A Trypanosoma cruzi Trans-Sialidase Peptide Demonstrates High Serological Prevalence Among Infected Populations Across Endemic Regions of Latin America (Preprint) Icon
February 21, 2025

Accurate diagnosis of chronic Chagas disease remains challenging due to limited sensitivity of existing serological tests. This study performed proteome-wide screening of T. cruzi and identified a novel trans-sialidase epitope (TS-2.23) with strong diagnostic potential across diverse geographic regions. Our group contributed by producing and validating candidate peptides for serological assay development.

The Interplay of Furin Cleavage and D614G in Modulating SARS-CoV-2 Spike Protein Dynamics (Preprint) Icon
January 28, 2025

Measuring conformational dynamics of the SARS-CoV-2 Spike protein in a native-like membrane environment is key to improving vaccines and therapeutics. This study used HDX-MS on enveloped virus-like particles (eVLPs) to reveal that all spike variants sampled an open-interface trimer conformation, while the D614G mutation favored a more stable closed conformation that may enhance viral fitness. Our group contributed by producing and characterizing spike proteins for HDX-MS analysis.

The Virtual Lab: AI Agents Design New SARS-CoV-2 Nanobodies with Experimental Validation (Preprint) Icon
November 12, 2024

Interdisciplinary collaboration is essential for scientific discovery, but access to diverse expertise can be limited. This study presents the “Virtual Lab,” an AI-human framework that designed 92 novel nanobody binders, two of which showed enhanced binding to SARS-CoV-2 variants. Our group helped shape the experimental design to align with our lab’s capabilities and validated the resulting nanobodies across multiple viral variants.

High-yield production of recombinant human myelin oligodendrocyte glycoprotein in SHuffle bacteria without a refolding step (Journal of Immunological Methods) Icon
November 1, 2024

This study presents a simplified method to produce human myelin oligodendrocyte glycoprotein (rhMOG) in bacteria at high yields, without complex refolding from inclusion bodies. Biochemical and biophysical data show that soluble rhMOG is stabilized by an intramolecular disulfide bond formed in the bacterial cytosol.

Open-source milligram-scale, four channel, automated protein purification system (PLOS One) Icon
February 23, 2024

Parallel purification of multiple proteins could accelerate discovery if made as robust as traditional single-protein workflows. In this study, led by the Biohub SF Bioengineering team, we developed a four-channel automated chromatography system for milligram-scale protein purification. Using it, we purified trimeric Spike proteins from several coronaviruses and monoclonal antibodies, and shared open-source hardware and software to enable others to build their own systems.

MultiSero: An Open-Source Multiplex-ELISA Platform for Measuring Antibody Responses to Infection (Pathogens) Icon
May 2, 2023

Serology is key for understanding antibody responses to SARS-CoV-2 infection and vaccination. In this collaborative study, we developed an open-source platform for multiplex serology imaging and analysis using a 96-well ELISA format. Our tools offer performance comparable to commercial systems, making high-content serosurveillance more accessible.

Efficient evolution of human antibodies from general protein language models (Nature Biotechnology) Icon
April 24, 2023

This study developed a language model–guided approach to affinity maturation, improving binding of seven antibodies by screening 20 or fewer variants — without using target antigen information. Our group contributed by generating and purifying the recombinant antibodies at high throughput.

CAR-T Cell–Mediated B-Cell Depletion in Central Nervous System Autoimmunity (Neurology Neuroimmunology & Neuroinflammation) Icon
January 3, 2023

Anti-CD20 monoclonal antibodies are effective for treating relapsing MS, but CAR-T cells may offer added benefits by targeting B cells within the CNS. This study showed that anti-CD19 CAR-T cells reduced disease in a mouse model of MS. Our group produced recombinant myelin oligodendrocyte glycoprotein used to induce EAE in mice.

SARS-CoV-2 Spike triggers barrier dysfunction and vascular leak via integrins and TGF-β signaling (Nature Communications) Icon
December 9, 2022

Severe COVID-19 involves barrier dysfunction in the lungs and other organs. This study showed that the SARS-CoV-2 Spike protein alone can trigger this dysfunction in vitro and cause vascular leak in vivo. Our group produced and characterized Spike and RBD antigens for these analyses

AIRRscape: An interactive tool for exploring B-cell receptor repertoires and antibody responses (PLOS Computational Biology) Icon
September 20, 2022

The complexity of B cell antibody repertoires makes it challenging to identify shared immune responses. In collaboration with the Biohub Data Science platform, we developed AIRRscape, an interactive R Shiny web app for exploring BCR and antibody features across multiple repertoires.

Converting non-neutralizing SARS-CoV-2 antibodies into broad-spectrum inhibitors (Nature Chemical Biology) Icon
September 8, 2022

Spike mutations in SARS-CoV-2 can reduce the effectiveness of antibody therapies. This study developed broad-spectrum inhibitors by tethering ACE2 to non-neutralizing antibodies targeting conserved Spike epitopes. Our group performed phylogenetic analyses to identify antibody candidates for ACE2 tethering.

