Aaron M. Ring

Aaron M. Ring

Yale University

H-index: 45

North America-United States

About Aaron M. Ring

Aaron M. Ring, With an exceptional h-index of 45 and a recent h-index of 39 (since 2020), a distinguished researcher at Yale University, specializes in the field of Protein engineering, Systems immunology, Immunotherapy.

His recent articles reflect a diverse array of research interests and contributions to the field:

Compartmentalized ocular lymphatic system mediates eye–brain immunity

Decoding the autoantibody reactome

Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naÏve individuals with Long COVID

A host–microbiota interactome reveals extensive transkingdom connectivity

Biological and clinical roles of IL-18 in inflammatory diseases

Decoy-resistant IL-18 enhances checkpoint inhibitor combinations beyond anti-PD-1 in vitro and in vivo

Interleukin-18 variants and methods of use

Investigating Autoantibody Profiles in Seronegative Myasthenia Gravis (P1-5.005)

Aaron M. Ring Information

University

Yale University

Position

Assistant Professor of Immunobiology

Citations(all)

15682

Citations(since 2020)

12485

Cited By

6705

hIndex(all)

45

hIndex(since 2020)

39

i10Index(all)

75

i10Index(since 2020)

75

Email

University Profile Page

Yale University

Aaron M. Ring Skills & Research Interests

Protein engineering

Systems immunology

Immunotherapy

Top articles of Aaron M. Ring

Compartmentalized ocular lymphatic system mediates eye–brain immunity

Authors

Xiangyun Yin,Sophia Zhang,Ju Hyun Lee,Huiping Dong,George Mourgkos,Gordon Terwilliger,Aurora Kraus,Luiz Henrique Geraldo,Mathilde Poulet,Suzanne Fischer,Ting Zhou,Farrah Shalima Mohammed,Jiangbing Zhou,Yongfu Wang,Seth Malloy,Nicolas Rohner,Lokesh Sharma,Irene Salinas,Anne Eichmann,Jean-Leon Thomas,W Mark Saltzman,Anita Huttner,Caroline Zeiss,Aaron Ring,Akiko Iwasaki,Eric Song

Journal

Nature

Published Date

2024/2/28

The eye, an anatomical extension of the central nervous system (CNS), exhibits many molecular and cellular parallels to the brain. Emerging research demonstrates that changes in the brain are often reflected in the eye, particularly in the retina. Still, the possibility of an immunological nexus between the posterior eye and the rest of the CNS tissues remains unexplored. Here, studying immune responses to herpes simplex virus in the brain, we observed that intravitreal immunization protects mice against intracranial viral challenge. This protection extended to bacteria and even tumours, allowing therapeutic immune responses against glioblastoma through intravitreal immunization. We further show that the anterior and posterior compartments of the eye have distinct lymphatic drainage systems, with the latter draining to the deep cervical lymph nodes through lymphatic vasculature in the optic nerve sheath. This …

Decoding the autoantibody reactome

Authors

Jillian R Jaycox,Yile Dai,Aaron M Ring

Journal

Science

Published Date

2024/2/16

Investigating the causes of individual variation in health outcomes has led to transformative insights into human biology and advances in nearly every branch of medicine. Historically, emphasis has been placed on how genetic factors contribute to phenotypic variation within populations. However, an emerging concept is that self-reactive antibodies (autoantibodies) represent a critical yet largely underexplored factor that influences human health and disease. Investigating autoantibodies and their protective as well as pathological roles in disease may unlock new treatment paradigms, much like the prior study of genetics.

Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naÏve individuals with Long COVID

Authors

Connor B Grady,Bornali Bhattacharjee,Julio Silva,Jillian Jaycox,Lik Wee Lee,Valter Silva Monteiro,Mitsuaki Sawano,Daisy Massey,César Caraballo,Jeff R Gehlhausen,Alexandra Tabachnikova,Tianyang Mao,Carolina Lucas,Mario A Pena-Hernandez,Lan Xu,Tiffany J Tzeng,Takehiro Takahashi,Jeph Herrin,Diana Berrent Güthe,Athena Akrami,Gina Assaf,Hannah Davis,Karen Harris,Lisa McCorkell,Wade L Schulz,Daniel Grffin,Hannah Wei,Aaron M Ring,Leying Guan,Charles Dela Cruz,Akiko Iwasaki,Harlan M Krumholz

Journal

medRxiv

Published Date

2024/1/12

BackgroundLong COVID contributes to the global burden of disease. Proposed root cause hypotheses include the persistence of SARS-CoV-2 viral reservoir, autoimmunity, and reactivation of latent herpesviruses. Patients have reported various changes in Long COVID symptoms after COVID-19 vaccinations, leaving uncertainty about whether vaccine-induced immune responses may alleviate or worsen disease pathology.MethodsIn this prospective study, we evaluated changes in symptoms and immune responses after COVID-19 vaccination in 16 vaccine-naïve individuals with Long COVID. Surveys were administered before vaccination and then at 2, 6, and 12 weeks after receiving the first vaccine dose of the primary series. Simultaneously, SARS-CoV-2-reactive TCR enrichment, SARS-CoV-2-specific antibody responses, antibody responses to other viral and self-antigens, and circulating cytokines were …

A host–microbiota interactome reveals extensive transkingdom connectivity

Authors

Nicole D Sonnert,Connor E Rosen,Andrew R Ghazi,Eric A Franzosa,Brianna Duncan-Lowey,Jaime A González-Hernández,John D Huck,Yi Yang,Yile Dai,Tyler A Rice,Mytien T Nguyen,Deguang Song,Yiyun Cao,Anjelica L Martin,Agata A Bielecka,Suzanne Fischer,Changhui Guan,Julia Oh,Curtis Huttenhower,Aaron M Ring,Noah W Palm

Journal

Nature

Published Date

2024/4

The myriad microorganisms that live in close association with humans have diverse effects on physiology, yet the molecular bases for these impacts remain mostly unknown 1, 2, 3. Classical pathogens often invade host tissues and modulate immune responses through interactions with human extracellular and secreted proteins (the ‘exoproteome’). Commensal microorganisms may also facilitate niche colonization and shape host biology by engaging host exoproteins; however, direct exoproteome–microbiota interactions remain largely unexplored. Here we developed and validated a novel technology, BASEHIT, that enables proteome-scale assessment of human exoproteome–microbiome interactions. Using BASEHIT, we interrogated more than 1.7 million potential interactions between 519 human-associated bacterial strains from diverse phylogenies and tissues of origin and 3,324 human exoproteins. The …

Biological and clinical roles of IL-18 in inflammatory diseases

Authors

Emily Landy,Hallie Carol,Aaron Ring,Scott Canna

Published Date

2024/1

Several new discoveries have revived interest in the pathogenic potential and possible clinical roles of IL-18. IL-18 is an IL-1 family cytokine with potent ability to induce IFNγ production. However, basic investigations and now clinical observations suggest a more complex picture. Unique aspects of IL-18 biology at the levels of transcription, activation, secretion, neutralization, receptor distribution and signalling help to explain its pleiotropic roles in mucosal and systemic inflammation. Blood biomarker studies reveal a cytokine for which profound elevation, associated with detectable ‘free IL-18’, defines a group of autoinflammatory diseases in which IL-18 dysregulation can be a primary driving feature, the so-called ‘IL-18opathies’. This impressive specificity might accelerate diagnoses and identify patients amenable to therapeutic IL-18 blockade. Pathogenically, human and animal studies identify a preferential …

Decoy-resistant IL-18 enhances checkpoint inhibitor combinations beyond anti-PD-1 in vitro and in vivo

