Dennis J. Yuan, PhD

Dennis J. Yuan, PhD

Postdoctoral Fellow
Weill Cornell Medicine & New York Genome Center
dyuan (at) nygenome.org

About

I am a postdoctoral fellow in the Landau Lab at Weill Cornell Medicine and the New York Genome Center, where I develop single-cell technologies that link mutations and cell states.

I trained as a biomedical engineer. My doctoral work at Columbia used engineered materials to probe how mechanical cues shape T cell activation, which is where my interest in single-cell heterogeneity started.

Research

1Single-cell genotype-to-phenotype mapping in normal tissues

Somatic mutations accumulate in every tissue as we age, and a key insight is how a genotype contributes to cell state and behavior. We built scG2P to co-capture somatic DNA mutations and mRNA transcripts from the same cell at scale. Applied to esophageal tissue from older adults, more than half of cells carried clonal driver mutations. In this mutation landscape, we revealed that NOTCH1- and TP53-mutant clones disproportionately occupy immature differentiation states, staying in the tissue and continuing to divide instead of maturing and shedding from the surface.

  • Genotype-to-phenotype mapping of somatic clonal mosaicism via single-cell co-capture of DNA mutations and mRNA transcripts Cancer Discov 2026 PaperPreprintPress

2Retracing evolutionary histories in aging and pre-cancerous tissues

Clonal competition occurs in normal tissue over decades. Using large-scale single-cell phylogenetics, we reconstruct a timeline of when clones arose, which mutations initiated expansion and which genetic events follow, and how fast clones expanded, turning a static snapshot of mutations into a history of the tissue.

  • Large-scale single-cell phylogenetic mapping of clonal evolution in the human aging esophagus bioRxiv 2025 Preprint

3Somatic mosaicism across tissues (SMaHT Network)

As part of the NIH Somatic Mosaicism across Human Tissues (SMaHT) Network, we contribute single-cell DNA sequencing to a community effort to catalog somatic mutations across the human body — benchmarking how well different sequencing technologies and analysis methods detect them, and mapping mosaicism cell by cell across tissues.

  • Comprehensive benchmarking of somatic mutation detection by the SMaHT Network Cell 2026 PaperPreprint
  • A comprehensive view of somatic mosaicism by single-cell DNA analysis bioRxiv 2025 Preprint
  • The Somatic Mosaicism across Human Tissues Network Nature 2025 Paper

4Earlier work — T cell mechanobiology

My doctoral work at Columbia asked how the physical properties of an antigen-presenting surface shape a T cell’s response. T cell activation turns out to be biphasic in substrate stiffness, and soft elastomer fiber scaffolds can expand T cells from patients whose cells expand poorly by conventional methods — a route to personalizing cell therapy manufacturing.

  • Biphasic response of T cell activation to substrate stiffness Biomaterials 2021 Paper
  • Enhanced activation and expansion of T cells using mechanically soft elastomer fibers Adv Biosyst 2018 Paper
  • Improving T cell expansion with a soft touch Nano Lett 2017 Paper

News

Cover of Cancer Discovery volume 16 issue 4
Featured on the cover of Cancer Discovery 16(4), April 2026

Cover image reproduced from Cancer Discovery 16(4), © American Association for Cancer Research. Artwork by Bianca Dunn.

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Publications

Newest first. Also on Google Scholar.

Selected publications

First-author and equal-contribution papers.

  1. Genotype-to-phenotype mapping of somatic clonal mosaicism via single-cell co-capture of DNA mutations and mRNA transcripts
    Yuan DJ, Zinno J, Botella T, Dhingra D, Wang S, Hawkins AG, Swett A, Sotelo J, Raviram R, Hughes C, Potenski C, Godfrey KD, Ainsworth KM, Xu S, Que J, Abrams JA, Yokoyama A, Kakiuchi N, Ogawa S, Landau DA
    Cancer Discovery, 2026
    PaperPreprintPress
  2. Large-scale single-cell phylogenetic mapping of clonal evolution in the human aging esophagus
    Prieto T*, Yuan DJ*, Zinno J, Hughes C, Midler N, Kao S, Huuhtanen J, Raviram R, Fotopoulou F, Ruthen N, Rajagopalan S, Schiffman JS, D'Avino AR, Yoon SH, Sotelo J, Omans ND, Wheeler N, Garces A, Pradhan B, Cheng AP, Robine N, Potenski C, Godfrey K, Kakiuchi N, Yokoyama A, Ogawa S, Abrams J, Raimondi I, Landau DA
    *Contributed equally
    bioRxiv (preprint), 2025
    Preprint
  3. Biphasic response of T cell activation to substrate stiffness
    Yuan DJ, Shi L, Kam LC
    Biomaterials, 273:120797, 2021
    Paper

