Breadcrumb

Daniel R. Larson, Ph.D.

Daniel R. Larson, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute

RESEARCH SUMMARY

The primary goal of Dan Larson's laboratory is to understand gene expression in eukaryotic cells, starting from the mechanistic behavior of individual macromolecules and proceeding to their regulation in cells and tissue. The laboratory utilizes a battery of biophysical, molecular and genomic approaches, including single-molecule microscopy, RNA visualization in fixed and living cells, computational modeling of gene regulation, and nascent RNA sequencing. Dr. Larson helped pioneer in vivo single-molecule studies of transcription and splicing. The view that has emerged from these studies is that gene regulation is a dynamic process resulting in stochastic variation within populations. Current work is focused on applying these experimental and theoretical approaches to the study of hematopoiesis in health and disease through the trans-NIH Myeloid Malignancies Program.

Areas of Expertise

1) transcription 2) splicing 3) single-molecule microscopy 4) RNA 5) stochastic gene expression 6) non-coding RNA 7) myeloid malignancy 8) post-transcriptional regulation

Myeloid Malignancies Program

A trans-NIH multidisciplinary network of researchers and clinicians dedicated to improving early detection, diagnosis, prognosis and development of novel therapeutics for myeloid malignancies.

Publications

Selected Key Publications

Dynamic imaging of nascent RNA reveals general principles of transcription dynamics and stochastic splice site selection

Wan Y, Anastasakis DG, Rodriguez J, Palangat M, Gudla P, Zaki G, Tandon M, Pegoraro G, Chow CC, Hafner M, Larson DR
Cell. May 4;. doi: 10.1016/j.cell.2021.04.012.: 2021.
Full-Text Article
[ Journal Article ]

Ribosome biogenesis is a downstream effector of the oncogenic U2AF1-S34F mutation

Akef A, McGraw K, Cappell SD, Larson DR.
PLoS Biol.. Nov;18(11):: e3000920, 2020.
Full-Text Article
[ Journal Article ]

Intrinsic Dynamics of a Human Gene Reveal the Basis of Expression Heterogeneity.

Rodriguez J, Ren G, Day CR, Zhao K, Chow CC, Larson DR.
Cell. 176: 213-226, 2019. [ Journal Article ]

The splicing factor U2AF1 contributes to cancer progression through a noncanonical role in translation regulation.

Palangat M, Anastasakis DG, Fei DL, Lindblad KE, Bradley R, Hourigan CS, Hafner M, Larson DR.
Genes and Development. 118: 10.1101/gad.319590, 2019. [ Journal Article ]

Single-Molecule Imaging Reveals a Switch between Spurious and Functional ncRNA Transcription

Lenstra TL, Coulon A, Chow CC, Larson DR.
Mol Cell. 60: 597-610, 2015. [ Journal Article ]

Job Vacancies

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Covers

MYC expression in single cells

MYC amplifies gene expression through global changes in transcription factor dynamics

Published Date

On the cover: In this issue, Patange et al. used optogenetics and fluorescence microscopy to demonstrate how the MYC oncogene amplifies transcription genome-wide by globally altering the dwell times of transcription factors. The cover depicts a microscope image of human osteosarcoma cells expressing high levels of MYC, where cell nuclei (purple) are in various states of transcribing a gene into RNA (gold). This snapshot captures an active transcription site in the center nucleus. Image by Simona Patange.

Citation

Patange S, Ball DA, Wan Y, Karpova TS, Girvan M, Levens D, Larson DR. 2022. MYC amplifies gene expression through global changes in transcription factor dynamics. Cell Reports 38.