About

Professor Aaron Carlin leads the Carlin Laboratory at the UCSD School of Medicine in La Jolla, California, where his research focuses on the transcriptional mechanisms that determine the outcomes of host-pathogen interactions. His lab employs a combination of genome-wide, molecular, and genetic approaches to elucidate how pathogenic viruses trigger pro- and anti-microbial transcriptional programs and how these programs contribute to immunity or pathogenesis. This research aims to provide detailed insights into why specific pathogens cause human disease, facilitate the development of rapid infectious disease diagnostics, and identify optimal targets for new antimicrobial therapies. The Carlin Lab investigates several key areas including viral manipulation of immunity, antiviral transcriptional regulation, self and non-self recognition, systems methods for host-pathogen analysis, and antimicrobial drug discovery. They study how viruses subvert innate and adaptive antiviral responses by influencing regulatory mechanisms such as gene-specific and transcription factor-specific effects, as well as global effects on transcription, splicing, and RNA stability. The lab also leverages genome-wide technologies and bioinformatics to understand transcriptional networks regulated by interferon regulatory factors and other inflammatory transcription factors, exploring how these networks induce specific antiviral gene programs. Additionally, the lab explores the role of sialic acid binding immunoglobulin type lectins (Siglecs) in self/non-self recognition and how pathogen interactions with Siglecs modulate disease pathogenesis and susceptibility. They develop and improve systems-based approaches to analyze and integrate quantitative next-generation sequencing data to better understand human-viral interactions, working closely with other UCSD laboratories to optimize experimental and computational tools. Furthermore, the Carlin Lab collaborates with chemists, microbiologists, and infectious disease physicians to develop and optimize new therapeutics for emerging infectious diseases, contributing to antimicrobial drug discovery efforts.

Research topics

• Biology
• Virology
• Biochemistry
• Medicine
• Chemistry
• Internal medicine
• Cell biology
• Molecular biology
• Neuroscience
• Immunology
• Genetics
• Pathology

Selected publications

• Engineered OAA lectins as selective and sensitive high mannose glycan targeting tools

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-06

  articleOpen access

  Abstract The Oscillatoria agardhii agglutinin (OAA) lectin interacts with N-glycans through a pentamannose core shared among all high mannose N-glycans (HMGs). Because HMGs only differ by number of mannose sugars, there is a scarcity of tools sensitive enough to resolve each specific HMG structure in their biological context. Here, we investigate the sequence space of OAA to tune the binding properties towards selectivity of Man 5 GlcNAc 2 , thus generating a structure-specific detection tool. Using phage display to screen a diverse library of OAA variants, we identify a variant with high selectivity for Man 5 GlcNAc 2 that we further dissect to reveal four mutations necessary for selectivity and two mutations responsible for enhanced affinity for all HMGs. Coupling a crystal structure of the selective variant with binding analysis of specific point mutations, we reveal how co-dependent mutations achieve selectivity. We then demonstrate how variants can be valency-modulated on a single beta-barrel scaffold to improve their binding properties by orders of magnitude. Finally, we showcase the applicability of engineered OAA variants as improved HMG profiling tools and tunable antiviral agents.

  PublisherDOI

• Interferon-inducible guanylate-binding protein 5 inhibits replication of multiple viruses by binding to the oligosaccharyltransferase complex and inhibiting glycoprotein maturation

