About

Megan C. King, PhD, is a Professor of Cell Biology and of Molecular, Cellular and Development Biology at Yale School of Medicine. She received her B.A. in Biochemistry from Brandeis University, her Ph.D. in Biochemistry and Molecular Biophysics from the University of Pennsylvania, and completed postdoctoral training with Dr. Günter Blobel at Rockefeller University. Her research focuses on the biological functions integrated at the nuclear envelope, including impacts on DNA repair and nuclear and cellular mechanics. She investigates mechanisms such as macromolecular complexes embedded in the nuclear envelope that couple the cytoskeleton to the nucleus, aiming to define the fundamental mechanisms underlying nuclear force response and force transduction to the nuclear lamina, using models like fission yeast, cell culture, and mice. Additionally, her work involves defining how the genome is organized, leveraging insights from chromatin dynamics, and studying how nuclear cell biology influences genome integrity.

Research topics

• Biology
• Cell biology
• Genetics
• Chemistry
• Cancer research
• Biochemistry
• Psychology
• Oncology
• Internal medicine
• Medicine

Selected publications

• Sense, plug, and seal: proteins as both rapid responders and constitutive barriers supporting organelle compartmentalization

  Molecular Biology of the Cell · 2025-07-02 · 6 citations

  review1st authorCorresponding

  Although organellar compartmentalization is primarily established by the delimiting phospholipid bilayer membranes, the contribution of proteins has been less appreciated. Recently, studies across many realms of cell biology have put new focus on the role of proteins in acting as diffusion barriers in contexts where there are constitutive, regulated, or pathological discontinuities in membranes. Here, we synthesize longstanding observations of proteins acting as both barriers to lateral diffusion on membranes and diffusion in three-dimensional space. In particular, we focus on an emerging, conserved two-step paradigm of protein diffusion barriers that rapidly assemble in response to membranous organelle damage: a first phase of coincident sensing and stopgap "plugging" by responding repair proteins followed by a second phase of membrane sealing. We highlight recent work exemplifying this sense, plug, and seal paradigm at the postmitotic nuclear envelope and at ruptures of the interphase nuclear envelope, lysosomes, and the plasma membrane. Taken together, we highlight how cells use a variety of constitutive and induced proteinaceous barriers that support the role of biological membranes in defining organelle compartmentalization. Determining the biophysical nature of these barriers, and their means of "sensing" membrane rupture, will be an exciting avenue of future investigations.

  PublisherDOI

• eLife Assessment: An Hfq-dependent post-transcriptional mechanism fine tunes RecB expression in Escherichia coli

  2025-08-12

  peer-reviewOpen access1st authorCorresponding

  Single-molecule mRNA and protein quantification, combined with stochastic modelling, uncover a post-transcriptional regulatory mechanism that controls the expression of the extremely low-abundance DNA double-strand break repair enzyme RecBCD.

  PublisherDOI

• Nuclear mechanics as a determinant of nuclear pore complex plasticity

  Nature Cell Biology · 2025-09-19 · 8 citations

  articleSenior author
  PublisherDOI

• eLife Assessment: Treacle’s ability to form liquid-like phase condensates is essential for nucleolar fibrillar center assembly, efficient rRNA transcription and processing, and rRNA gene repair

  2025-04-14

  peer-reviewOpen access1st authorCorresponding

  Treacle condensation, driven by alternating charge blocks, facilitates interactions with transcription factors to spatially segregate ribosomal RNA synthesis and processing, while also recruiting TOPBP1 for activation of the rDNA damage response.

  PublisherDOI

• Coarse-grained chromatin dynamics by tracking multiple similarly labeled gene loci

  Biophysical Journal · 2025-05-13

  article
  PublisherDOI

• Coarse-grained chromatin dynamics by tracking multiple similarly labeled gene loci

