Concepcion Lab

Research

Mammalian SWI/SNF chromatin remodeling complexes are a heterogeneous group of complexes that have key roles in development and disease. Genes encoding for their subunits are among the most frequent targets of mutation in diverse cancer types – highlighting their central role in human cancer. However, the distinct mechanisms through which specific mutations facilitate malignant transformation and support tumor evolution are still poorly understood. This reflects the complexity of SWI/SNF biology given the heterogeneity of these complexes and the diversity and cell type-specificity of their functions. We seek to understand the functions of these complexes in lung cancer and the mechanisms through which alterations in genes encoding for their subunits contribute to tumorigenesis.

Our research is at the intersection of cancer and chromatin biology. We aim to answer broad questions in the field through the lens of SWI/SNF biology: 1) How do specific SWI/SNF mutations alter the chromatin landscape to facilitate malignant transformation? 2) Which gene regulatory programs are co-opted by SWI/SNF-mutant tumors throughout the course of tumor evolution? 3) What genetic dependencies or targetable features arise in SWI/SNF-mutant lung cancers? Altogether, these will provide broad insights into how altered chromatin states contribute to cell fates as tumors evolve.

Our group uses genetically engineered mouse models (GEMMs), organoids, and patient-derived xenografts (PDXs) as model systems. We leverage cutting-edge technologies in gene editing, chromatin profiling, transcriptomics, and proteomics to determine the functional consequences of SWI/SNF mutations during tumor evolution. We believe that the generation of relevant preclinical models combined with a robust mechanistic understanding of SWI/SNF biology in lung cancer will result in the development of hypothesis-driven therapeutic strategies that can be used to effectively treat patients with lung cancers harboring these mutations.

Beyond our work at the bench, we consciously strive to cultivate a supportive lab environment, provide intentional mentorship for each lab member, and have fun while doing science!

We are actively seeking postdoctoral fellows and graduate students to join our team! Please reach out if you are interested in learning more.

Selected Publications

• Concepcion CP, Ma S, LaFave LM, Bhutkar A, Liu M, DeAngelo LP, Kim JY, Del Priore I, Schoenfeld AJ, Miller M, Kartha VK, Westcott PMK, Sánchez-Rivera FJ, Meli K, Gupta M, Bronson RT, Riely GJ, Rekhtman N, Rudin CM, Kim CF, Regev A, Buenrostro JD, Jacks T. Smarca4 Inactivation Promotes Lineage-Specific Transformation and Early Metastatic Features in the Lung. Cancer Discov. 2022 Feb;12(2):562-585. doi: 10.1158/2159-8290.CD-21-0248. Epub 2021 Sep 24. PubMed PMID: 34561242; PubMed Central PMCID: PMC8831463.
• Gupta M, Concepcion CP, Fahey CG, Keshishian H, Bhutkar A, Brainson CF, Sanchez-Rivera FJ, Pessina P, Kim JY, Simoneau A, Paschini M, Beytagh MC, Stanclift CR, Schenone M, Mani DR, Li C, Oh A, Li F, Hu H, Karatza A, Bronson RT, Shaw AT, Hata AN, Wong KK, Zou L, Carr SA, Jacks T, Kim CF. BRG1 Loss Predisposes Lung Cancers to Replicative Stress and ATR Dependency. Cancer Res. 2020 Sep 15;80(18):3841-3854. doi: 10.1158/0008-5472.CAN-20-1744. Epub 2020 Jul 20. PubMed PMID: 32690724; PubMed Central PMCID: PMC7501156.
• Li X*, Pritykin Y*, Concepcion CP*, Lu Y, La Rocca G, Zhang M, King B, Cook PJ, Au YW, Popow O, Paulo JA, Otis HG, Mastroleo C, Ogrodowski P, Schreiner R, Haigis KM, Betel D, Leslie CS, Ventura A. High-Resolution In Vivo Identification of miRNA Targets by Halo-Enhanced Ago2 Pull-Down. Mol Cell. 2020 Jul 2;79(1):167-179.e11. doi: 10.1016/j.molcel.2020.05.009. Epub 2020 Jun 3. PubMed PMID: 32497496; PubMed Central PMCID: PMC7446397. *equal contribution
• Maddalo D, Manchado E, Concepcion CP, Bonetti C, Vidigal JA, Han YC, Ogrodowski P, Crippa A, Rekhtman N, de Stanchina E, Lowe SW, Ventura A. In vivo engineering of oncogenic chromosomal rearrangements with the CRISPR/Cas9 system. Nature. 2014 Dec 18;516(7531):423-7. doi: 10.1038/nature13902. Epub 2014 Oct 22. PubMed PMID: 25337876; PubMed Central PMCID: PMC4270925.
• Concepcion CP, Han YC, Mu P, Bonetti C, Yao E, D'Andrea A, Vidigal JA, Maughan WP, Ogrodowski P, Ventura A. Intact p53-dependent responses in miR-34-deficient mice. PLoS Genet. 2012;8(7):e1002797. doi: 10.1371/journal.pgen.1002797. Epub 2012 Jul 26. PubMed PMID: 22844244; PubMed Central PMCID: PMC3406012.