Authors

Jeffrey N Lindquist,Kai Qin,Aaron M Ring,Hirdesh Uppal

Journal

Cancer Research

Published Date

2024/3/22

Background: Interleukin-18 (IL18) is a proinflammatory cytokine that modulates both innate and adaptive immune responses. Historically, wild-type recombinant IL-18 has shown limited anti-tumor efficacy in preclinical models and clinical trials, likely due to upregulation of IL-18 binding protein (IL-18BP), a negative regulator of the IL-18 signaling axis. Accordingly, an engineered IL-18 cytokine capable of interacting with the IL-18 receptor, but resistant to IL-18BP interactions (i.e., “Decoy-Resistant IL-18”, DR-18), has demonstrated enhanced therapeutic potential in mouse tumor models, both as a single agent and in combination with anti-PD-1 [1, 2]. Here we evaluated murine DR-18 in combination with additional checkpoint inhibitors beyond anti-PD-1 in a set of mouse tumor models, and tested human DR-18 activity in vitro/ex vivo for activation of human immune cells and anti-tumor activity. Results: Treatment with …

Interleukin-18 variants and methods of use

Published Date

2023/11/9

The present invention provides compositions and methods comprising an activator of IL-18 activity for use in therapeutic and non-therapeutic applications. The activator provides IL-18 signaling activity even in the presence of an inhibitory molecule such as IL-18BP.

Investigating Autoantibody Profiles in Seronegative Myasthenia Gravis (P1-5.005)

Authors

Gianvito Masi,Minh C Pham,Yile Dai,Yingkai Li,Tabitha Karatz,Seneca R Oxendine,Vern Juel,Aaron M Ring,Richard Nowak,Jeff Guptill,Kevin C O’Connor

Published Date

2023/4/25

Objective: To refine the serological characterization of patients with seronegative myasthenia gravis (SNMG) and explore novel disease-specific autoantibody reactivities. Background: MG is characterized by a detrimental humoral response against key proteins on the neuromuscular junction, including the acetylcholine receptor (AChR) and muscle-specific tyrosine kinase (MuSK). In about 10% of MG patients, defined as seronegative, a lack of detectable autoantibodies by radioimmunoassay hampers a prompt diagnosis and restricts eligibility for clinical trials and payers’ reimbursement for certain therapies. In variable proportions of SNMG patients, autoantibodies can be detected by cell-based assays (CBA). However, data on CBA positivity rates in the US are lacking. Moreover, the prevalence of low-density lipoprotein receptor-related protein 4 (LRP4) autoantibodies, and the presence of autoantibodies against yet unidentified muscle autoantigens, remain uncertain in SNMG. Design/Methods …

Targeting host-bacteria interactions for the treatment of microbiota-mediated diseases

Published Date

2023/12/21

The present invention generally relates to compositions and methods for modulating specific paired host protein-microbiota interactions and the use thereof for the prevention and treatment of diseases and disorders.

Developing synthetic tools to decipher the tumor–immune interactome

Authors

and Akiko Iwasakia Orr-El Weizmana,Sophia Luytena,Peiwen Lua,Eric Songa,b,Kai Qina,Darius Mostaghimia,Aaron M. Ringa

Journal

Proceedings of the National Academy of Sciences

Published Date

2023/10/23

The ability of immune cells to directly interact with transformed cells is an essential component of immune surveillance and critical for optimal tissue function. The tumor–immune interactome (the collective cellular interactions between oncogenic cells and immune cells) is distinct and varied based on the tissue location and immunogenicity of tumor subtypes. However, comprehensive landscape and the consequences of tumor-interacting immune cells in the tumor microenvironment are not well understood. Current tools are limited in their ability to identify and record interactors in vivo or be utilized for downstream analysis. Here, we describe the development and validation of a technology leveraging synthetic Notch receptors reporting physical tumor cell–immune cell contact in vivo in order to decipher the tumor–immune interactome. We call this approach, Tumor–Immune Interactome Non-biased Discovery …

Superagonists, partial agonists and antagonists of interleukin-2

Published Date

2022/7/12

Novel human interleukin-2 (IL-2) muteins or variants thereof are provided. In particular, provided are IL-2 muteins that have an increased binding capacity for IL-2Rβ receptor and a decreased binding capacity for IL-2Rγc receptor, as compared to wild-type IL-2. Such IL-2 muteins are useful, for example, as IL-2 partial agonist and antagonists in applications where reduction or inhibition of one or more IL-2 and/or IL-15 functions is useful (eg, in the treatment of graft versus host disease (GVHD) and adult T cell leukemia). Also provided are nucleic acids encoding such IL-2 muteins, methods of making such IL-2 muteins, pharmaceutical compositions that include such IL-2 muteins and methods of treatment using such pharmaceutical compositions.

