer. Nature medicine. 2011;17(11): 1504-8. PMID: 21983857 | PMCID: PMC3380617
- Schaffer B, Park K, Yiu G, Conklin J, Lin C, Burkhart D, Karnezis A, Sweet-Cordero E, Sage J. Loss of p130 accelerates tumor development in a mouse model for human small-cell lung carcinoma. Cancer research. 2010;70(10): 3877-83. PMID: 20406986 | PMCID: PMC2873158