About

Erfei Bi, Ph.D., is a Professor of Cell and Developmental Biology at the University of Pennsylvania's Perelman School of Medicine. His research focuses on elucidating the molecular mechanisms of cytokinesis and septin assembly and function, utilizing both yeast and mammalian cells as model systems through an integrative approach involving genetics, advanced imaging, and biochemistry. His laboratory's work centers on dissecting the architecture and regulation of the actomyosin ring, mechanisms of targeted vesicle fusion, and ECM remodeling during cell division. Additionally, his research investigates how cytokinesis is linked to hepatocyte polarization and bile canaliculus formation, which are essential to liver architecture and function. Dr. Bi's contributions include uncovering the regulation of septin assembly, the roles of non-muscle myosin-II isoforms in cytokinesis, and the molecular pathways governing cell division and polarization.

Research topics

• Biology
• Cell biology
• Genetics
• Chemistry
• Computational biology

Selected publications

• efsrf

  2026-03-06

  reportOpen access1st authorCorresponding
  PublisherOA PDFDOI

• E- and N-cadherin drive hepatic polarity and lumen elongation via opposing effects on RhoA activity

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-06

  preprintOpen accessSenior authorCorresponding

  Abstract Hepatocytes exhibit distinct polarity, forming narrow apical tubes (bile canaliculi, BCs) between adjacent cells. These structures essential to liver architecture and function. Unlike most epithelial cells, hepatocytes express both E- and N-cadherin but their functions and mechanisms remain unknown. We show that E- and N-cadherin are collectively required for hepatic polarity and BC formation but act through distinct, spatially segregated pathways. Both localize to adherens junctions; E-cadherin additionally localizes to lateral membranes and the cleavage furrow during cell division, where it promotes BC elongation and new cell-cell contact formation by controlling spindle orientation and RhoA activation via NuMA and ARHGEF17. N-cadherin maintains hepatic polarity by facilitating RhoA inactivation through the p120-catenin family member ARVCF and its partner p190B/ARHGAP5. Thus, dual cadherin expression drives hepatic polarity and BC formation by controlling RhoA activity in a coordinated but opposing manner. Summary Hayase et al. show that E-cadherin promotes bile canaliculi elongation via RhoA activation and oriented cell division, while N-cadherin maintains hepatic polarity by suppressing RhoA, revealing the function and mechanism of dual cadherin expression in hepatocytes.

  PublisherOA PDFDOI

• Bni5 regulates and coordinates septin architecture and myosin-II functions at the cell division site

  The Journal of Cell Biology · 2025-11-06

  articleOpen accessSenior author

  The spatiotemporal coordination of septins and myosin-II in processes like cytokinesis is not well understood. In Saccharomyces cerevisiae, Bni5 links the myosin-II heavy chain Myo1 to the septin hourglass at the bud neck prior to cytokinesis, but the underlying mechanisms and functions remain unclear. Here, we show that Bni5 binds septin filaments, the septin-associated kinase Elm1, and Myo1 via distinct domains. Bni5 regulates the architecture and stability of the septin hourglass until it dissociates from the bud neck at the onset of cytokinesis. This dissociation, facilitated through phosphorylation of Bni5 by Gin4, an Elm1-interacting kinase, enables timely remodeling of the septin hourglass into a double ring. Bni5 also mediates the role of Myo1 in retrograde actin cable flow during polarized growth and ensures maximal accumulation of Myo1 at the bud neck before cytokinesis, reinforcing the actomyosin ring and buffering it against perturbations. These findings establish Bni5 as a key regulator and coordinator of septins and myosin-II at the division site.

