Publications

This study identifies CCDC32 as an endocytic accessory protein that directly interacts with the AP2 adaptor complex to stabilize and promote clathrin-coated pit invagination, a critical early step in clathrin-mediated endocytosis. Our group analyzed predicted structures of several CCDC32 complexes.

This study investigates the therapeutic potential of a panel of cyclodextrins (CDs) to counteract both viral infection and virus-induced endothelial dysfunction. Our group contributed to this study by recombinantly expressing and purifying viral antigens.

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 agent’s nanobodies across multiple viral variants.

Targeting the conserved N-heptad repeat (NHR) of HIV-1 gp41 has long been challenging due to its transient exposure during viral entry. In this study, machine-learning–guided antibody design was used to optimize the NHR-directed antibody D5_AR. Our group contributed by purifying a panel of monoclonal antibodies at high throughput.

Viral RNAs engage extensive networks of host RNA-binding proteins, but the functional consequences of these interactions are poorly understood. This study identifies 130 host RBPs that associate with translating poliovirus RNAs and reveals ADAR1 as a restriction factor that edits viral RNA during infection. Our group analyzed predicted structures of RBPs to assess the impact of the RNA edits on protein function.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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, 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.

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.

 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.

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.

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.

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.

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.

X-ray crystal structures of an organic anion transporter.

X-ray crystal structures of protein O-fucosyltransferase in complex with EGF-like domains.

 X-ray crystal structures of a Zn(II)/proton antiporter from a heavy metal-resistant gram-negative bacteria.

Structural and enzyme kinetic characterization of divalent metal-ion independent glycosyltransferase activity.

Methods for screening membrane protein expression and detergent solubiliaztion from transiently transfected HEK293 cells.

X-ray crystal structure of SARS1-CoV spike receptor binding domain in complex with a neutralizing mouse monoclonal antibody fragment.

Methods for mammalian cell expression of glycosyltransferases using perfusion-fed bioreactors.

Structures of branched O-linked glycosyltransferase, C2GnT, in the apo and acceptor substrate bound conformations, at 2.0 Å and 2.7 Å resolution, respectively.