About

Dr. Erica Larschan is an associate professor of biology at Brown University, where she has been teaching and conducting research for 16 years. Her research group focuses on understanding the complex process by which genes are regulated together within diverse and highly compacted genomes. The lab's work has been recognized with several significant awards, including the Presidential Early Career Award from President Obama. Dr. Larschan's research aims to elucidate the mechanisms of gene regulation in compacted genomic contexts, contributing to the broader understanding of genome function and regulation.

Research topics

• Genetics
• Computational biology
• Biology
• Evolutionary biology
• Cell biology

Selected publications

• The CLAMP GA-binding transcription factor regulates heat stress-induced transcriptional repression

  eLife · 2026-03-31

  articleOpen accessSenior author

  To survive exposure to heat stress (HS), organisms activate stress response genes and repress constitutive gene expression, thereby preventing the accumulation of potentially toxic RNA and protein products. Although many studies have elucidated the mechanisms that drive HS-induced activation of stress response genes across species, little is known about the mechanisms that repress constitutively expressed genes. Using nascent RNA-sequencing, we identify the first reported transcription factor (TF) that regulates repression of constitutive genes upon heat stress across species and define direct and indirect mechanisms of action by integrating 3D genomic approaches. We demonstrate that the CLAMP (Chromatin-linked adaptor for MSL complex proteins) GA-binding transcription factor (TF) regulates ∼75% of the HS-induced repression in Drosophila, a well-established model for understanding the mechanisms of HS-induced gene regulation. Using Micro-C, we demonstrate that heat stress induces widespread changes in local 3D chromatin looping, which are significantly associated with HS-induced transcriptional changes. Overall, we identify CLAMP as the first reported TF that induces HS repression, which modulates 3D chromatin looping through both direct mechanisms and indirect mechanisms. Moreover, we present the highest-resolution heat stress 3D genomic dataset available in Drosophila, providing a key resource for generating mechanistic insights into how temperature regulates 3D genomic contacts.

  PublisherDOI

• Reviewer #3 (Public review): The CLAMP GA-binding transcription factor regulates heat stress-induced transcriptional repression

  2026-03-31

  peer-reviewOpen accessSenior author

  To survive exposure to heat stress (HS), organisms activate stress response genes and repress constitutive gene expression, thereby preventing the accumulation of potentially toxic RNA and protein products. Although many studies have elucidated the mechanisms that drive HS-induced activation of stress response genes across species, little is known about the mechanisms that repress constitutively expressed genes. Using nascent RNA-sequencing, we identify the first reported transcription factor (TF) that regulates repression of constitutive genes upon heat stress across species and define direct and indirect mechanisms of action by integrating 3D genomic approaches. We demonstrate that the CLAMP (Chromatin-linked adaptor for MSL complex proteins) GA-binding transcription factor (TF) regulates ∼75% of the HS-induced repression in Drosophila, a well-established model for understanding the mechanisms of HS-induced gene regulation. Using Micro-C, we demonstrate that heat stress induces widespread changes in local 3D chromatin looping, which are significantly associated with HS-induced transcriptional changes. Overall, we identify CLAMP as the first reported TF that induces HS repression, which modulates 3D chromatin looping through both direct mechanisms and indirect mechanisms. Moreover, we present the highest-resolution heat stress 3D genomic dataset available in Drosophila, providing a key resource for generating mechanistic insights into how temperature regulates 3D genomic contacts.

  PublisherDOI

• The CLAMP GA-binding transcription factor regulates heat stress-induced transcriptional repression

  eLife · 2026-03-31

  articleOpen accessSenior author

  To survive exposure to heat stress (HS), organisms activate stress response genes and repress constitutive gene expression, thereby preventing the accumulation of potentially toxic RNA and protein products. Although many studies have elucidated the mechanisms that drive HS-induced activation of stress response genes across species, little is known about the mechanisms that repress constitutively expressed genes. Using nascent RNA-sequencing, we identify the first reported transcription factor (TF) that regulates repression of constitutive genes upon heat stress across species and define direct and indirect mechanisms of action by integrating 3D genomic approaches. We demonstrate that the CLAMP (Chromatin-linked adaptor for MSL complex proteins) GA-binding transcription factor (TF) regulates ∼75% of the HS-induced repression in Drosophila, a well-established model for understanding the mechanisms of HS-induced gene regulation. Using Micro-C, we demonstrate that heat stress induces widespread changes in local 3D chromatin looping, which are significantly associated with HS-induced transcriptional changes. Overall, we identify CLAMP as the first reported TF that induces HS repression, which modulates 3D chromatin looping through both direct mechanisms and indirect mechanisms. Moreover, we present the highest-resolution heat stress 3D genomic dataset available in Drosophila, providing a key resource for generating mechanistic insights into how temperature regulates 3D genomic contacts.