  mBio · 2025-11-17 · 1 citations

  articleOpen access

  ABSTRACT Viral infection induces production of type I interferons and expression of interferon-stimulated genes (ISGs) that play key roles in inhibiting viral infection. Here, we show that the ISG guanylate-binding protein 5 (GBP5) inhibits N-linked glycosylation of key proteins in multiple viruses, including SARS-CoV-2 spike protein. GBP5 binds to accessory subunits of the host oligosaccharyltransferase (OST) complex and blocks its interaction with the spike protein, which results in misfolding and retention of the spike protein in the endoplasmic reticulum likely due to decreased N -glycan transfer and reduces the assembly and release of infectious virions. Consistent with these observations, pharmacological inhibition of the OST complex with NGI-1 potently inhibits glycosylation of other viral proteins, including MERS-CoV spike protein, HIV-1 gp160, and IAV hemagglutinin, and prevents the production of infectious virions. Our results identify a novel strategy by which ISGs restrict virus infection and provide a rationale for targeting glycosylation as a broad antiviral therapeutic strategy. IMPORTANCE Viral infection induces production of type I interferons and expression of interferon-stimulated genes (ISGs) that play key roles in inhibiting viral infection. We found that the interferon-stimulated gene GBP5 is induced by SARS-CoV-2 infection in vitro and in vivo . GBP5 inhibits N-glycosylation of key proteins in multiple viruses, including SARS-CoV-2. Importantly, pharmacological inhibition of oligosaccharyltransferase (OST) complex blocks host cell infection by SARS-CoV-2, variants of concern, HIV-1, and IAV, indicating future translational application of our findings.

  PublisherDOI

• Genome-Wide Interrogation of SARS-CoV-2 RNA-Protein Interactions Uncovers Hidden Regulatory Sites

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-28

  preprintOpen access

  The global impact of the COVID-19 pandemic underscores the critical need for a comprehensive understanding of SARS-CoV-2 replication mechanisms. While the central roles of the RNA dependent RNA polymerase (NSP12), primase protein (NSP8), and nucleocapsid protein (N) in the virus life cycle are extensively studied, the precise nature of their interactions with the full-length viral RNA genome remain incompletely characterized. In this study, we sought to address this knowledge gap by employing enhanced crosslinking and immunoprecipitation (eCLIP) to map the binding sites of NSP8, NSP12, and N proteins across the SARS-CoV-2 genome at early stages of viral RNA and protein synthesis and late stages of virion assembly. Our findings revealed interactions of NSP8 and NSP12 to the 5' and 3' untranslated regions (UTRs) of both positive and negative sense RNA, regions known to regulate viral replication, transcription, and translation. We identified a surprising and essential NSP12 binding site within the RNA sequence encoding the conserved Y1 domain of NSP3, which regulates RNA abundance upstream of the site. Additionally, we found that N protein interacts with the 5' UTR and influences translation efficiency. Finally, we report a novel regulatory function of N protein in modulating ribosomal frameshifting proximal to the frameshift element, a crucial process for maintaining viral protein stoichiometry. Our results provide a detailed molecular map of SARS-CoV-2 protein-RNA interactions, revealing potential therapeutic targets for attenuating viral fitness and informing the development of next-generation antiviral strategies.

  PublisherOA PDFDOI

• Zika but not Dengue virus infection limits NF-κB activity in human monocyte-derived dendritic cells and suppresses their ability to activate T cells

  Nature Communications · 2025-03-25 · 6 citations

  articleOpen access

  Understanding flavivirus immunity is critical for the development of pan-flavivirus vaccines. Dendritic cells (DC) coordinate antiviral innate and adaptive immune responses, and they can be targeted by flaviviruses as a mechanism of immune evasion. Using an unbiased genome-wide approach designed to specifically identify flavivirus-modulated pathways, we found that, while dengue virus (DENV) robustly activates DCs, Zika virus (ZIKV) causes minimal activation of genes involved in DC activation, maturation, and antigen presentation, reducing cytokine secretion and the stimulation of allogeneic and peptide-specific T cell responses. Mechanistically, ZIKV inhibits DC maturation by suppressing NF-κB p65 recruitment and the subsequent transcription of proinflammatory and DC maturation-related genes. Thus, we identify a divergence in the effects of ZIKV and DENV on the host T cell response, highlighting the need to factor such differences into the design of anti-flavivirus vaccines. Dendritic cells play pivotal roles in the immune response to viral infection but are targeted by flaviviruses resulting in evasion of the host response. Here the authors show Zika but not Dengue virus limits the NF-κB response in monocyte derived dendritic cells diminishing their ability to activate T cells.

