About

Dr. Joseph A. Loo is a Professor in the Department of Biological Chemistry at the UCLA David Geffen School of Medicine and in the Department of Chemistry & Biochemistry at UCLA. He serves as the Faculty Director of the UCLA Mass Spectrometry and Proteomics Technology Center and is a member of several UCLA research institutes, including the UCLA/DOE Laboratory for Genomics and Proteomics, the UCLA Molecular Biology Institute, and the UCLA Jonsson Comprehensive Cancer Center. His expertise lies in the mass spectrometry characterization of proteins and their post-translational modifications, with a focus on developing bioanalytical methods for structural characterization of peptides and proteins, proteomics, and disease biomarkers. Dr. Loo has authored over 180 scientific publications and has significantly contributed to the application of electrospray ionization mass spectrometry (ESI-MS) for analyzing noncovalently-bound macromolecular assemblies and their interactions. His research includes profiling proteins in human salivary fluids for disease biomarker discovery and elucidating protein complexes and modifications in complex biological systems. He has received numerous awards and honors, including fellowships and recognition from professional societies, and has served on editorial boards for prominent journals in mass spectrometry and analytical chemistry.

Research topics

• Computer Science
• Chemistry
• Chromatography
• Computational biology
• Genetics
• Immunology
• Bioinformatics
• Cell biology
• Nanotechnology
• Medicine
• Biology

Selected publications

• Additional file 1 of GFAP degradation in TBI: linking novel modified products to astrocyte pathology and patient outcome

  Figshare · 2026-04-24

  articleOpen access

  Supplementary Material 1

  PublisherDOI

• Allosteric Modulation of Pathological Ataxin‐3 Aggregation: A Path to Spinocerebellar Ataxia Type‐3 Therapies (Adv. Sci. 11/2026)

  Advanced Science · 2026-02-01

  articleOpen access
  PublisherDOI

• Cross-Platform Assessment of Sub-50 nm Nanopipette Emitters for Native Electrospray Ionization Mass Spectrometry

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-23

  articleSenior authorCorresponding

  Native mass spectrometry (nMS) is well established for measuring protein masses and stoichiometries using nano-electrospray ionization (nESI), yet salt adduction and source activation energies can limit routine measurements. In this study, we benchmark submicron quartz nanopipette nESI emitters (<50 nm internal diameter) across three mass spectrometry platforms (quadrupole-time-of-flight, quadrupole-Orbitrap, and tribrid-Orbitrap platforms) and a wide protein mass range (17-800 kDa). We analysed holo-myoglobin (17 kDa) over a range of concentrations (10 μM-10 nM) and capillary voltages to determine limits of detection and define a gentle operating regime. We additionally observe reduced Na+ adduction and preservation of the Zn2+ bound metalloproteoform of carbonic anhydrase II (29 kDa). Proteins and protein complexes spanning the mid-to-high mass range including ovalbumin (~44 kDa), malate dehydrogenase (~70 kDa), glutamate dehydrogenase (~350 kDa), β-galactosidase (~465 kDa), and GroEL (~800 kDa), were readily detected using nanopipette emitters. Compared with conventional 1-2 μm internal diameter borosilicate emitters, quartz nanopipettes provided higher signal-to-noise ratios and fewer adducts. Finally, direct analysis of clarified bacterial lysate expressing α-synuclein yielded a clear monomeric charge-state distribution, demonstrating compatibility with complex biological matrices. Collectively, these results establish quartz nanopipette nESI as an instrument-portable, salt-tolerant approach suitable for routine nMS analysis across a broad range of protein molecular weights and sample complexities.

