About

Joonho Lee is an Assistant Professor of Chemistry and Chemical Biology at Harvard University, joining the faculty in July 2023. His research group develops and implements theoretical and computational methods to study a wide range of phenomena in nature, focusing on understanding interactions such as electron-electron, electron-vibration, vibration-photon, and electron-photon. The group's current emphasis includes developing quantum chemistry methods for condensed phase problems, creating quantum algorithms for chemical problems, computational modeling of electrocatalysis, and understanding perovskites for solar applications and moiré materials. These research directions aim to address energy and sustainability challenges as well as fundamental science questions. Joonho Lee completed his Ph.D. in chemistry at the University of California, Berkeley, under the guidance of Prof. Martin Head-Gordon. His main contributions during his doctoral work include the development of regularized perturbation theory, coupled-cluster valence bond theory for strong correlation, and an efficient quantum circuit ansatz for chemistry. His dissertation, titled Postmodern Electronic Structure Theory, was recognized by the 2020 Justin Jankunas Doctoral Dissertation Award in the American Physical Society. Since graduating in 2019, he has been a postdoctoral researcher in the Reichman group at Columbia University, developing expertise in materials, quantum dynamics, and vibronic problems. Additionally, he is a visiting faculty researcher at Google Quantum AI, where he develops and applies quantum algorithms for electronic structure problems.

Research topics

• Computational biology
• Genetics
• Computer Science
• Biology
• Cell biology
• Chemistry
• Biochemistry
• Mathematics
• Statistics

Selected publications

• Sirtuin 7 regulates dosage compensation and safeguards the female X-chromosome

  Zenodo (CERN European Organization for Nuclear Research) · 2026-04-07

  otherOpen access

  Downstream bioinformatics analysis related to publication. Code, datasets, used for analysis or RNA-seq data include DE, normalization, GSEA, figure generation (ecdf, scatterplots, others).

  PublisherDOI

• Sirtuin 7 regulates dosage compensation and safeguards the female X-chromosome

  Zenodo (CERN European Organization for Nuclear Research) · 2026-04-07

  otherOpen accessSenior author

  Downstream bioinformatics analysis related to publication. Code, datasets, used for analysis or RNA-seq data include DE, normalization, GSEA, figure generation (ecdf, scatterplots, others) contained in "code.tgz". Code and additional datasets used for analysis of ChIP-seq experiments is contained in "ChIP_analyses.tar.gz".

  PublisherDOI

• Cleavage region organizes the structural architecture of the SINE-derived B2 repressive ribozyme

  Communications Biology · 2026-03-23

  articleOpen access

  The SINE-encoded B2 retrotransposon is an RNA Polymerase III (POL-III)-derived transcript whose expression is substantially upregulated during various cellular stress responses. Beyond retrotransposition, the B2 non-coding RNA can directly bind and repress the activity of RNA Polymerase II (POL-II), leading to a significant downregulation of transcripts during stress. Notably, our recent findings have shown that B2 is a self-cleaving ribozyme whose activity can be induced by interactions with chromatin-modifying factors through non-canonical epigenetic mechanisms that co-regulate its function across distinct chromatin-binding target loci. Here, by integrating RNA chemical probing, small-angle X-ray scattering, and 3D motif modeling, we determine structural ensemble-to-function relations for the B2 SINE ribozyme RNA. Genetic perturbations of the RNA suggest that the B2 SINE ribozyme has a well-defined secondary and dynamic tertiary structure that depends on the integrity of the critical region, which confers ribozymatic activity and repressive extent by POL-II. Using an RNA engineering approach, we examine the effects of point mutations, deletions of the main cleavage site, and deletions of the cleavage domain on the structural ensemble of the RNA. Combining this approach with in vitro and in vivo functional perturbation methods highlights the relationships between structural ensembles and various biologically relevant functional outcomes.

  PublisherOA PDFDOI

• Sirtuin 7 regulates dosage compensation and safeguards the female X-chromosome

  Zenodo (CERN European Organization for Nuclear Research) · 2026-04-07

  otherOpen accessSenior author

  Downstream bioinformatics analysis related to publication. Code, datasets, used for analysis or RNA-seq data include DE, normalization, GSEA, figure generation (ecdf, scatterplots, others) contained in "code.tgz". Code and additional datasets used for analysis of ChIP-seq experiments is contained in "ChIP_analyses.tar.gz".

