Yang Lab

Yang Lab

Principal Investigator 

Dian Yang, PhD 

Assistant Professor of Molecular Pharmacology and Therapeutics 

Location and Contact Information 

650 W 168th St., William Black Building, Room 7-705B

New York, NY 10032

dy2491@cumc.columbia.edu 

To learn more about the Yang Lab, please visit:  www.dianyanglab.com. 

Research Interests 

Mechanisms of tumor evolution, Genetically engineered mouse models of lung cancer development, Molecular recording technology development, Single cell genomics

Overview 

Dr. Yang completed his Ph.D. in cancer biology at Stanford University with Dr. Monte Winslow and Dr. Julien Sage. He was awarded the Denise Chan Outstanding Thesis Award for identifying the genetic and epigenetic mechanisms of how small cell lung cancer adopting neuronal migration machineries to metastasize. He then did his postdoc with Dr. Jonathan Weissman at MIT and developed a CRISPR-based evolving lineage tracing mouse model. This new mouse model enabled him to continuously track how a tumor evolves from a single transformed cell into an aggressive tumor and spreads systemically at an unprecedented resolution. His work to date has integrated CRISPR technologies, single-cell genomics, in vivo cancer modeling and computational analysis, providing a new paradigm to study tumor evolution. Dr. Yang recently won a Damon Runyon Jake Wetchler Award and a Dale F. Frey Award for Breakthrough Scientists.

To learn more about the Yang lab, please:  www.dianyanglab.com.  We are recruiting students, technicians and postdocs!

Research 

The Yang Lab generally interested in investigating the fundamental principles of tumor evolution and identifying key regulators of tumor progression. Our research is at the interface of cancer biology, technology development, and computational analysis, which combines CRISPR-based molecular recording tools, genetically engineered mouse models (GEMMs), single cell genomics-related algorithm development, and in vivo functional assays.

The main goal of the Yang Lab is to investigate the intrinsic and extrinsic mechanisms governing cancer cell state transitions and ultimately develop a quantitative roadmap of tumor evolution. Towards this goal, we have recently developed an autochthonous “KP-Tracer” mouse model, which allows us to continuously monitor the processes by which a single cell harboring oncogenic mutations evolves into an aggressive tumor. In collaboration with Nir Yosef's lab, we have developed a new computational algorithm "Cassiopeia" for building high-resolution tumor phylogenies. This offers a significant advance in tumor evolution modeling by enabling quantitative inference of fitness landscapes, cellular plasticity, evolutionary paths of primary tumors and metastases, and the role of any gene of interest in altering all these facets of tumor development. 

Building upon these cutting-edge technologies, our lab aims to develop a comprehensive understanding of tumor evolution by integrating multiple data modalities. We will dissect the cell-intrinsic and extrinsic mechanisms that govern cancer cell state transitions, and identify the regulatory gene networks that drive cancer evolution. Furthermore, our lab is committed to expanding the molecular recording toolkits, enabling more precise and detailed reconstruction of tumor life histories. Through these collaborative efforts, we strive to reconstruct the entire trajectory of tumor development, capturing the process from a single transformed cell to a complex and aggressive tumor population, with unprecedented scale and resolution. Ultimately, this holistic approach will pave the way for the development of predictive models of tumor evolution, advancing our ability to predict and potentially intervene in cancer progression.

Selected Awards 

2021  Damon Runyon Dale F. Frey Award for Breakthrough Scientists

2020  Jake Wetchler Award for Pediatric Innovation

2018  Damon Runyon Cancer Research Postdoctoral Fellowship Award

2018  Denise A. Chan Outstanding Thesis Award, Stanford University

2016  Best Speakers Prize, the 39th Stanford Cancer Biology Retreat

2015  Tobacco-Related Disease Research Program Dissertation Award

2011   Stanford Graduate Fellowship (Lucille P. Markey Biomedical Research Fellow)

2011   Magna Cum Laude, Cornell University

2011   High Honor Distinction in Research, Cornell University

2010   Howard Hughes Scholars Fellowship at Cornell University

2010   New York State Stem Cell Research Fellowship

Selected Publications 

  1. 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.
  2. Jones MG*, Yang D*, ^, Weissman JS^. (2022) New tools for lineage tracing in cancer in vivo. Annual Review of Cancer Biology. *Equal Contribution, ^Co-corresponding author.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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, Co-first author.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.

To learn more about the Yang lab, please:  www.dianyanglab.com.  We are recruiting students, technicians and postdocs!