IL-18BP mediates the balance between protective and pathological immune responses to Toxoplasma gondii

Authors

Joseph T Clark,Orr-El Weizman,Daniel L Aldridge,Lindsey A Shallberg,Julia Eberhard,Zachary Lanzar,Devon Wasche,John D Huck,Ting Zhou,Aaron M Ring,Christopher A Hunter

Journal

Cell reports

Published Date

2023/3/28

Interleukin-18 (IL-18) promotes natural killer (NK) and T cell production of interferon (IFN)-γ, a key factor in resistance to Toxoplasma gondii, but previous work has shown a limited role for endogenous IL-18 in control of this parasite. Although infection with T. gondii results in release of IL-18, the production of IFN-γ induces high levels of the IL-18 binding protein (IL-18BP). Antagonism of IL-18BP with a "decoy-to-the-decoy" (D2D) IL-18 construct that does not signal but rather binds IL-18BP results in enhanced innate lymphoid cell (ILC) and T cell responses and improved parasite control. In addition, the use of IL-18 resistant to IL-18BP ("decoy-resistant" IL-18 [DR-18]) is more effective than exogenous IL-18 at promoting innate resistance to infection. DR-18 enhances CD4+ T cell production of IFN-γ but results in CD4+ T cell-mediated pathology. Thus, endogenous IL-18BP restrains aberrant immune pathology, and …

Disrupting FC receptor engagement on macrophages enhances efficacy of anti-SIRPalpha antibody therapy

Published Date

2023/8/8

Anti-SIRPα antibodies, including multi-specific anti-SIRPα antibodies, are provided, as are related compositions and methods. The antibodies of the disclosure bind to SIRPα and can block the interaction of CD47 on one cell with SIRPα on a phagocytic cell. The subject anti-SIRPα antibodies find use in various therapeutic methods. Embodiments of the disclosure include isolated antibodies and derivatives and fragments thereof, pharmaceutical formulations comprising one or more of the anti-SIRPα antibodies; and cell lines that produce the antibodies. Also provided are amino acid sequences of exemplary anti-SIRPα antibodies.

A modified IL-18 drug in combination with CTLA-4 blockade enhances anti-tumor efficacy in preclinical models of renal cell carcinoma

Authors

David Schoenfeld,Dijana Djureinovic,Lin Zhang,Jacqueline Mann,John Huck,Lucia Jilaveanu,Aaron Ring,Harriet Kluger

Journal

NaN

Published Date

2023

BackgroundCytokine-based drugs are currently being explored as alternative cancer immunotherapies. While the cytokine interleukin-18 (IL-18) has immunostimulatory effects, it is negatively regulated by a secreted high-affinity binding protein, IL-18BP, that functions as an immune checkpoint that limits IL-18’s efficacy as a cancer therapeutic. A modified version of IL-18, termed “decoy-resistant” or DR-18, that can avoid trapping by IL-18BP while still maintaining its immune signaling potential, has recently been developed. DR-18 has shown promising preclinical activity in melanoma and colorectal murine models, including potential synergy with anti-PD-1 therapy, and is currently in Phase I trials. In this study, we aim to test the efficacy and determine the cellular mechanism of action of DR-18 in combination with immune checkpoint inhibitors (ICIs) in immunocompetent preclinical models of renal cell carcinoma (RCC), with the goal of establishing the basis for testing these combinations in early phase clinical trials.MethodsWe engrafted tumors subcutaneously using two different syngeneic, immunocompetent murine RCC models: Renca and RAG. Mice were treated with single-agent DR-18 and combinations of DR-18 with single-and dual-agent anti-PD-1 and anti-CTLA-4. Tumor growth and survival were monitored. In the Renca model, plasma was collected at early time-points and cytokine/chemokine levels were profiled using a 31-plex discovery assay. Single-cell RNA and TCR sequencing was also performed on Renca tumors. Additionally, immune cell depletion studies were conducted in the Renca model with antibodies targeting CD8, CD4 …

