top of page
publication image


Selected Publications

Cell paper lineage tracing thumbnail

Yang D*, Jones MG*, Naranjo S, Rideout W, Min KH, Ho R, Wu W, Qiu X, Replogle JM, Page J, Quinn JJ, Horns F, Chen MZ, Freed-Pastor W, McGinnis CS, Patterson DM, Gartner ZJ, Chow E, Bivona TG, Chan MM, Yosef N, Jacks T and Weissman JS. (2022) Lineage tracing reveals the phylodynamics, plasticity and paths of tumor evolution. Cell, Volume 185(11):1905-1923. *Equal Contribution

Summary:  We engineered an evolving CRISPR-based, single cell lineage tracer into a mouse model of Kras;Trp53(KP)-driven lung adenocarcinoma. This KP-Tracer system can monitor the process by which a tumor evolves in vivo from a single transformed cell to aggressive and metastatic states. It enables us to track the evolutionary history of many independently-initiated tumors and discern the recurring patterns of tumor clonal dynamics, cellular plasticity, and metastatic routes with unprecedented resolution.

Highlight: This work was highlighted by Nature Research Highlight, and Wong, WH and Curtis C, Dev Cell, 2022, and was chosen as the finalist (top3) by 2022 STAT madness science competition.

Cell paper Nfib thumbnail

Denny SK*, Yang D*, Chuang CH, Brady JJ, Lim JS, Grüner BM, Chiou SH, Schep AN, Baral J, Hamard C, Antoine M, Wislez M, Kong CS, Connolly AJ, Park KS, Sage J, Greenleaf WJ, Winslow MM. (2016) Nfib promotes metastasis through a widespread increase in chromatin accessibility. Cell, Volume 166(2), 328-42. *Equal Contribution

Summary: Genomic amplification and high expression of a single transcription factor Nfib is sufficient to profoundly reprogram the epigenomic landscape of SCLC cells and to drive their ability to metastasize, providing a new paradigm to explain cancer progression.

Highlight: This work was highlighted by Minna et al. Cell, 2016, and Gazdar et al. Nature Reviews Cancer, 2017, and by Rudin et al. Nature Reviews Clinical Oncology, 2017 as one of the three major discoveries of small cell lung cancer in 2016.

Cancer discovery paper thumbnail

Yang D, Denny SK, Greenside PG, Chaikovsky A, Brady JJ, Ouadah Y, Granja JM, Jahchan NS, Lim JS, Kowk S, Kong CS, Berghoff AS, Schmitt A, Reinhardt HC, Park KS, Preusser M, Kundaje A, Greenleaf WJ, Sage J and Winslow MM. (2018) Intertumoral heterogeneity is influenced by the cell type of origin. Cancer Discovery, Volume 8(10): 1316-1331.

Summary: We discovered that the cell of origin is a crucial determinant of which mechanisms of metastatic progression the cancer employs. We have identified that two different subtypes of SCLC exist and that the cell of origin has a profound impact on the ultimate mechanisms of tumor metastasis.

Highlight: This work was highlighted by Seton-Rogers et al. Nature Reviews Cancer, 2018, and Pozo et al. Cancer Discovery, 2018 as one of the first examples demonstrating the cellular contexts of tumor initiating cells have profound impact on tumor progression and metastasis.

Elife paper thumbnail

Yang D, Qu F, Cai H, Chuang CH, Lim JS, Jahchan N, Grüner BM, S Kuo C, Kong C, Oudin MJ, Winslow MM, Sage J. (2019) Axon-like protrusions promote small cell lung cancer migration and metastasis. Elife, pii: e50616.

Summary: We uncovered that small cell lung cancer cells can undergo a partial neuroendocrine-to-neuronal trans-differentiation and generate axon-like protrusions. Cancer cells can co-opt neuronal migration programs to facilitate migration and extravasation.

Highlight: This work was highlighted by Jung et al, Int J Cancer, 2020, and Desai, Annu Rev of Cancer Biology, 2021.

Annual review of Cancer biology paper thumbnail

Jones MG*, Yang D* ^, Weissman JS^. (2022) New tools for lineage tracing in cancer in vivo. Annual Review of Cancer Biology,  in press. *Equal Contribution, ^ Co-corresponding author

Genes and Development paper thumbnail

Naranjo S, Cabana CM, LaFave LM, Westcott PMK, Romero R, Ghosh A, Liao LZ, Schenkel JM, Priore, ID, Bhutkar A, Yang D, Jacks T. (2022) Modeling diverse genetic subtypes of lung adenocarcinoma with a next-generation alveolar type 2 organoid platform. Genes and Development, in press. Biorxiv.

Qu F, Cao S, Michno W, Madubata CJ, Puno A, Drainas AP, Lee MC, Yang D, …, Paşca AM, Sage J. (2022) Neuronal mimicry generates an ecosystem critical for brain metastatic growth of SCLC. Biorxiv.

Cell paper single cell thumbnail

Qiu X*, Zhang Y*, Martin-Rufino J, Weng C, Hosseinzadeh S, Yang D, Pogson A, Wang L, Shurtleff M, Yuan R, Xu S, Ma Y, Replogle JM, Darmanis S, Bahar I, Xing J, Weissman JS. (2022) Mapping transcriptomic vector fields of single cells. Cell, Volume 185(4):690-711 *Equal Contribution

Cell paper DNA repair thumbnail

Hussmann JA, Ling J, Ravisankar P, Yan J, Cirincione A, Xu A, Simpson D, Yang D, …, Adamson B. (2021) Mapping the genetic landscape of DNA double-strand break repair. Cell, Volume 184(22):5653-5669.

