About

Yi-Wei Chang, Ph.D., is an Assistant Professor of Biochemistry and Biophysics at the University of Pennsylvania's Perelman School of Medicine. He serves as the Associate Director of the Institute of Structural Biology. His research expertise encompasses structural biology, cryo-electron microscopy, cryo-electron tomography, correlative light and electron microscopy, cellular imaging, microbiology, and host-pathogen interaction. Dr. Chang's work focuses on elucidating the ultrastructure and molecular mechanisms of various biological systems, including the assembly of influenza ribonucleoprotein complexes, kinetochore formation, and the ultrastructure of human brain tissue. His research also extends to studying the secretion systems of apicomplexan parasites such as Toxoplasma gondii and Plasmodium falciparum, providing insights into parasite invasion and motility. Dr. Chang's contributions to the field are recognized through multiple awards, including the Packard Fellowship in Science and Engineering and the ASPIRE Award from The Mark Foundation for Cancer Research.

Research topics

• Biology
• Chemistry
• Cell biology
• Biophysics
• Physics
• Anatomy
• Computational biology
• Biochemistry
• Materials science
• Nanotechnology
• Genetics

Selected publications

• Data from: Isoform-specific steric zippers drive aberrant assembly and mislocalization of shortened TDP-43

  DRYAD · 2026-05-02

  datasetOpen access

  TDP-43 is an essential RNA-binding protein. Cytoplasmic aggregation of TDP-43 is a hallmark of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and related neurodegenerative disorders. Shortened TDP-43 (sTDP-43) splice isoforms, which lack most of the prion-like domain (PrLD) but are enriched in motor neurons, are highly insoluble in cells and ALS patient tissue despite the near-complete absence of the PrLD. This dataset provides the quantitative data underlying experiments that define the sequence-encoded basis for aberrant sTDP-43 assembly. Data include: thioflavin T (ThT) fluorescence and turbidity kinetic measurements from in vitro aggregation and fibrillization assays; fluorescence microscopy quantification of aggregate area using CellProfiler; sedimentation (supernatant/pellet fractionation) densitometry; aggregation prevention assays with RNA and IC50 determinations; electrophoretic mobility shift assay (EMSA) quantification of RNA binding; ZipperDB fibrillization propensity scores; longitudinal neuronal survival data from rodent primary cortical neurons; and nuclear/cytoplasmic localization ratios from HEK293T cells. Proteins examined include full-length TDP-43 (flTDP-43), sTDP-43, sTDP-43ΔC-tail, steric zipper-disrupting variants (sTDP-435G, sTDP-43I281P, sTDP-43L291P, sTDP-43I281PL291P), sTDP-43_18aa, and sTDP-432P_mut_18aa.

  PublisherDOI

• BPS2026 – Elucidating the structures and functions of the Kingella kingae type IV pili-associated PilC proteins and their role in translocation across the respiratory epithelium

  Biophysical Journal · 2026-02-01

  articleSenior author
  PublisherDOI

• Two anchoring proteins control daughter apical complex assembly in <i>Toxoplasma gondii</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-14

  articleOpen access

  Abstract During Toxoplasma gondii division, the apical complex—comprising the conoid, apical polar ring (APR), and preconoidal rings—assembles with precise spatiotemporal coordination to form functional daughter buds. Despite their essential roles in invasion, motility, and division, the scaffolding proteins orchestrating this ordered assembly have remained largely unidentified. Here, we identify and characterize RCC1-2 and APR8 as essential factors directing distinct, sequential phases of daughter cell apical complex construction. Both proteins are recruited with precise spatial and temporal dynamics to the daughter buds, where they function as scaffolds rather than static structural components. APR8 transiently occupies the basal region of the APR specifically in early daughter cells. It is dispensable for conoid and PCR initiation, yet its loss causes APR collapse, abolishes SPMT anchoring, and eventually arrests conoid maturation. In contrast, RCC1-2 localizes beneath the APR basal layer and persists throughout daughter cell development, where it contributes to stabilizing the attachment of SPMTs to the APR. Notably, in situ cryo-electron tomography further reveals that the interspersed pillars bridging SPMTs ends to the APR fail to form properly in RCC1-2-depleted parasites. These findings map a hierarchical RCC1-2/APR8-dependent scaffolding process that advances our understanding of parasite replication.

  PublisherDOI

• Optimal <i>st</i>-PMMA/C₆₀ helical inclusion complexes via tunable energy landscapes for the application of an Ag SERS-active substrate

  Journal of Applied Crystallography · 2025-03-19 · 1 citations

  articleOpen access

  In bio-inspired systems, the hierarchical structures of biomolecules are mimicked to impart desired functions to self-assembled materials. However, these hierarchical architectures are based on multicomponent systems, which require not only a well defined primary structure of functional molecules but also the programming of self-assembly pathways. In this study, we investigate pathway complexity in the energy landscape of the syndiotactic poly(methyl methacrylate) ( st -PMMA)/C 60 /toluene complex system, where C 60 and toluene serve as guests in the st -PMMA helical host. Structural characterization revealed that st -PMMA preferentially wraps around C 60 , forming a thermodynamically favorable helical inclusion complex (HIC). However, during the preparation of the st -PMMA/C 60 HIC, a lengthy guest-exchange pathway was discovered, where the st -PMMA/toluene HIC transformed into the st -PMMA/C 60 HIC. This pathway complexity may hinder the formation of the st -PMMA/C 60 HIC within a feasible timeframe. Given that the energy landscape can be modulated by temperature, the st -PMMA host can directly wrap around C 60 in higher temperature ranges, thereby bypassing the guest-exchange process and increasing the st -PMMA/C 60 HIC formation efficiency. Additionally, after self-assembly programming, the st -PMMA/C 60 HIC can serve as an excellent photochemical reduction site. The well dispersed nanodomains of the st -PMMA/C 60 HICs act as nanoparticle templates for surface-enhanced Raman scattering (SERS) hotspot fabrication. We successfully utilized these HIC templates to synthesize self-assembled SERS-active silver nanoparticle arrays, demonstrating their potential for use in chemical sensing applications. In summary, a clear energy landscape can guide supramolecular engineering to achieve the desired supramolecular architectures by selecting appropriate self-assembly pathways.