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-02

  preprintOpen access

  ABSTRACT The “holy grail” of chromatin research would be to follow the chromatin configuration in individual live cells over time. One way to achieve this goal would be to track the positions of multiple loci arranged along the chromatin polymer with fluorescent labels. Use of distinguishable labels would define each locus uniquely in a microscopic image but would restrict the number of loci that could be observed simultaneously, because of experimental limits to the number of distinguishable labels. Use of the same label for all loci circumvents this limitation but requires a (currently lacking) framework for how to establish each observed locus identity, i.e. to which genomic position it corresponds. Here we analyze theoretically, using simulations of Rouse-model polymers, how single-particle-tracking of multiple identically-labeled loci enables determination of loci identity. We show that the probability of correctly assigning observed loci to genomic positions converges exponentially to unity as the number of observed loci configurations increases. The convergence rate depends only weakly on the number of labeled loci, so that even large numbers of loci can be identified with high fidelity by tracking them across about 8 independent chromatin configurations. In the case of two distinct labels that alternate along the chromatin polymer, we find that the probability of the correct assignment converges faster than for same-labeled loci, requiring observation of fewer independent chromatin configurations to establish loci identities. Finally, for a modified Rouse-model polymer, that realizes a population of dynamic loops, we find that the success probability also converges to unity exponentially as the number of observed loci configurations increases, albeit slightly more slowly than for a classical Rouse model polymer. Altogether, these results establish particle tracking of multiple identically- or alternately-labeled loci over time as a feasible way to infer temporal dynamics of the coarse-grained configuration of the chromatin polymer in individual living cells. SIGNIFICANCE In spite of recent success in elucidating its spatial organization, chromatin’s time-dependent, dynamical behavior remains far less studied, and correspondingly much less understood. To address the critical need to elucidate chromatin dynamics, this paper proffers a route towards an experimental characterization of coarse-grained chromosomal dynamics, via particle tracking of multiple labeled loci, labeled with just one or two different fluophor colors or intensities. Theoretically, we show that particle tracking of multiple identically labeled loci across only about 8 independent chromatin configurations should be a feasible way to establish the time-dependent, coarse-grained configuration of the chromatin polymer in individual living cells.

  PublisherOA PDFDOI

• eLife Assessment: Treacle’s ability to form liquid-like phase condensates is essential for nucleolar fibrillar center assembly, efficient rRNA transcription and processing, and rRNA gene repair

  2025-03-31

  peer-reviewOpen access1st authorCorresponding

  We investigated the role of the nucleolar protein Treacle in organizing and regulating the nucleolus in human cells. Our results support Treacle’s ability to form liquid-like phase condensates through electrostatic interactions among molecules. The formation of these biomolecular condensates is crucial for segregating nucleolar fibrillar centers from the dense fibrillar component and ensuring high levels of rRNA gene transcription and accurate rRNA processing. Both the central and C-terminal domains of Treacle are required to form liquid-like condensates. The initiation of phase separation is attributed to the C-terminal domain. The central domain is characterized by repeated stretches of alternatively charged amino-acid residues and is vital for condensate stability. Overexpression of mutant forms of Treacle that cannot form liquid-like phase condensates compromises the assembly of fibrillar centers, suppressing rRNA gene transcription and disrupting rRNA processing. These mutant forms also fail to recruit DNA topoisomerase II binding protein 1 (TOPBP1), suppressing the DNA damage response in the nucleolus.

  PublisherDOI

• Presence 5 for trauma informed care: teaching tangible practices towards bidirectional healing in undergraduate medical education

  BMC Medical Education · 2025-12-05

  articleOpen access1st authorCorresponding

  INTRODUCTION: Trauma impacts health; the adverse health effects of trauma are well-understood and trauma-informed care is recommended to mitigate these effects. There is an opportunity to leverage evidence-based frameworks to add to the growing body of literature on teaching trauma-informed care within undergraduate medical education. To address this, we developed, implemented, and evaluated the Presence 5 for Trauma Informed Care Workshop (P5 TIC), a discussion-based workshop, informed by evidence and guided by a clinical case, to teach tangible trauma-informed care practices in undergraduate medical education. METHODS: P5 TIC was developed by abstracting practices from a narrative literature review and mapping them to the Presence 5 framework. Evidence-based practices informed the development of a 1-hour, in-person workshop comprising didactics followed by a case-based discussion. P5 TIC was implemented with undergraduate medical students (n = 144) through the Practice of Medicine Course. Participants completed a pre- and post-workshop survey to evaluate confidence and attitudes related to trauma informed care. RESULTS: Literature review resulted in the following P5 TIC practices: (1) Prepare with Intention (e.g., chart review mindfully) (2), Listen Intently and Completely (e.g., listen for signs and impacts of trauma when your patient is ready to share) (3) , Agree on What Matters Most (e.g., prioritize your patient's trauma-related medical needs) (4), Connect with the Patient's Story (e.g., reflect on how trauma intersects with healthcare) (5), Explore Emotional Cues (e.g., tune into body language and non-verbal cues), and (6)Care for Yourself (e.g., practice compassionate detachment). Learner confidence and attitudes related to trauma informed care increased after participation in P5 TIC. CONCLUSION: P5 TIC is a structured, evidence-based approach to teaching trauma informed care and adds to the literature in providing tangible practices as well as addressing self-care. Further medical education research should be conducted to explore the impact of P5 TIC on learner and patient outcomes.