Koblan LW, Hussmann JA, Shen M, Arbab M, Sisley, T, Yang D, Replogle JM, Mok B, Adamson B, Weissman JS, Liu DR (2021). Development of a set of C•G-to-G•C transversion base editors from CRISPRi screens, target-library analysis, and machine learning. Nature Biotechnology, Volume 39(11):1414-1425.

Cancer research paper lung cancer thumbnail

Chuang CH, Dorsch M, Dujardin P, Silas S, Ueffing K, Hölken JM, Yang D, Winslow MM, Grüner, BM. (2021). Altered mitochondria functionality defines a metastatic cell state in lung cancer and creates an exploitable vulnerability. Cancer Research, Volume 81(3):567-579.

Nature article 1 thumbnail

Chan M, Smith ZD, Grosswendt S, Kretzmer H, Norman TM, Adamson B, Jost M, Quinn JJ, Yang D, Jones MG, Khodaverdian A, Yosef N, Meissner A, Weissman JS. (2019) Molecular recording of mammalian embryogenesis. Nature, Volume 570(7759):77-82

Lim JS, Ibaseta A, Fischer MM, Cancilla B, O’Young G, Cristea S, Luca V, Yang D, Jahchan N, Hamard C, Antoine M, Wislez M, …, Murriel CL and Sage J. (2017) Notch signaling defines a novel level of intratumoral heterogeneity that contributes to tumorigenesis in small cell lung cancer. Nature, Volume 545(7654): 360-364.

Cancer discoery paper 2 thumbnail

Chiou SH, Risca VI, Wang GX, Yang D, Grüner BM, Kathiria AS, Ma RK, Vaka D, Chu P, Kozak M,Castellini L, Graves EE, Kim GE, Mourrain P, Koong AC, Giaccia AJ, Winslow MM. (2017) Blimp1 induced transient metastatic heterogeneity in pancreatic cancer. Cancer Discovery, Volume 7(10): 1184-99.

Nature medicine article thumbnail

Chuang CH, Greenside PG, Rogers ZN, Brady JJ, Yang D, Caswell DR, Ma RK, Winters A, Kopecky KE, Chiou SH, Grüner BM, Ramaswami G, Sweet-Cordero EA, Li JB, Kundaje A, and Winslow MM. (2017) Molecular definition of a metastatic lung cancer state reveals a targetable CD109/Jak/Stat axis. Nature Medicine, Volume 23(3): 291-300.

Nature methods thumbnail

Grüner BM*, Schulze CJ*, Yang D, Ogasawara D, Dix M, Chuang CH, Rogers ZN, Brown JM, Cravatt B, Bogyo M, Winslow MM. (2016) An in vivo multiplexed small-molecule screening platform. Nature Methods, Volume 13(10): 883-9. *Equal Contribution.

Weiskopf K, Jahchan NS, Schnorr PJ, Cristea S, Ring AM, Maute RL, Volkmer AK, Volkmer JP, Liu J, Lim JS, Yang D, …, Weissman IL, Sage J. (2016) Cd47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer.  Journal of Clinical Investigation, Volume 126(7), 2610-20.

Nature article 2 thumbnail

George J, Lim JS, Jang SJ, Cun Y, Ozretić L, Kong G, Leenders F, Lu X, Fernández-Cuesta L, Bosco G, Müller C, Dahmen I, Jahchan NS, Park KS, Yang D, …, Haas SA, Brambilla E, Peifer M, Sage J, Thomas RK. (2015) Comprehensive genomic profiles of small cell lung cancer. Nature, Volume 524(7563), 47-53.

Jahchan NS, Lim JS, Bola B, Morris K, Seitz G, Tran KQ, Xu L, Trapani F, Morrow CJ, Cristea S, Coles GL, Yang D, …, Peifer M, Dive C, Sage J. (2016) Identification and targeting of long-term tumor-propagating cells in small cell lung cancer. Cell Reports, Volume 16(3), 644-56.

Pancreatic cancer paper thumbnail

Caswell DR*, Chuang CH*, Yang D, Chiou SH, Cheemalavagu S, Kim-Kiselak C, Connolly A, Winslow MM. (2014) Obligate progression precedes lung adenocarcinoma dissemination. Cancer Discovery, Volume 4(7), 781-9. *Equal Contribution.

Chiou SH, Winters IP, Wang J, Naranjo S, Dudgeon C, Tamburini FB, Brady JJ, Yang D, Grüner BM, …, Kim SK, Winslow MM. (2015) Pancreatic cancer modeling using retrograde viral vector delivery and in vivo CRISPR/Cas9-mediated somatic genome editing. Genes and Development, Volume 29(14), 1576-1585.

Drug repositioning article thumbnail

Jahchan NS, Dudley JT, Mazur PK, Flores N, Yang D, Palmerton A, Zmoos AF, Vaka D, Tran KQ, Zhou M, Krasinska K, Riess JW, Neal JW, Khatri P, Park KS, Butte AJ, Sage J. (2013) A drug repositioning approach identifies antidepressants as potent inhibitors of neuroendocrine tumors. Cancer Discovery, Volume (12), 1364-70.

Chuang CH, Yang D, Bai G, Freeland A, Pruitt SC, Schimenti JC. (2012) Post-transcriptional homeostasis and regulation of MCM2-7 in mammalian cells. Nucleic Acids Research, Volume 40(11), 4914-24.

bottom of page