Rupa Sridharan

About

Professor Rupa Sridharan holds a Ph.D. from the University of California, Los Angeles, and completed postdoctoral research at the Eli and Edythe Broad Stem Cell Institute at UCLA. She leads the Sridharan Lab, which focuses on the epigenetic control of cell identity. The lab investigates mechanisms underlying cell identity and reprogramming, including the role of histone modifications and chromatin regulators in these processes. Professor Sridharan's research has contributed to understanding how epigenetic factors such as histone methylases and demethylases influence transcriptional regulation and pluripotency acquisition. Her lab has made discoveries related to the prevention of hypertranscription and hyperacetylation by the H3K79 methylase DOT1L, the coordination of histone and DNA demethylation during pluripotency acquisition, and the modulation of transcription elongation by heterochromatin protein 1 family members. The Sridharan Lab is actively engaged in training postdoctoral scholars, graduate students, and undergraduate researchers, advancing knowledge in cellular and molecular mechanisms that govern cell fate and identity.

Research topics

• Biology
• Cell biology
• Endocrinology
• Genetics
• Cancer research
• Immunology

Selected publications

• Inference of cell type-specific gene regulatory networks on cell lineages from single cell omic datasets

  Nature Communications · 2023-05-27 · 112 citations

  articleOpen access

  Cell type-specific gene expression patterns are outputs of transcriptional gene regulatory networks (GRNs) that connect transcription factors and signaling proteins to target genes. Single-cell technologies such as single cell RNA-sequencing (scRNA-seq) and single cell Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq), can examine cell-type specific gene regulation at unprecedented detail. However, current approaches to infer cell type-specific GRNs are limited in their ab…

  PublisherOA PDFDOI

• Methyl-Metabolite Depletion Elicits Adaptive Responses to Support Heterochromatin Stability and Epigenetic Persistence

  Molecular Cell · 2020 · 88 citations

  DOI

• HP1γ regulates H3K36 methylation and pluripotency in embryonic stem cells

  Nucleic Acids Research · 2020-10-28 · 27 citations

  articleOpen accessSenior author

  The heterochromatin protein 1 (HP1) family members are canonical effectors and propagators of gene repression mediated by histone H3 lysine 9 (H3K9) methylation. HP1γ exhibits an increased interaction with active transcription elongation-associated factors in embryonic stem cells (ESCs) compared to somatic cells. However, whether this association has a functional consequence remains elusive. Here we find that genic HP1γ colocalizes and enhances enrichment of transcription elongation-associated H…

  PublisherOA PDFDOI

• DOT1L inhibition enhances pluripotency beyond acquisition of epithelial identity and without immediate suppression of the somatic transcriptome

  Stem Cell Reports · 2022-01-06 · 23 citations

  articleOpen accessSenior authorCorresponding

  Inhibiting the histone 3 lysine 79 (H3K79) methyltransferase, disruptor of telomeric silencing 1-like (DOT1L), increases the efficiency of reprogramming somatic cells to induced pluripotent stem cells (iPSCs). Here, we find that, despite the enrichment of H3K79 methylation on thousands of actively transcribed genes in somatic cells, DOT1L inhibition (DOT1Li) does not immediately cause the shutdown of the somatic transcriptional profile to enable transition to pluripotency. Contrary to the preval…

  PublisherDOI

• Connecting the DOTs on Cell Identity

  Frontiers in Cell and Developmental Biology · 2022-06-06 · 18 citations

  reviewOpen accessSenior authorCorresponding

  DOT1-Like (DOT1L) is the sole methyltransferase of histone H3K79, a modification enriched mainly on the bodies of actively transcribing genes. DOT1L has been extensively studied in leukemia were some of the most frequent onco-fusion proteins contain portions of DOT1L associated factors that mislocalize H3K79 methylation and drive oncogenesis. However, the role of DOT1L in non-transformed, developmental contexts is less clear. Here we assess the known functional roles of DOT1L both in vitro cell…

  PublisherOA PDFDOI

Recent grants

• Collaboration of chromatin remodeling and signaling pathways in pluripotency

  NIH · $2.9M · 2015–2024

Frequent coauthors

• Sushmita Roy

  University of Wisconsin–Madison

  47 shared

• Alireza Fotuhi Siahpirani

  University of Tehran

  40 shared

• Kathrin Plath

  39 shared

• Stefan Pietrzak

  Wisconsin Institutes for Discovery

  31 shared

• Coral K. Wille

  Wisconsin Institutes for Discovery

  31 shared

• Sunnie Grace McCalla

  University of Wisconsin–Madison

  30 shared

• Shilu Zhang

  University of Science and Technology of China

  22 shared

• Spencer Halberg

  22 shared

Labs

• Sridharan LabPI

Similar researchers at University of Wisconsin-Madison

• Timothy J. Kamph-77
• Emery Bresnickh-60
• Ricki Colmanh-47