  PublisherDOI

• Reciprocal regulation by Elm1 and Gin4 controls septin hourglass assembly and remodeling

  The Journal of Cell Biology · 2024-03-05 · 11 citations

  articleOpen accessSenior authorCorresponding

  The septin cytoskeleton is extensively regulated by posttranslational modifications, such as phosphorylation, to achieve the diversity of architectures including rings, hourglasses, and gauzes. While many of the phosphorylation events of septins have been extensively studied in the budding yeast Saccharomyces cerevisiae, the regulation of the kinases involved remains poorly understood. Here, we show that two septin-associated kinases, the LKB1/PAR-4-related kinase Elm1 and the Nim1/PAR-1-related kinase Gin4, regulate each other at two discrete points of the cell cycle. During bud emergence, Gin4 targets Elm1 to the bud neck via direct binding and phosphorylation to control septin hourglass assembly and stability. During mitosis, Elm1 maintains Gin4 localization via direct binding and phosphorylation to enable timely remodeling of the septin hourglass into a double ring. This mutual control between Gin4 and Elm1 ensures that septin architecture is assembled and remodeled in a temporally controlled manner to perform distinct functions during the cell cycle.

  PublisherOA PDFDOI

• ASpdb: an integrative knowledgebase of human protein isoforms from experimental and AI-predicted structures

  Nucleic Acids Research · 2024-11-12 · 8 citations

  articleOpen access

  Alternative splicing is a crucial cellular process in eukaryotes, enabling the generation of multiple protein isoforms with diverse functions from a single gene. To better understand the impact of alternative splicing on protein structures, protein-protein interaction and human diseases, we developed ASpdb (https://biodataai.uth.edu/ASpdb/), a comprehensive database integrating experimentally determined structures and AlphaFold 2-predicted models for human protein isoforms. ASpdb includes over 3400 canonical isoforms, each represented by both experimentally resolved and predicted structures, and >7200 alternative isoforms with AlphaFold 2 predictions. In addition to detailed splicing events, 3D structures, sequence variations and functional annotations, ASpdb uniquely offers comparative analyses and visualization of structural alterations among isoforms. This resource is invaluable for advancing research in alternative splicing, structural biology and disease mechanisms.

  PublisherDOI

• Systematic characterization of protein structural features of alternative splicing isoforms using AlphaFold 2

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-02-01 · 1 citations

  preprintOpen access

  Alternative splicing is an important cellular process in eukaryotes, altering pre-mRNA to yield multiple protein isoforms from a single gene. However, our understanding of the impact of alternative splicing events on protein structures is currently constrained by a lack of sufficient protein structural data. To address this limitation, we employed AlphaFold 2, a cutting-edge protein structure prediction tool, to conduct a comprehensive analysis of alternative splicing for approximately 3,000 human genes, providing valuable insights into its impact on the protein structural. Our investigation employed state of the art high-performance computing infrastructure to systematically characterize structural features in alternatively spliced regions and identified changes in protein structure following alternative splicing events. Notably, we found that alternative splicing tends to alter the structure of residues primarily located in coils and beta-sheets. Our research highlighted a significant enrichment of loops and highly exposed residues within human alternatively spliced regions. Specifically, our examination of the Septin-9 protein revealed potential associations between loops and alternative splicing, providing insights into its evolutionary role. Furthermore, our analysis uncovered two missense mutations in the Tau protein that could influence alternative splicing, potentially contributing to the pathogenesis of Alzheimer's disease. In summary, our work, through a thorough statistical analysis of extensive protein structural data, sheds new light on the intricate relationship between alternative splicing, evolution, and human disease.

  PublisherOA PDFDOI

• Elucidating the Synergistic Role of Elm1 and Gin4 Kinases in Regulating Septin Hourglass Assembly

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-11-08 · 1 citations

  preprintOpen accessSenior authorCorresponding

  ABSTRACT The septin cytoskeleton is extensively regulated by post-translational modifications such as phosphorylation to achieve the diversity of architectures including rings, hourglass, and gauzes. While many of the phosphorylation events of septins have been extensively studied in the budding yeast Saccharomyces cerevisiae , the regulation of the kinases involved remains poorly understood. Here we show that two septin-associated kinases, the LKB1/PAR-4-related kinase Elm1 and the Nim1/PAR-1-related kinase Gin4, regulate each other at two discrete points of the cell cycle. During bud emergence, Gin4 targets Elm1 to the bud neck via direct binding and phosphorylation to control septin hourglass assembly and stability. During mitosis, Elm1 maintains Gin4 localization via direct binding and phosphorylation to enable timely remodeling of the septin hourglass into a double ring. This unique synergy ensures that septin architecture is assembled and remodeled in a temporally controlled manner to perform distinct functions during the cell cycle. SUMMARY Marquardt et al. show that the septin-associated kinases Elm1 and Gin4 regulate each other via both direct binding and phosphorylation to control septin hourglass assembly and remodeling at different points of the cell cycle in the budding yeast Saccharomyces cerevisiae .