  PublisherDOI

• Additional file 1 of GFAP degradation in TBI: linking novel modified products to astrocyte pathology and patient outcome

  Figshare · 2026-04-24

  articleOpen access

  Supplementary Material 1

  PublisherDOI

• Native Mass Spectrometry-Based Proteomics Reveals the Mechanism of Hemophore Release by Pathogenic <i>Corynebacterium diphtheriae</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-27

  articleOpen accessSenior authorCorresponding

  Abstract Iron is an essential micronutrient for nearly all forms of life, including pathogenic microbes that must acquire it from their host during infection. At the host–pathogen interface, humans restrict microbial access to iron through nutritional immunity, which many pathogens overcome by secreting hemophores that scavenge extracellular heme (iron protoporphyrin IX). However, identifying hemophores and other ligand-binding proteins in complex proteomes remains challenging using conventional peptide-based bottom-up mass spectrometry (MS). Here, we introduce ProteoMIX (Proteome Analysis by Mixing), a function-based native top-down proteomics workflow that combines slow-mixing mode native MS with charge reduction to identify ligand-binding proteins directly from complex mixtures. Applying ProteoMIX to the Corynebacterium diphtheriae exoproteome identified ChtA 30–314 , an abundant soluble hemophore generated by proteolytic processing of the surface-exposed ChtA heme receptor. Using native top-down MS sequencing, cell fractionation, and gene deletion, we show that the protease DIP2069 releases ChtA 30–314 by removing ChtA’s transmembrane helix, producing a soluble proteoform that delivers heme to support microbial growth. In contrast, the related paralog ChtC is not processed, enabling C. diphtheriae to generate localization-specific heme-binding proteoforms from related gene products. Extending this approach to Staphylococcus aureus , ProteoMIX also revealed soluble IsdA hemophores that coexist with surface-anchored variants, demonstrating the generality of the method and suggesting that protease-mediated hemophore release may operate across gram-positive pathogens.

  PublisherOA PDFDOI

• MassIVE MSV000101762 - Visual exoproteomics of Clostridium thermocellum during anaerobic biomass-degradation identifies functional spirosomes

  UC San Diego · 2026-01-01

  datasetOpen accessSenior author
  PublisherDOI

• Science for the Masses

  Journal of the American Society for Mass Spectrometry · 2026-05-06

  article1st authorCorresponding
  PublisherDOI

• Identification of diagnostic fragments of S-nitrosohemoglobin using native top-down mass spectrometry

  Pepperdine Digital Commons (Pepperdine University) · 2026-04-10

  articleSenior author

  Hemoglobin (Hb) is the oxygen-carrying protein in mammals and is probably the most studied protein in history. One ongoing area of Hb research is the mechanism of Hb transport and release of nitric oxide. Nitric oxide (NO) is an essential regulatory molecule in humans and other animals that helps control constriction and relaxation of blood vessels, thereby regulating the flow of blood throughout the organism. It has been postulated that Hb transports NO in blood as a nitrosothiol at Cys93 of the β-globin chain of Hb and then releases NO upon heme deoxygenation in capillaries. This project uses native top-down MS to identify diagnostic signals from S-nitrosohemoglobin (SNO-Hb). Native top-down MS was used to analyze a series of SNO-Hb samples treated with increasing concentrations of the NO donor SNO-Cys. The data set was analyzed to identify correlations between top-down fragmentation patterns and the relative quantity of SNO-Hb compared to Hb in a mixture. Signal intensity in both raw and deconvoluted spectra were analyzed using a variety of methods including principal components analysis (PCA) and comparisons of intensity deviations from computed median absolute deviation (MAD) values across multiple spectra. Native and top-down experiments were performed using a UHMR Orbitrap MS instrument. Previous studies have analyzed SNO-Hb using both intact and tryptic digest methods, however these previous studies reported challenges in the analysis of SNO-Hb caused by dissociation of the unstable S-nitroso bond. Dissociation of the NO can lead to radical-induced dissociation, further complicating native and top-down results. To address the challenge of interpreting this data, we used a combination of statistical analysis workflows to seek to identify diagnostic signals corresponding to SNO-Hb fragments. Both deconvoluted data sets and raw spectra were analyzed independently to identify common features. The relative intensity values of the diagnostic fragments may enable future quantitative studies of SNO-Hb from biological samples.