  PublisherOA PDFDOI

• Differential chromatin looping regulated by two GA-binding transcription factors creates an X-specific chromatin environment for dosage compensation

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-14

  articleOpen accessSenior authorCorresponding

  Abstract The mechanisms by which differential occupancy of transcription factors (TFs) at similar binding sites leads to context-specific targeting of large transcription complexes remain poorly understood. X chromosome upregulation (XCU), the most highly conserved step in dosage compensation and best studied in Drosophila , serves as a model for understanding how differential occupancy of similar TFs functions context-specifically. Sequence variation within GA-repeat motifs that accumulated on the X chromosome over evolutionary time promotes the binding of a specific GA-binding TF (CLAMP) that recruits the dosage compensation complex (DCC) while outcompeting another similar TF (GAF). However, the mechanism by which CLAMP-GAF competition drives specific targeting of the DCC to the X chromosome remains unknown. Because DCC binding sites cluster in 3D space, we combined Micro-C and Hi-ChIP to determine that CLAMP and GAF directly mediate largely mutually exclusive 3D genomic contacts. Specifically, we show that CLAMP but not GAF drives local short-range interactions that directly link high affinity DCC binding sites with active, dosage-compensated housekeeping genes. In contrast, GAF mediates interactions between transcriptionally silent insulator regions on the X chromosome spanning a wider range of genomic distances. Together, these findings demonstrate that CLAMP outcompetes GAF at active regions on the X chromosome, but not autosomes, to create an X-chromosome specific chromatin environment for dosage compensation. Overall, we provide new insight into how differential TF binding at similar binding sites drives context-specific targeting of transcription complexes.

  PublisherDOI

• An snRNA-seq aging clock for the fruit fly head sheds light on sex-biased aging

  Scientific Reports · 2026-04-14

  articleOpen access

  Although multiple high-performing epigenetic aging clocks exist, few are based directly on gene expression. Such transcriptomic aging clocks allow us to identify potential age-associated genes directly. However, most existing transcriptomic clocks model a subset of genes and are limited in their ability to predict novel biomarkers. With the growing application of single-cell sequencing, there is a need for robust single-cell transcriptomic aging clocks. Moreover, aging clocks have yet to be applied to investigate the elusive phenomenon of sex differences in aging. We introduce TimeFlies, a pan-cell-type snRNA-seq aging clock for the Drosophila melanogaster head. TimeFlies uses deep learning to classify the donor age of cells based on genome-wide gene expression profiles. Using explainability methods, we identified key marker genes contributing to the classification, with lncRNAs showing up as highly enriched among predicted biomarkers. lncRNA:roX1 and lncRNA:roX2 are top clock genes across cell types. Both are regulators of X chromosome dosage compensation, a pathway previously found to be significantly affected by aging in the mouse brain. We validated these findings experimentally in Drosophila, showing a decrease in survival when dosage compensation is inhibited in vivo. Furthermore, we trained sex-specific TimeFlies clocks and noted significant differences in model predictions and explanations between male and female clocks, suggesting that different pathways drive aging in males and females.

  PublisherOA PDFDOI

• Reviewer #2 (Public review): The CLAMP GA-binding transcription factor regulates heat stress-induced transcriptional repression

  2026-03-31

  peer-reviewOpen accessSenior author

  To survive exposure to heat stress (HS), organisms activate stress response genes and repress constitutive gene expression, thereby preventing the accumulation of potentially toxic RNA and protein products. Although many studies have elucidated the mechanisms that drive HS-induced activation of stress response genes across species, little is known about the mechanisms that repress constitutively expressed genes. Using nascent RNA-sequencing, we identify the first reported transcription factor (TF) that regulates repression of constitutive genes upon heat stress across species and define direct and indirect mechanisms of action by integrating 3D genomic approaches. We demonstrate that the CLAMP (Chromatin-linked adaptor for MSL complex proteins) GA-binding transcription factor (TF) regulates ∼75% of the HS-induced repression in Drosophila, a well-established model for understanding the mechanisms of HS-induced gene regulation. Using Micro-C, we demonstrate that heat stress induces widespread changes in local 3D chromatin looping, which are significantly associated with HS-induced transcriptional changes. Overall, we identify CLAMP as the first reported TF that induces HS repression, which modulates 3D chromatin looping through both direct mechanisms and indirect mechanisms. Moreover, we present the highest-resolution heat stress 3D genomic dataset available in Drosophila, providing a key resource for generating mechanistic insights into how temperature regulates 3D genomic contacts.