  PublisherDOI

• Contemporary Dissemination Rates Among Research Presented at Obstetrics and Gynecology Subspecialty Conferences

  O&G Open · 2025-09-18 · 1 citations

  articleOpen access

  OBJECTIVE: We aimed to evaluate the conversion rate of conference abstract presentation to full manuscript among obstetrics and gynecology subspecialty society meetings. METHODS: We conducted a retrospective cohort study of 2019 meeting supplements from four subspecialty societies: 1) the American Society for Reproductive Medicine (ASRM), 2) the American Urogynecologic Society (AUGS), 3) the Society of Gynecologic Oncology (SGO), and 4) the Society for Maternal-Fetal Medicine (SMFM). All abstracts that were not subsequently withdrawn were included and queried on PubMed using a multimodal method that incorporated abstract keywords and the names of the first and last author to determine publication status. An abstract was classified as a published manuscript if the first author of the meeting abstract was credited in the final publication. The primary outcome was overall publication status. Secondary outcomes included subdivided oral and poster abstract publication conversion, publication journal type, manuscript journal impact factor, time to publication, and additional presentation metrics. RESULTS: Among the 3,425 total conference abstracts presented in 2019, the overall oral and poster abstract publication rate for all societies combined was 39.7% (subspecialty range, 33.1–47.5%). For only oral abstracts, 61.0% (subspecialty range, 50.7–78.6%) were published and, for only poster abstracts, 35.4% (subspecialty range 27.1–45.4%) were published. When comparing among subspecialty societies, there were significant differences in rates of oral abstract conversion, with ASRM at 50.7%, AUGS at 64.9%, SGO at 78.6%, and SMFM at 74.5% ( P <.01), and in rates of poster abstract conversion, with ASRM at 27.1%, AUGS at 27.3%, SGO at 45.4%, and SMFM at 40.5% ( P <.01). Most of the dissemination occurred in general obstetrics and gynecology journals and not in the society associated journals. The median (interquartile range) journal impact factor was 4.7 (2.1, 7.2) among oral abstracts and 3.3 (2.1, 4.8) among poster abstracts ( P <.01). The median (interquartile range) time to publication was 16 months (9, 26 months) among oral abstracts and 17 months (9, 30 months) among poster abstracts ( P =.13). CONCLUSION: Our contemporary evaluation of women's health research dissemination shows that a significant portion of research presented at obstetrics and gynecology subspecialty conferences remains unpublished, even after 5 years.

  PublisherDOI

• The LINC complex component Kms1 and CENP-B protein Cbp1 cooperate to enforce faithful homology-directed DNA repair at the nuclear periphery in <i>S. pombe</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-18

  preprintOpen accessSenior authorCorresponding

  Abstract While homologous recombination (HR) is often considered to be an error-free DNA repair mechanism, the fidelity of this pathway depends on the cell’s ability to engage the ideal template, the replicated sister chromatid. This is particularly challenging during repair of repetitive genome regions for which non-allelic sequences can errantly be used as templates. Here, we develop a model to study spontaneous DNA damage and repair that occurs at repetitive protein coding genes of the S. pombe flocculin family. We observe that genes encoding most members of this protein family constitutively reside at the nuclear periphery by virtue of their close proximity to binding sites for the CENP-B like protein, Cbp1. Tethering via Cbp1 to the nuclear periphery enhances the stability of the flocculin genes against intragenic recombination and restrains intergenic recombination between homoeologous repeat-encoding sequences. The LINC complex component Kms1 also antagonizes both intragenic and intergenic recombination at the flocculin genes as well as microhomology-mediated end-joining (MMEJ). Our observations suggest that S. pombe leverages nuclear compartmentalization to maintain the stability of repetitive genic regions at the nuclear periphery while association of DSBs with Kms1-containing LINC complexes enforces stringency to avoid mutagenic end-joining and use of the incorrect template during HR.

  PublisherOA PDFDOI

Recent grants

• Leveraging cancer-specific defects in nuclear integrity to inform novel synthetic lethal strategies

  NIH · $401k · 2019–2021

• EFRI CEE: Sculpting the genome by design: epigenetic and chromatin looping inputs to measure and manipulate chromatin organization and dynamics

  NSF · $2.2M · 2018–2024

• NIH Grant F32GM077919

  NIH · $62k · 2008

• Remodeling of the structure and function of the nuclear lamina by LINC complex-dependent tension

  NIH · $1.3M · 2018–2023

• NIH Grant R21HG006742

  NIH · $458k · 2015

Frequent coauthors

• C. Patrick Lusk

  Yale University

  21 shared

• S. G. J. Mochrie

  Yale University

  20 shared

• Ivan V. Surovtsev

  Yale University

  15 shared

• Jessica F. Williams

  Yale University

  14 shared

• Günter Blobel

  Howard Hughes Medical Institute

  12 shared

• Mark A. Lemmon

  Yale University

  10 shared

• Bryan A. Leland

  Yale University

  10 shared

• Angela Pickart

  Mayo Clinic

  10 shared

Labs

• LusKing LabPI

Education

• B.A., Biochemistry

  Brandeis University

• Ph.D., Biochemistry and Molecular Biophysics

  Yale School of Medicine

Awards & honors

• Searle Scholar (2011)
• NIH New Innovator Award
• Allen Distinguished Investigator