  PublisherDOI

• Corrigendum: Pharmacologically stabilizing RNA G-quadruplexes in coronavirus genome reduces infectivity

  RNA · 2025-11-17

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Author response: Xist RNA binds select autosomal genes and depends on Repeat B to regulate their expression

  2025-06-09

  peer-reviewOpen accessSenior author
  PublisherDOI

• A biophysical basis for the spreading behavior and limited diffusion of Xist

  Cell · 2025-01-16 · 19 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Jpx RNA controls Xist induction through spatial reorganization of the mouse X-inactivation center

  Developmental Cell · 2025-07-17 · 2 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Protocol for capturing a full transcriptome from single preimplantation embryos using So-Smart-seq

  STAR Protocols · 2025-01-05 · 1 citations

  articleOpen accessSenior authorCorresponding

  Strand-optimized Smart-seq (So-Smart-seq) can capture a comprehensive transcriptome from low-input samples. This technique detects both polyadenylated and non-polyadenylated RNAs, inclusive of repetitive RNAs, while excluding highly abundant ribosomal RNAs. So-Smart-seq preserves strand information and minimizes 5′ to 3′ coverage bias. We describe steps for the analysis of single mouse preimplantation embryos, including embryo isolation, library preparation, ribosomal cDNA depletion, and initial data processing. The protocol may be adapted for other low-input samples and the detection of small RNAs of <200 nt. For complete details on the use and execution of this protocol, please refer to Wei et al. 1 • Collection of preimplantation embryos from the oviduct and uterus of female mice • Capture of full transcriptome in a single preimplantation embryo by So-Smart-seq • Preparation of oligo probes to deplete ribosomal cDNAs from libraries • Pre-processing of raw sequencing data for downstream analyses Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics. Strand-optimized Smart-seq (So-Smart-seq) can capture a comprehensive transcriptome from low-input samples. This technique detects both polyadenylated and non-polyadenylated RNAs, inclusive of repetitive RNAs, while excluding highly abundant ribosomal RNAs. So-Smart-seq preserves strand information and minimizes 5′ to 3′ coverage bias. We describe steps for the analysis of single mouse preimplantation embryos, including embryo isolation, library preparation, ribosomal cDNA depletion, and initial data processing. The protocol may be adapted for other low-input samples and the detection of small RNAs of <200 nt.

  PublisherDOI

• Xist RNA binds select autosomal genes and depends on Repeat B to regulate their expression

  eLife · 2025-06-09 · 2 citations

  articleOpen accessSenior author

  Xist, a pivotal player in X chromosome inactivation (XCI), has long been perceived as a cis-acting long noncoding RNA that binds exclusively to the inactive X chromosome (Xi). However, Xist ’s ability to diffuse under select circumstances has also been documented, leading us to suspect that Xist RNA may have targets and functions beyond the Xi. Here, using female mouse embryonic stem cells (ES) and mouse embryonic fibroblasts (MEF) as models, we demonstrate that Xist RNA indeed can localize beyond the Xi. However, its binding is limited to ~100 genes in cells undergoing XCI (ES cells) and in post-XCI cells (MEFs). The target genes are diverse in function but are unified by their active chromatin status. Xist binds discretely to promoters of target genes in neighborhoods relatively depleted for Polycomb marks, contrasting with the broad, Polycomb-enriched domains reported for human XIST RNA. We find that Xist binding is associated with down-modulation of autosomal gene expression. However, unlike on the Xi, Xist binding does not lead to full silencing and also does not spread beyond the target gene. Over-expressing Xist in transgenic ES cells similarly leads to autosomal gene suppression, while deleting Xist ’s Repeat B motif reduces autosomal binding and perturbs autosomal down-regulation. Furthermore, treating female ES cells with the Xist inhibitor, X1, leads to loss of autosomal suppression. Altogether, our findings reveal that Xist targets ~100 genes beyond the Xi, identify Repeat B as a crucial domain for its in-trans function in mice, and indicate that autosomal targeting can be disrupted by a small molecule inhibitor.

  PublisherDOI

Recent grants

• Polycomb complexes targeted to specific loci by long noncoding RNA cofactors.

  NIH · $3.7M · 2010–2018

• Regulation of X-chromosome inactivation and imprinting by non-coding elements

  NIH · $7.1M · 1999–2026

• Regulation of X-chromosome Inactivation and Imprinting by Non-coding Elements

  NIH · $4.1M · 1999–2021

• Advancing an XIST ASO candidate for the treatment of Rett Syndrome

  NIH · $6.2M · 2019–2029

• The RNA-activation platform to treat X-linked disease in a locus-specific manner.

  NIH · $1.7M · 2013–2018

Frequent coauthors

• Yesu Jeon

  Massachusetts General Hospital

  191 shared

• Ruslan I. Sadreyev

  164 shared

• Stefan F. Pinter

  UConn Health

  158 shared

• Eda Yildirim

  Dokuz Eylül University

  140 shared

• Barry Kesner

  Massachusetts General Hospital

  116 shared

• Bernhard Payer

  Pompeu Fabra University

  109 shared

• Hongjae Sunwoo

  Massachusetts General Hospital

  88 shared

• David Colognori

  University of California, Berkeley

  86 shared

Labs

• Lee GroupPI

Awards & honors

• 2020 Justin Jankunas Doctoral Dissertation Award in American…