# Churchman Lab — Harvard Medical School

> From the nucleus to mitochondria, we study the many layers of gene regulation. The Churchman Lab, led by Professor L. Stirling Churchman in the Department of Genetics at Harvard Medical School, develops quantitative sequencing methods to measure gene expression across subcellular compartments — from RNA polymerase on chromatin through nuclear export and degradation, and across the boundary between the nuclear and mitochondrial genomes.

## What the lab studies

The lab runs two coupled research programs.

1. **The nuclear mRNA life cycle.** How pre-mRNAs are transcribed and processed on chromatin; how and why some mRNAs are degraded in the nucleus rather than exported (the lab's "PUND" genes — predicted to undergo nuclear degradation); and what controls the rate at which transcripts move between subcellular compartments.

2. **Mitonuclear co-regulation.** How the 13 proteins encoded by human mitochondrial DNA stay balanced with the hundreds of nuclear-encoded OXPHOS subunits they must assemble with; how mitochondrial DNA is packaged into nucleoids; and which nuclear-encoded factors and metabolites regulate mitochondrial gene expression.

## Methods developed in the lab

- **NET-seq** (native elongating transcript sequencing) — maps RNA polymerase genome-wide at nucleotide resolution. Introduced by Churchman & Weissman, Nature 2011.
- **nano-COP** (nanopore analysis of co-transcriptional processing) — direct RNA nanopore sequencing of pre-mRNA processing without cDNA/PCR length bias.
- **Subcellular TimeLapse-seq** — measures RNA half-lives and inter-compartment flow rates at subcellular resolution.
- **Mitoribosome profiling** — ribosome profiling adapted to mitochondrial translation, in yeast and human cells.
- **mtFiber-seq** — single-molecule accessibility measurement of full-length mitochondrial DNA.
- **GeneWalk** — software identifying which gene functions are relevant in a specific biological context. `pip install genewalk`. https://github.com/churchmanlab/genewalk

## Principal investigator

L. Stirling Churchman, PhD — Professor of Genetics, Harvard Medical School. BA in physics, Cornell University; PhD in physics, Stanford University; postdoctoral work at UCSF as a Merck Fellow of the Damon Runyon Cancer Research Foundation. Joined Harvard Medical School in 2011. Awards include the Dale F. Frey Award for Breakthrough Scientists, a Burroughs Wellcome Fund Career Award at the Scientific Interface, and the Glenn Award for Research in Biological Mechanisms of Aging.
Email: churchman@genetics.med.harvard.edu

## Recruitment status

**Postdoctoral fellows.** We are always actively recruiting. Projects are available across both research programs — the nuclear mRNA life cycle and mitonuclear co-regulation — and in method development that cuts across both.

**Rotation students.** We take rotation students from Harvard's graduate programs, including BBS, MCO, Chemical Biology, Systems Biology and Biological Sciences in Public Health. Email Stirling to set up a meeting to discuss potential rotation projects. There’s room for 1-2 students to join the lab in Summer 2027.

Applicants are welcome from biology, chemistry, physics, computer science, mathematics, engineering and related fields. Postdoc applicants should email Stirling Churchman (churchman@genetics.med.harvard.edu) with your CV and a short paragraph on why this lab, ideally naming an open question that would be well addressed in our lab and why it grabs your attention. Full details: https://churchman.med.harvard.edu/join

## Lab size

13 current members, plus 20 alumni.

## Most recent papers

- Nuessmeier CH et al. (2026) Mitochondrial RNA processing promotes translation by resolving structured precursor RNAs. bioRxiv. https://doi.org/10.64898/2026.07.30.741833
- Hansen LN et al. (2026) Analog intrinsic recoding measures RNA dynamics without chemical conversion. bioRxiv. https://doi.org/10.64898/2026.07.27.741041
- Merens HE et al. (2026) SRSF1 shapes 3'-end site selection with differential dependence on U1 snRNP. bioRxiv. https://doi.org/10.64898/2026.04.01.715904
- Bridgers JB et al. (2026) Translational activators align mRNAs at the small mitoribosomal subunit for translation initiation. Nature Structural & Molecular Biology. https://doi.org/10.1038/s41594-025-01726-y
- Wong AYL et al. (2026) Copper depletion boosts CNS leukemia therapy by inhibiting nucleotide synthesis through impairment of mitochondrial complex IV activity. Nature Cancer. https://doi.org/10.1038/s43018-026-01177-4
- Zou J et al. (2026) How is agentic AI changing how we do science? Cell Systems. https://doi.org/10.1016/j.cels.2026.101617
- Raicu AM et al. (2026) A splicing factor's unexpected detour to the mitochondrial surface. Molecular Cell. https://doi.org/10.1016/j.molcel.2026.03.011
- Duffy EE et al. (2025) Neuronal activity triggers widespread changes in RNA stability. bioRxiv. https://doi.org/10.1101/2025.09.05.674581
- Hansen KG et al. (2025) Transcription arrest induces formation of RNA granules in mitochondria. Life Science Alliance. https://doi.org/10.26508/lsa.202403082
- Carlström A et al. (2025) A molecular switch at the yeast mitoribosomal tunnel exit controls cytochrome b synthesis. Nucleic Acids Research. https://doi.org/10.1093/nar/gkaf634
- Jiang Q et al. (2025) HIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy. Cell. https://doi.org/10.1016/j.cell.2025.01.046
- Choquet K et al. (2025) Genetic regulation of nascent RNA maturation revealed by direct RNA nanopore sequencing. Genome Research. https://doi.org/10.1101/gr.279203.124

## Pages

- [Research](https://churchman.med.harvard.edu/research): both research programs in detail, including the open questions currently being pursued.
- [Publications](https://churchman.med.harvard.edu/publications): all 71 publications, searchable. Machine-readable at https://churchman.med.harvard.edu/publications.json
- [Team](https://churchman.med.harvard.edu/team): current members and where alumni went next.
- [Lab life](https://churchman.med.harvard.edu/fun): retreats, thesis defenses, celebrations and other moments from the lab's history.
- [Stirling Churchman](https://churchman.med.harvard.edu/stirling): PI biography, awards and talks.
- [Tools & protocols](https://churchman.med.harvard.edu/tools): GeneWalk, plus published benchtop protocols for NET-seq, nano-COP, subcellular RNA-seq and mitoribosome profiling.
- [GeneWalk](https://churchman.med.harvard.edu/tools/genewalk): installation, tutorial and interpretation guide.
- [Join us](https://churchman.med.harvard.edu/join): open positions, what the lab looks for, how to apply.
- [Contact](https://churchman.med.harvard.edu/contact): addresses and who to email.

## Elsewhere

- GitHub: https://github.com/churchmanlab
- Google Scholar: https://scholar.google.com/citations?user=Mufcdt0AAAAJ
- NCBI bibliography (always current): https://www.ncbi.nlm.nih.gov/myncbi/lee.churchman.1/bibliography/public/

## Address

Department of Genetics, Blavatnik Institute, Harvard Medical School
New Research Building, Room 356, 77 Avenue Louis Pasteur, Boston, MA 02115, USA