A Single-Component Luminescent Biosensor for the SARS-CoV-2 Spike Protein (Journal of the American Chemical Society) Icon
August 3, 2022

Protein detection often relies on complex antibody reagents. This study describes a single-component luminescent biosensor expressible in E. coli and S. cerevisiae. Our group produced SARS-CoV-2 Spike and RBD proteins to test the assay’s performance.

The SARS-CoV-2 spike reversibly samples an open-trimer conformation exposing novel epitopes (Nature Structural & Molecular Biology) Icon
March 29, 2022

COVID-19 vaccines and diagnostics rely on the structure of the SARS-CoV-2 Spike ectodomain. This study used hydrogen-deuterium exchange mass spectrometry to identify a previously unobserved open-trimer conformation. Our group produced and biophysically characterized Spike protein under various conditions.

SARS-CoV-2 antibody magnitude and detectability are driven by disease severity, timing, and assay (Science Advances) Icon
July 21, 2021

Serosurveillance studies are limited by unclear antibody assay performance over time and across clinical presentations. This study tracked antibody responses in 128 individuals over 160 days using 14 assays. Our group provided Spike and Nucleocapsid proteins for the serology tests.

Citywide serosurveillance of the initial SARS-CoV-2 outbreak in San Francisco using electronic health records  (Nature Communications) Icon
June 11, 2021

Serosurveillance helps estimate population-level exposure to pathogens. This study tested remnant blood samples from San Francisco hospitals for SARS-CoV-2 antibodies. Our group contributed by producing Spike and Nucleocapsid proteins for the serology assays.

Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms (Cell Reports Medicine) Icon
May 18, 2021

Neurological symptoms are common in COVID-19, but their cause remains unclear. This study found CNS-specific T and B cell responses in affected individuals. Our group measured the binding kinetics and affinity of cerebrospinal fluid-derived antibodies to SARS-CoV-2 Spike.

Performance characteristics of a rapid severe acute respiratory syndrome coronavirus 2 antigen detection assay at a public plaza testing site in San Francisco (Journal of Infectious Diseases) Icon
April 8, 2021

The Abbott BinaxNOW rapid test detects SARS-CoV-2 N protein from nasal swabs. This study evaluated its performance in a community screening setting. Our group contributed by producing N protein to assess lot-to-lot variability in test detection.

Rapid SARS-CoV-2 spike protein detection by carbon nanotube-based near-infrared nano (Nano Letters) Icon
February 26, 2021

Rapid, accessible diagnostics are essential for detecting active SARS-CoV-2 infections. This study used ACE2-functionalized carbon nanotubes as nanosensors to detect Spike protein. Our group contributed by producing Spike protein to test sensor sensitivity.

A Single Immunization with Spike-Functionalized Ferritin Vaccines Elicits Neutralizing Antibody Responses against SARS-CoV-2 in Mice (ACS Central Science) Icon
January 5, 2021

Protein subunit vaccines offer a safe, scalable, and accessible option for SARS-CoV-2. This study showed that ferritin nanoparticles displaying truncated Spike protein elicited stronger neutralizing responses than Spike or RBD alone. Our group helped characterize the homogeneity and oligomeric state of these nanoparticles.

Identification of a Polymorphism in the N Gene of SARS-CoV-2 That Adversely Impacts Detection by Reverse Transcription-PCR (Journal of Clinical Microbiology) Icon
December 17, 2020

 In July 2020, the Biohub’s COVID-19 diagnostic lab identified over 40 samples from Madera County, California with poor N-gene assay performance due to a genetic polymorphism. Our group mapped this change onto the N protein structure to assess its impact and showed, in unpublished work, that the mutant protein was biophysically similar to wild type.

Convergent antibody responses to SARS-CoV-2 in convalescent individuals (Nature) Icon
August 5, 2020

At the start of the COVID-19 pandemic, little was known about antibody responses to SARS-CoV-2. This study showed that all 149 convalescent individuals developed potent neutralizing antibodies, supporting vaccine development. Our group contributed by designing biotinylated Spike and RBD antigens to isolate antigen-specific B cells.

Genomic and serologic characterization of enterovirus A71 brainstem encephalitis (Neurology Neuroimmunology & Neuroinflammation) Icon
March 5, 2020

In 2016, Catalonia faced a pediatric brainstem encephalitis outbreak caused by enterovirus A71. This study improved detection of the virus in cerebrospinal fluid compared to standard qRT-PCR. Our group contributed EV71 antigens to analyze antibody responses in affected children.

Broadly neutralizing human antibodies against dengue virus identified by single B cell transcriptomics (eLife) Icon
December 10, 2019

A key goal in dengue vaccine design is to elicit antibodies that neutralize all four DENV serotypes. This study identified potent pan-DENV neutralizing antibodies from infected individuals. Our group helped by characterizing their homogeneity and oligomeric state.

Pan-viral serology implicates enteroviruses in acute flaccid myelitis (Nature Medicine) Icon
November 25, 2019

Acute flaccid myelitis (AFM) is a rare but serious polio-like illness in children. This study found evidence linking non-polio enteroviruses to AFM. Our team contributed by producing an enterovirus antigen panel to analyze antibody responses in patient cerebrospinal fluid.