Overview: Research in our lab aims to unravel the molecular and cellular principles governing gene regulation and nuclear architecture, and to translate these insights into improved therapeutic strategies for cancer. Our work is separated into two interconnected areas: (i) research exploring the fundamental mechanisms of transcription regulation and RNA biology, and (ii) examining how these processes are altered in cancer and how such dysregulation can be exploited to develop more effective treatment and prognosis for solid tumors. We employ a multidisciplinary approach integrating next-generation sequencing, high-resolution microscopy, biophysics, biochemistry, and computational biology.
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Figure 1A
Figure 1B
Condensate perspectives on signal-induced gene control and cancer therapeutics
Mammalian cells respond to environmental cues by initiating a cascade of reactions culminating in the assembly of transcription complexes at gene regulatory elements. Emerging evidence indicates that the chromatin-bound transcriptional apparatus behaves as a dynamic liquid droplet in vivo (biomolecular condensates). The condensate model of transcription offers additional layers for gene regulation, such as modulation of the emergent properties of condensates (material properties) and acting as a solid-state platform that facilitates long-distance genomic interactions, such as enhancer-promoter and enhancer-enhancer interactions (Figure 1A and B). The putative architectural features of transcriptional condensates are disordered domains of transcription regulators and RNAs. A primary focus in the lab is to dissect the roles of both components in hormone-induced gene regulation. We also study how mutations and aberrant protein expression alter condensate properties, nuclear compartmentalization, and responses to anticancer therapeutics. You can read more about our thoughts on these topics here:
https://pubmed.ncbi.nlm.nih.gov/35811173/
https://pubmed.ncbi.nlm.nih.gov/30833784/
Leveraging small-Molecule interactions with the transcriptome to innovate cancer therapy and prognosis
Most anticancer drugs used today are small molecules designed to target proteins or DNA. Yet RNA is far more abundant in cells and plays central roles in homeostasis and diseases. Our work is driven by the idea that the cancer transcriptome represents a vast and largely untapped therapeutic landscape. A primary focus of the lab is developing new technologies to map RNA interactions of clinically used cancer drugs. By combining click chemistry with next-generation sequencing, we created an open-ended RNA–small molecule mapping platform (PlatRNA-seq). Using this approach, we discovered that the widely used chemotherapeutic drug cisplatin binds specific RNA structures that modulate its pharmacology and have prognostic significance. We hypothesize that RNAs are not passive off-targets but active participants in drug response. We try to uncover how cells respond to drug-bound RNAs and to develop RNA- and condensate-centric strategies to overcome therapeutic limitations and advance precision cancer therapy.
References:
https://www.biorxiv.org/content/10.64898/2025.12.20.694502v1
Genome organization and nuclear architecture in gene regulation and cancer
The mammalian genome is hierarchically organized into distinct compartments (E.g., topologically associated domains (TADs), separated by TAD boundaries, whose architecture is still not fully understood. We found that regions of intense transcription play a direct role in maintaining genome structure. By selectively disrupting transcription-associated nuclear assemblies through chemical disruption of condensates (using 1,6-hexanediol), we found that a substantial fraction of TAD boundaries, particularly those linked to highly active genes and nuclear speckles, were weakened. These findings show that genome organization is not only scaffolded by structural proteins (E.g., CTCF, cohesins) but also by active transcription, nuclear condensates, and RNA scaffolds. We examine the roles of nuclear condensates and RNAs in signal-induced spatial gene regulation and in the underlying causes of cancer development and therapeutic outcomes.
References:
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