All publications

  1. Comprehensive benchmarking of somatic mutation detection by the SMaHT Network
    Abyzov A, Natu A, Voshall A, Sedeño-Cortés AE, Burn AH, Boyle AP, et al., Yuan DJ, et al., SMaHT Network
    Cell, 189(21):6594-6612, 2026
    PaperPreprint
  2. Genotype-to-phenotype mapping of somatic clonal mosaicism via single-cell co-capture of DNA mutations and mRNA transcripts
    Yuan DJ, Zinno J, Botella T, Dhingra D, Wang S, Hawkins AG, Swett A, Sotelo J, Raviram R, Hughes C, Potenski C, Godfrey KD, Ainsworth KM, Xu S, Que J, Abrams JA, Yokoyama A, Kakiuchi N, Ogawa S, Landau DA
    Cancer Discovery, 2026
    PaperPreprintPress
  3. A comprehensive view of somatic mosaicism by single-cell DNA analysis
    Luquette LJ, Coorens THH, Natu A, Suvakov M, Caplin A, Jun MS, Mo A, Pelt J, Anderson L, Berselli M, Bhamidipati S, Blanchard T, Brew J, Chun HE, Chun H, Dehankar MK, Feng WC, Furatero R, Grochowski CM, Ho E, Jang Y, Kottapalli K, Leonard MK, Lim NS, Lindsay T, Nicholson S, Raimondi I, Runnels A, Scharlee C, Shin J, Veit AD, VonDran M, Wang Y, Yuan DJ, Zhao Y, SMaHT Single Cell Focus Group, Bell TJ, Ardlie K, Doddapaneni H, Fulton R, Germer S, Landau D, Oh JW, Park PJ, Vaccarino FM, Walsh C, Abyzov A
    bioRxiv (preprint), 2025
    Preprint
  4. Large-scale single-cell phylogenetic mapping of clonal evolution in the human aging esophagus
    Prieto T*, Yuan DJ*, Zinno J, Hughes C, Midler N, Kao S, Huuhtanen J, Raviram R, Fotopoulou F, Ruthen N, Rajagopalan S, Schiffman JS, D'Avino AR, Yoon SH, Sotelo J, Omans ND, Wheeler N, Garces A, Pradhan B, Cheng AP, Robine N, Potenski C, Godfrey K, Kakiuchi N, Yokoyama A, Ogawa S, Abrams J, Raimondi I, Landau DA
    *Contributed equally
    bioRxiv (preprint), 2025
    Preprint
  5. Paired plus-minus sequencing is an ultra-high throughput and accurate method for dual strand sequencing of DNA molecules
    Cheng AP, Rusinek I, Sossin A, Widman AJ, Meiri E, Krieger G, Hirschberg O, Tov DS, Gilad S, Jaimovich A, Barad O, Avaylon S, Rajagopalan S, Potenski C, Prieto T, Yuan DJ, et al., Faltas BM, Landau DA
    bioRxiv (preprint), 2025
    Preprint
  6. The Somatic Mosaicism across Human Tissues Network
    Coorens THH, Oh JW, Choi YA, Lim NS, Zhao B, Voshall A, Abyzov A, et al., Vaccarino FM, SMaHT Network (incl. Yuan DJ)
    Nature, 643(8070):47-59, 2025
    Paper
  7. Measuring longitudinal genome-wide clonal evolution of pediatric acute lymphoblastic leukemia at single-cell resolution
    Pang Y, Prieto T, Gonzalez-Pena V, Aragon A, Xia Y, Kao S, Rajagopalan S, Zinno J, Quentin J, Laval J, Yuan DJ, Omans N, Klein D, MacKay M, De Vlaminck I, Easton J, Evans W, Landau DA, Gawad C
    bioRxiv (preprint), 2025
    Preprint
  8. Programmable endonuclease combined with isothermal polymerase amplification to selectively enrich for rare mutant allele fractions
    Chen J, Qiu T, Mauk MG, Su Z, Fan Y, Yuan DJ, Zhou Q, Qiao Y, Bau HH, Ying J, Song J
    Chinese Chemical Letters, 33(8):4126-4132, 2022
    Paper
  9. Biphasic response of T cell activation to substrate stiffness
    Yuan DJ, Shi L, Kam LC
    Biomaterials, 273:120797, 2021
    Paper
  10. Enhanced activation and expansion of T cells using mechanically soft elastomer fibers
    Dang A, De Leo S, Bogdanowicz DR, Yuan DJ, Fernandes SM, Brown JR, Lu HH, Kam LC
    Advanced Biosystems, 2(2):1700167, 2018
    Paper
  11. Improving T cell expansion with a soft touch
    Lambert L, Goebrecht GKE, De Leo SE, O'Connor RS, Nunez-Cruz S, Li T, Yuan J, Milone MC, Kam LC
    Nano Letters, 17(2):821-826, 2017
    Paper
  12. Astrocyte elevated gene-1 (AEG-1) induces epithelial-mesenchymal transition in lung cancer through activating Wnt/beta-catenin signaling
    He W, He S, Wang Z, Shen H, Fang W, Zhang Y, Qian W, Lin M, Yuan J, Wang J, Huang W, Wang L, Ke Z
    BMC Cancer, 15(1):107, 2015
    Paper

Background

Appointments

  • 2026–presentMacMillan Fellow
    MacMillan Center for the Study of the Non-coding Cancer Genome
    New York Genome Center
  • 2021–presentPostdoctoral Fellow
    Weill Cornell Medicine & New York Genome Center
    Landau Lab (Dan Landau, MD PhD)
  • 2017–2020TL1 Precision Medicine Fellow
    Irving Institute for Clinical and Translational Research, CUIMC

Education

  • 2017–2021PhD, Biomedical Engineering
    Columbia University
    Thesis: Mechanical regulation of T cell activation (Lance Kam, PhD)
  • 2015–2017MSc, Biomedical Engineering
    Columbia University
  • 2011–2015BSc, Bioengineering, magna cum laude
    University of California, Los Angeles

Awards

  • 2026–presentMacMillan Postdoctoral Fellowship
    MacMillan Center for the Study of the Non-coding Cancer Genome, New York Genome Center
  • 2025Outstanding Contribution by a Postdoctoral Fellow
    New York Genome Center
  • 2017–2020NIH/NCATS TL1 Precision Medicine Fellowship

Contact

dyuan@nygenome.org
New York Genome Center, 101 Avenue of the Americas, New York, NY 10013

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