  PublisherOA PDFDOI

• A User-Centered Service Model for Accelerating COVID-19 Diagnostic Innovation: The RADx-rad Dx Core Approach

  IEEE Open Journal of Engineering in Medicine and Biology · 2025-01-01 · 2 citations

  editorialOpen access

  The COVID-19 pandemic emphasized the urgent need for reliable diagnostic tests. To support early-stage diagnostic developers, the NIH RADx-rad Diagnostic (Dx) Core was established with two main goals: (1) to harmonize test results and streamline data submission and (2) to provide essential resources for test development. This paper describes the user-centered service model utilized by the Dx Core, detailing the resources offered and the program's impact during its four years of operation (2020–2024). The success of this model underscores its potential as a scalable framework for future diagnostic support initiatives and public health responses. As emerging infectious diseases pose challenges, this structured approach provides a blueprint for accelerating diagnostic innovation and ensuring standardized, high-quality test development in future pandemic preparedness efforts.

  PublisherDOI

• SARS-CoV-2 infectivity can be modulated through bacterial grooming of the glycocalyx

  mBio · 2025-02-25 · 2 citations

  articleOpen access

  ABSTRACT The gastrointestinal (GI) tract is a site of replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and GI symptoms are often reported by patients. SARS-CoV-2 cell entry depends upon heparan sulfate (HS) proteoglycans, which commensal bacteria that bathe the human mucosa are known to modify. To explore human gut HS-modifying bacterial abundances and how their presence may impact SARS-CoV-2 infection, we developed a task-based analysis of proteoglycan degradation on large-scale shotgun metagenomic data. We observed that gut bacteria with high predicted catabolic capacity for HS differ by age and sex, factors associated with coronavirus disease 2019 (COVID-19) severity, and directly by disease severity during/after infection, but do not vary between subjects with COVID-19 comorbidities or by diet. Gut commensal bacterial HS-modifying enzymes reduce spike protein binding and infection of authentic SARS-CoV-2, suggesting that bacterial grooming of the GI mucosa may impact viral susceptibility. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019, can infect the gastrointestinal (GI) tract, and individuals who exhibit GI symptoms often have more severe disease. The GI tract’s glycocalyx, a component of the mucosa covering the large intestine, plays a key role in viral entry by binding SARS-CoV-2’s spike protein via heparan sulfate (HS). Here, using metabolic task analysis of multiple large microbiome sequencing data sets of the human gut microbiome, we identify a key commensal human intestinal bacteria capable of grooming glycocalyx HS and modulating SARS-CoV-2 infectivity in vitro . Moreover, we engineered the common probiotic Escherichia coli Nissle 1917 (EcN) to effectively block SARS-CoV-2 binding and infection of human cell cultures. Understanding these microbial interactions could lead to better risk assessments and novel therapies targeting viral entry mechanisms.

  PublisherDOI

• Ultrasensitive detection of intact SARS-CoV-2 particles in complex biofluids using microfluidic affinity capture

  Science Advances · 2025-01-10 · 11 citations

  articleOpen access

  Measuring virus in biofluids is complicated by confounding biomolecules coisolated with viral nucleic acids. To address this, we developed an affinity-based microfluidic device for specific capture of intact severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our approach used an engineered angiotensin-converting enzyme 2 to capture intact virus from plasma and other complex biofluids. Our device leverages a staggered herringbone pattern, nanoparticle surface coating, and processing conditions to achieve detection of as few as 3 viral copies per milliliter. We further validated our microfluidic assay on 103 plasma, 36 saliva, and 29 stool samples collected from unique patients with COVID-19, showing SARS-CoV-2 detection in 72% of plasma samples. Longitudinal monitoring in the plasma revealed our device's capacity for ultrasensitive detection of active viral infections over time. Our technology can be adapted to target other viruses using relevant cell entry molecules for affinity capture. This versatility underscores the potential for widespread application in viral load monitoring and disease management.