High affinity PD-1 agents and methods of use

Published Date

2023/11/14

High affinity PD-1 mimic polypeptides are provided, which (i) comprise at least one amino acid change relative to a wild-type PD-1 protein; and (ii) have an increased affinity for PD-L1 relative to the wild-type protein. Compositions and methods are provided for modulating the activity of immune cells in a mammal by administering a therapeutic dose of a pharmaceutical composition comprising a high affinity PD-1 mimic polypeptide, which blocks the physiological binding interaction between PD-1 and its ligand PD-L1 and/or PD-L2.

SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity

Authors

Jillian R Jaycox,Carolina Lucas,Inci Yildirim,Yile Dai,Eric Y Wang,Valter Monteiro,Sandra Lord,Jeffrey Carlin,Mariko Kita,Jane H Buckner,Shuangge Ma,Melissa Campbell,Albert Ko,Saad Omer,Carrie L Lucas,Cate Speake,Akiko Iwasaki,Aaron M Ring

Journal

Nature communications

Published Date

2023/3/9

mRNA-based vaccines dramatically reduce the occurrence and severity of COVID-19, but are associated with rare vaccine-related adverse effects. These toxicities, coupled with observations that SARS-CoV-2 infection is associated with autoantibody development, raise questions whether COVID-19 vaccines may also promote the development of autoantibodies, particularly in autoimmune patients. Here we used Rapid Extracellular Antigen Profiling to characterize self- and viral-directed humoral responses after SARS-CoV-2 mRNA vaccination in 145 healthy individuals, 38 patients with autoimmune diseases, and 8 patients with mRNA vaccine-associated myocarditis. We confirm that most individuals generated robust virus-specific antibody responses post vaccination, but that the quality of this response is impaired in autoimmune patients on certain modes of immunosuppression. Autoantibody dynamics are …

Highly multiplexed bioactivity screening reveals human and microbiota metabolome-GPCRome interactions

Authors

Haiwei Chen,Connor E Rosen,Jaime A González-Hernández,Deguang Song,Jan Potempa,Aaron M Ring,Noah W Palm

Journal

Cell

Published Date

2023/7/6

The human body contains thousands of metabolites derived from mammalian cells, the microbiota, food, and medical drugs. Many bioactive metabolites act through the engagement of G-protein-coupled receptors (GPCRs); however, technological limitations constrain current explorations of metabolite-GPCR interactions. Here, we developed a highly multiplexed screening technology called PRESTO-Salsa that enables simultaneous assessment of nearly all conventional GPCRs (>300 receptors) in a single well of a 96-well plate. Using PRESTO-Salsa, we screened 1,041 human-associated metabolites against the GPCRome and uncovered previously unreported endogenous, exogenous, and microbial GPCR agonists. Next, we leveraged PRESTO-Salsa to generate an atlas of microbiome-GPCR interactions across 435 human microbiome strains from multiple body sites, revealing conserved patterns of cross …

Rapid extracellular antibody profiling (reap) for the discovery and use of said antibodies

Published Date

2023/11/9

The present invention relates to methods for a sensitive and high-throughput detection of various antibodies and targets thereof. For example, in one aspect, methods of the present invention can successfully detect autoantibodies against extracellular and secreted proteins. In various embodiments, the present invention provides methods of diagnosing, assessing prognosis, preventing, and treating diseases or disorders associated with antibodies or targets thereof detected via the high-throughput detection methods of the present invention.