  PublisherOA PDFDOI

• Bni5 tethers myosin-II to septins to enhance retrograde actin flow and the robustness of cytokinesis

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-11-08 · 5 citations

  preprintOpen accessSenior authorCorresponding

  Abstract The collaboration between septins and myosin-II in driving processes outside of cytokinesis remains largely uncharted. Here, we demonstrate that Bni5 in the budding yeast S. cerevisiae interacts with myosin-II, septin filaments, and the septin-associated kinase Elm1 via distinct domains at its N- and C-termini, thereby tethering the mobile myosin-II to the stable septin hourglass at the division site from bud emergence to the onset of cytokinesis. The septin and Elm1-binding domains, together with a central disordered region, of Bni5 control timely remodeling of the septin hourglass into a double ring, enabling the actomyosin ring constriction. The Bni5-tethered myosin-II enhances retrograde actin cable flow, which contributes to the asymmetric inheritance of mitochondria-associated protein aggregates during cell division, and also strengthens cytokinesis against various perturbations. Thus, we have established a biochemical pathway involving septin-Bni5-myosin-II interactions at the division site, which can inform mechanistic understanding of the role of myosin-II in other retrograde flow systems. Summary Okada et al. have determined the molecular mechanism underlying the Bni5 interactions with septins and myosin-II at the cell division site and uncovered its roles in promoting retrograde actin flow and the robustness of cytokinesis in budding yeast.

  PublisherOA PDFDOI

• Unraveling the mechanisms and evolution of a two-domain module in IQGAP proteins for controlling eukaryotic cytokinesis

  Cell Reports · 2023-11-30 · 8 citations

  articleOpen accessSenior authorCorresponding

  The IQGAP family of proteins plays a crucial role in cytokinesis across diverse organisms, but the underlying mechanisms are not fully understood. In this study, we demonstrate that IQGAPs in budding yeast, fission yeast, and human cells use a two-domain module to regulate their localization as well as the assembly and disassembly of the actomyosin ring during cytokinesis. Strikingly, the calponin homology domains (CHDs) in these IQGAPs bind to distinct cellular F-actin structures with varying specificity, whereas the non-conserved domains immediately downstream of the CHDs in these IQGAPs all target the division site, but differ in timing, localization strength, and binding partners. We also demonstrate that human IQGAP3 acts in parallel to septins and myosin-IIs to mediate the role of anillin in cytokinesis. Collectively, our findings highlight the two-domain mechanism by which IQGAPs regulate cytokinesis in distantly related organisms as well as their evolutionary conservation and divergence.

  PublisherOA PDFDOI

• Unravelling the Mechanisms and Evolution of a Two-Domain Module in Iqgap Proteins for Controlling Eukaryotic Cytokinesis

  SSRN Electronic Journal · 2023-01-01 · 1 citations

  preprintOpen accessSenior author
  PublisherDOI

Recent grants

• NIH Grant R01GM087365

  NIH · $1.2M · 2015

• Mechanistic Analysis of Cytokinesis in Eukaryotes

  NIH · $3.7M · 2015–2024

• Analysis of Septin Structure and Function

  NIH · $3.4M · 2016–2024

• NIH Grant R01GM059216

  NIH · $4.0M · 2013

Frequent coauthors

• John R. Pringle

  Stanford University

  38 shared

• Carsten Wloka

  Freie Universität Berlin

  29 shared

• Hiroki Okada

  Kirin (United States)

  13 shared

• Daniel J. Lew

  Duke University

  12 shared

• Satoshi Okada

  Kyushu University

  12 shared

• Claudio De Virgilio

  University of Fribourg

  11 shared

• Kathleen Corrado

  11 shared

• John N. McMillan

  10 shared

Labs

• Cell and Developmental BiologyPI