  PublisherDOI

• Correction: Structure-selected RBM immunogens prime polyclonal memory responses that neutralize SARS-CoV-2 variants of concern

  PLoS Pathogens · 2025-11-25

  articleOpen access

  [This corrects the article DOI: 10.1371/journal.ppat.1010686.].

  PublisherOA PDFDOI

• Development of a Mouse Model of Coccidioidomycosis Using an Inhalation Exposure System

  Journal of Fungi · 2025-08-19 · 1 citations

  articleOpen access

  Coccidioides species are thermally dimorphic fungal pathogens that cause coccidioidomycosis (Valley Fever) primarily in North and South America. Coccidioides grow as hyphae that differentiate into arthroconidia, which can be aerosolized upon soil disturbance, and inhaled by the mammalian host to cause pulmonary infections with occasional dissemination to other organs. In the context of mouse models, current methods of infection include intranasal, intravenous, and intraperitoneal delivery of the arthroconidia into mice. To explore an aerosol route of infection, we compared the intranasal method with aerosolization using the Glass-Col Inhalation Exposure System (IES). Infection with a dose of 2 × 106 CFU/mL, nebulized in 5 mL of PBS, but not in water, was able to infect mice, albeit inconsistently, compared to intranasal challenge. Arthroconidia were detected inside the IES after the nebulization and decontamination cycles. These studies highlight some of the challenges with aerosolization of Coccidioides arthroconidia and serve as a reminder about biosafety considerations for use of the IES to aerosolize pathogens.

  PublisherOA PDFDOI

• Bioinformatics-Based Design Strategy and Development of an Antigen Test for SARS-CoV-2 Nucleocapsid Protein

  Preprints.org · 2024-04-01

  preprintOpen access

  The continuing mutability of the SARS-CoV-2 virus can result in failures of diagnostic assays. To address this, we describe a generalizable bioinformatics-to-biology pipeline developed for calibration and quality assurance of inactivated SARS-COV-2 variant panels provided to Radical Acceleration of Diagnostics programs (RADx)-radical program awardees. Heuristic genetic analysis based on variant-defining mutations demonstrated the lowest genetic variance in the Nucleocapsid protein (Np)- C-terminal domain (CTD) across all SARS-COV-2 variants. We then employed the Shannon entropy method on (Np) sequences collected from the major variants, verifying the CTD with lower entropy (less prone to mutations) than other Np regions. Polyclonal and monoclonal antibodies were raised against this target CTD antigen and used to develop an Enzyme-linked immunoassay (ELISA) test for SARS-CoV-2. Blinded Viral Quality Assurance (VQA) panels comprising of UV-inactivated SARS CoV-2 variants (XBB.1.5, BF.7, BA.1, B.1.617.2, and WA1) and distractor respiratory viruses (CoV 229E, CoV OC43, RSV A2, RSV B, IAV H1N1, and IBV) were assembled by the RADx-rad Diagnostics core and tested using the ELISA described here. The assay tested positive for all variants with high sensitivity (Limit of Detection: 1.72-8.78 ng/mL) and negative for the distractor virus panel. Epitope mapping for the monoclonal antibodies identified a twenty amino acid antigenic peptide on the Np-CTD that an in-silico program also predicted for the highest antigenicity. This work provides a template for a bioinformatics pipeline to select genetic regions with a low propensity for mutation (low Shannon entropy) to develop robust ‘pan-variant’ antigen-based assays for viruses prone to high mutational rates.

  PublisherOA PDFDOI

Recent grants

• Deconvolution of pro- and anti-viral responses to Dengue virus and Zika Virus infections

  NIH · $1.0M · 2019–2023

Frequent coauthors

• Alex E. Clark

  University of California, San Diego

  59 shared

• Sandra L. Leibel

  Discovery Institute

  45 shared

• Rachael N. McVicar

  33 shared

• Elizabeth M. Kwong

  University of California, San Diego

  27 shared

• Davey M. Smith

  22 shared

• Eric R. Griffis

  Imaging Center

  21 shared

• Willi Cheung

  University of California, San Diego

  21 shared

• Aaron F. Garretson

  University of California, San Diego

  21 shared