  PublisherOA PDFDOI

• Droplet Squeeze Microfluidic Platform for Generating Extracellular Vesicle Hybrids for Drug Delivery

  Small · 2025-08-07 · 8 citations

  articleOpen access

  Extracellular vesicles (EVs) are emerging as versatile drug delivery systems due to their intrinsic biocompatibility and targeting capabilities. However, EV integrity and efficient drug loading challenges hinder their clinical translation. To address these limitations, hybrid systems integrating lipid nanoparticles (LNPs) with EVs have gained attention for their potential in targeted and combinatorial drug delivery. This study presents a robust microfluidic approach for the scalable generation of drug-loaded EV-LNP hybrids (EV hybrids). The method facilitates controlled fusion between EVs and LNPs by utilizing a droplet-mediated squeezing mechanism. Lipid composition and microfluidic parameters are optimized for the fusion of EVs and LNPs and determined physicochemical and functional characterizations of the EV hybrids. In vitro studies demonstrate that EV hybrids exhibit enhanced targeting efficiency. Moreover, small-molecule therapeutics are successfully encapsulated within EV hybrids, significantly improving cytotoxic efficacy against melanoma in 2D and 3D culture models compared to drug-loaded EVs or LNPs alone. The work introduces a scalable, minimally disruptive microfluidic platform for engineering EV hybrids, offering a promising strategy to advance precision nanomedicine.

  PublisherOA PDFDOI

• PilY proteins: bimodular drivers of type IV pilus versatility

  Trends in Microbiology · 2025-11-26 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• Author response: Inflammasomes primarily restrict cytosolic Salmonella replication within human macrophages

  2025-03-27

  peer-reviewOpen access
  PublisherDOI

• Space tourism marketing management considerations: locating in tourism spectrums, measuring motivated consumer innovativeness via moderating role of perceived risks, and challenging in environment

  Acta Astronautica · 2025-06-13 · 3 citations

  article1st authorCorresponding
  PublisherDOI

• Repositioning of polyubiquitin alters the pathologic tau filament structure

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-08

  preprintOpen access

  Abstract Structurally diverse tau filaments form proteinaceous aggregates in a heterogeneous group of neurodegenerative diseases called tauopathies 1 . The factors extrinsic to the highly ordered core structure that influence tau filament stability are not well understood. Here, we found that polyubiquitinated tau filaments from Alzheimer’s disease and vacuolar tauopathy human brain tissue exhibit distinct seeding patterns in mice, in association with differences in tau filament ultrastructure determined by cryo-electron microscopy. Interestingly, chemical modulation of the polarity of polyubiquitin adjacent to the tau core with the small molecule ubistatin B resulted in the repositioning of poorly structured densities towards positively charged residues on the highly structured core filament, leading to shifting of the protofilament-protofilament interface of certain vacuolar tauopathy tau filaments. These results suggest that the structure of tau filaments that are associated with different seeding activities in vivo can be influenced by post-translational modifications.

  PublisherOA PDFDOI

• Molecular basis of influenza ribonucleoprotein complex assembly and processive RNA synthesis

  Science · 2025-05-15 · 17 citations

  articleOpen accessSenior authorCorresponding

  Influenza viruses replicate and transcribe their genome in the context of a conserved ribonucleoprotein (RNP) complex. By integrating cryo-electron microscopy single-particle analysis and cryo-electron tomography, we define the influenza RNP as a right-handed, antiparallel double helix with the viral RNA encapsidated in the minor groove. Individual nucleoprotein subunits are connected by a flexible tail loop that inserts into a conserved pocket in its neighbor. We visualize the viral polymerase in RNP at different functional states, revealing how it accesses the RNA template while maintaining the double-helical architecture of RNP by strand sliding. Targeting the tail loop binding interface, we identify lead compounds as potential anti-influenza inhibitors. These findings elucidate the molecular determinants underpinning influenza virus replication and highlight a promising target for antiviral development.

  PublisherOA PDFDOI

Frequent coauthors

• Grant J. Jensen

  Brigham Young University

  88 shared

• Catherine M. Oikonomou

  California Institute of Technology

  22 shared

• Debnath Ghosal

  University of Melbourne

  19 shared

• Mohammed Kaplan

  19 shared

• Shrawan Kumar Mageswaran

  University of Pennsylvania

  18 shared

• Chwan‐Deng Hsiao

  Institute of Molecular Biology, Academia Sinica

  16 shared

• Morgan Beeby

  15 shared

• Ariane Briegel

  Leiden University

  13 shared

Education

• Ph.D., Bioinformatics and Structural Biology

  National Tsing Hua University

  2010

• B.S., Mechanical Engineering

  Chung Hua University

  2004

Awards & honors

• 2022 FIB-Milling Sample Preparation for Cellular CryoET Awar…
• 2019 ASPIRE Award, The Mark Foundation for Cancer Research
• 2022 Catalysts Fellow, The EMBO Journal
• 2019 Packard Fellowships in Science and Engineering, The Dav…
• 2025 Michael S. Brown New Investigator Research Award