Basehit, a high-throughput assay to identify proteins involved in host-microbe interaction

Published Date

2023/6/6

The invention provides a BASEHIT screening method for identifying proteins that are involved in host-microbe interactions which may function as therapeutic targets.

Continuous population-level monitoring of SARS-CoV-2 seroprevalence in a large European metropolitan region

Authors

Marc Emmenegger,Elena De Cecco,David Lamparter,Raphaël PB Jacquat,Julien Riou,Dominik Menges,Tala Ballouz,Daniel Ebner,Matthias M Schneider,Itzel Condado Morales,Berre Doğançay,Jingjing Guo,Anne Wiedmer,Julie Domange,Marigona Imeri,Rita Moos,Chryssa Zografou,Leyla Batkitar,Lidia Madrigal,Dezirae Schneider,Chiara Trevisan,Andres Gonzalez-Guerra,Alessandra Carrella,Irina L Dubach,Catherine K Xu,Georg Meisl,Vasilis Kosmoliaptsis,Tomas Malinauskas,Nicola Burgess-Brown,Ray Owens,Stephanie Hatch,Juthathip Mongkolsapaya,Gavin R Screaton,Katharina Schubert,John D Huck,Feimei Liu,Florence Pojer,Kelvin Lau,David Hacker,Elsbeth Probst-Müller,Carlo Cervia,Jakob Nilsson,Onur Boyman,Lanja Saleh,Katharina Spanaus,Arnold von Eckardstein,Dominik J Schaer,Nenad Ban,Ching-Ju Tsai,Jacopo Marino,Gebhard FX Schertler,Nadine Ebert,Volker Thiel,Jochen Gottschalk,Beat M Frey,Regina R Reimann,Simone Hornemann,Aaron M Ring,Tuomas PJ Knowles,Milo A Puhan,Christian L Althaus,Ioannis Xenarios,David I Stuart,Adriano Aguzzi

Journal

Iscience

Published Date

2023/2/17

Effective public health measures against SARS-CoV-2 require granular knowledge of population-level immune responses. We developed a Tripartite Automated Blood Immunoassay (TRABI) to assess the IgG response against three SARS-CoV-2 proteins. We used TRABI for continuous seromonitoring of hospital patients and blood donors (n = 72′250) in the canton of Zurich from December 2019 to December 2020 (pre-vaccine period). We found that antibodies waned with a half-life of 75 days, whereas the cumulative incidence rose from 2.3% in June 2020 to 12.2% in mid-December 2020. A follow-up health survey indicated that about 10% of patients infected with wildtype SARS-CoV-2 sustained some symptoms at least twelve months post COVID-19. Crucially, we found no evidence of a difference in long-term complications between those whose infection was symptomatic and those with asymptomatic acute …

See List of Professors in Aaron M. Ring University(Yale University)

Aaron M. Ring FAQs

What is Aaron M. Ring's h-index at Yale University?

The h-index of Aaron M. Ring has been 39 since 2020 and 45 in total.

What are Aaron M. Ring's top articles?

The articles with the titles of

Compartmentalized ocular lymphatic system mediates eye–brain immunity

Decoding the autoantibody reactome

Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naÏve individuals with Long COVID

A host–microbiota interactome reveals extensive transkingdom connectivity

Biological and clinical roles of IL-18 in inflammatory diseases

Decoy-resistant IL-18 enhances checkpoint inhibitor combinations beyond anti-PD-1 in vitro and in vivo

Interleukin-18 variants and methods of use

Investigating Autoantibody Profiles in Seronegative Myasthenia Gravis (P1-5.005)

...

are the top articles of Aaron M. Ring at Yale University.

What are Aaron M. Ring's research interests?

The research interests of Aaron M. Ring are: Protein engineering, Systems immunology, Immunotherapy

What is Aaron M. Ring's total number of citations?

Aaron M. Ring has 15,682 citations in total.

    academic-engine

    Useful Links