  PublisherDOI

• Gene dosage: Polyploidy protects against lethal X-dosage imbalance in male Drosophila

  Current Biology · 2026-03-01

  articleSenior author
  PublisherDOI

• Reviewer #1 (Public review): The CLAMP GA-binding transcription factor regulates heat stress-induced transcriptional repression

  2026-03-31

  peer-reviewOpen accessSenior author

  To survive exposure to heat stress (HS), organisms activate stress response genes and repress constitutive gene expression, thereby preventing the accumulation of potentially toxic RNA and protein products. Although many studies have elucidated the mechanisms that drive HS-induced activation of stress response genes across species, little is known about the mechanisms that repress constitutively expressed genes. Using nascent RNA-sequencing, we identify the first reported transcription factor (TF) that regulates repression of constitutive genes upon heat stress across species and define direct and indirect mechanisms of action by integrating 3D genomic approaches. We demonstrate that the CLAMP (Chromatin-linked adaptor for MSL complex proteins) GA-binding transcription factor (TF) regulates ∼75% of the HS-induced repression in Drosophila, a well-established model for understanding the mechanisms of HS-induced gene regulation. Using Micro-C, we demonstrate that heat stress induces widespread changes in local 3D chromatin looping, which are significantly associated with HS-induced transcriptional changes. Overall, we identify CLAMP as the first reported TF that induces HS repression, which modulates 3D chromatin looping through both direct mechanisms and indirect mechanisms. Moreover, we present the highest-resolution heat stress 3D genomic dataset available in Drosophila, providing a key resource for generating mechanistic insights into how temperature regulates 3D genomic contacts.

  PublisherDOI

• Optimal transport reveals dynamic gene regulatory networks via gene velocity estimation

  PLoS Computational Biology · 2025-05-08 · 7 citations

  articleOpen access

  Inferring gene regulatory networks from gene expression data is an important and challenging problem in the biology community. We propose OTVelo, a methodology that takes time-stamped single-cell gene expression data as input and predicts gene regulation across two time points. It is known that the rate of change of gene expression, which we will refer to as gene velocity, provides crucial information that enhances such inference; however, this information is not always available due to the limitations in sequencing depth. Our algorithm overcomes this limitation by estimating gene velocities using optimal transport. We then infer gene regulation using time-lagged correlation and Granger causality via regularized linear regression. Instead of providing an aggregated network across all time points, our method uncovers the underlying dynamical mechanism across time points. We validate our algorithm on 13 simulated datasets with both synthetic and curated networks and demonstrate its efficacy on 9 experimental data sets.

  PublisherDOI

• Comparative transcriptomic analysis of embryonic stem cells across mammalian species

  iScience · 2025-12-24 · 1 citations

  articleOpen access

  pluripotency markers. Despite variability in gene expression dynamics, gene co-expression networks showed remarkable conservation across species. Among pluripotency states, the primed state demonstrated the highest conservation, evidenced by shared markers, preserved gene networks, and stronger selective pressures acting on its genes. These findings provide critical insights into the evolution and regulation of pluripotency, laying a foundation for refining stem cell models to enhance their translational potential in regenerative medicine, agriculture, and conservation biology.

  PublisherDOI

Recent grants

• NIH Grant R01GM098461

  NIH · $2.5M · 2018

• Establishment of Active Chromatin Domains

  NIH · $2.0M · 2018–2024

Frequent coauthors

• Peter J. Park

  Harvard University

  94 shared

• Mitzi I. Kuroda

  Brigham and Women's Hospital

  78 shared

• Michael Tolstorukov

  61 shared

• Artyom A. Alekseyenko

  47 shared

• William T. Jordan

  44 shared

• Youngsook L. Jung

  Boston Children's Museum

  42 shared

• Eric Bishop

  40 shared

• Shouyong Peng

  Ludong University

  38 shared

Labs

• The Larschan LabPI

  The Larschan Lab is focused on understanding the mechanisms of epigenetic regulation and how they contribute to development and disease.

Awards & honors

• Pew Biomedical Scholars program (2011-2015)
• NIH R01 GM098461-1 (2011-2016)
• Brown ADVANCE Grant from NSF HRD-0548311 (2010-2011)
• RI-INBRE NIH Seed Award P20RR016457-10