  Publisher

• Combining MicroED and native mass spectrometry for structural discovery of enzyme–small molecule complexes

  Proceedings of the National Academy of Sciences · 2025-07-28 · 4 citations

  articleOpen access

  With the goal of accelerating the discovery of small molecule-protein complexes, we leverage fast, low-dose, event-based electron counting microcrystal electron diffraction (MicroED) data collection and native mass spectrometry. This approach, which we term electron diffraction with native mass spectrometry (ED-MS), allows assignment of protein target structures bound to ligands with data obtained from crystal slurries soaked with mixtures of known inhibitors and crude biosynthetic reactions. This extends to libraries of printed ligands dispensed directly onto TEM grids for later soaking with microcrystal slurries, and complexes with noncovalent ligands. ED-MS resolves structures of the natural product, epoxide-based cysteine protease inhibitor E-64, and its biosynthetic analogs bound to the model cysteine protease, papain. It further identifies papain binding to its preferred natural products, by showing that two analogs of E-64 outcompete others in binding to papain crystals, and by detecting papain bound to E-64 and an analog from crude biosynthetic reactions, without purification. ED-MS also resolves binding of the CTX-M-14 β-lactamase, a target of active drug development, to the non-β-lactam inhibitor, avibactam, alone or in a cocktail of unrelated compounds. These results illustrate the utility of ED-MS for natural product ligand discovery and for structure-based screening of small molecule binders to macromolecular targets, promising utility for drug discovery.

  PublisherOA PDFDOI

• Leveraging bioorthogonal conjugation for alpha synuclein fibril surveillance

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-17

  preprintOpen access

  Abstract Alpha synuclein (α-syn) amyloid fibrils are associated with various neurodegenerative diseases. To better understand the molecular and cellular basis for α-syn fibril persistence and spread, we implemented a fluorophore labeling strategy to surveil pre-formed α-syn fibrils in solution and in cells. We leveraged amber codon mediated incorporation of a tetrazine-based artificial amino acid (TetV2.0) to install a cyclooctene-conjugated Janeliaflour, JF549, at four sites on human α-syn: residues 4, 60, 96 and 136. Fast coupling occurred under mild buffer conditions and in the presence of the disease-associated cofactor and cytotoxic lipid, psychosine. Labeled fibrils retained their polymorphic features, seeded the growth of new fibrils in vitro , and induced the seeding of positive puncta in α-syn FRET biosensor HEK293T cells. This allowed simultaneous tracking of exogenous and endogenous α-syn aggregates in biosensor cells, and their localization within the cells. In doing so, our approach facilitates more detailed mechanistic investigation of α-syn aggregates.

  PublisherOA PDFDOI

Recent grants

• Advancing Mass Spectrometry Analyses of Proteins, Assemblies, and Proteoforms

  NIH · $1.9M · 2022–2027

• NIH Grant S10RR028893

  NIH · $2.7M · 2011

• Mass Spectrometry of Protein Assemblies

  NIH · $3.2M · 2004–2024

• NIH Grant R21GM103531

  NIH · $390k · 2015

• NIH Grant R01RR020004

  NIH · $2.7M · 2013

Frequent coauthors

• Rachel R. Ogorzalek Loo

  University of California, Los Angeles

  197 shared

• John R. Yates

  Scripps Research Institute

  112 shared

• Carolyn R. Bertozzi

  Stanford University

  87 shared

• Laura L. Kiessling

  Massachusetts Institute of Technology

  87 shared

• Anne B. McCoy

  University of Washington

  85 shared

• Kenneth M. Merz

  Michigan State University

  85 shared

• Gregory D. Scholes

  Princeton University

  85 shared

• Jillian M. Buriak

  University of Alberta

  85 shared

Labs

• Loo, Joseph A. LaboratoryPI

Awards & honors

• Clarkson U. American Chemical Society Analytical Chemistry D…
• Clarkson U. Chemical Rubber Company Achievement Award
• Clarkson U. George L. Jones, Jr. Memorial Award
• Clarkson U. Merck Chemistry Award
• Cornell Chemistry Teaching Assistant Award