Aaron Esser-Kahn

Aaron Esser-Kahn

University of Chicago

H-index: 28

North America-United States

About Aaron Esser-Kahn

Aaron Esser-Kahn, With an exceptional h-index of 28 and a recent h-index of 24 (since 2020), a distinguished researcher at University of Chicago, specializes in the field of immuno-engineering, vaccines, chemistry, polymer science, adaptive materials.

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

Novel non-immunogenic trained immunity inducing small molecule with improved anti-tumor properties

Polymer Patterning by Laser-Induced Multipoint Initiation of Frontal Polymerization

An anti-Brownian magnetic feedback trap for bio-orthogonal manipulation of nanoparticles

Evidence of collective influence in innate sensing using fluidic force microscopy

Protocol for localized macrophage stimulation with small-molecule TLR agonist via fluidic force microscopy

High-throughput screening identification of novel immunomodulatory combinations for the generation of tolerogenic dendritic cells

Patterned polymer manufacturing by laser-ignited multi-initiation-point frontal polymerization

β-glucan induced trained immunity enhances antibody levels in a vaccination model in mice

Aaron Esser-Kahn Information

University

University of Chicago

Position

___

Citations(all)

4266

Citations(since 2020)

2318

Cited By

2855

hIndex(all)

28

hIndex(since 2020)

24

i10Index(all)

57

i10Index(since 2020)

49

Email

University Profile Page

University of Chicago

Aaron Esser-Kahn Skills & Research Interests

immuno-engineering

vaccines

chemistry

polymer science

adaptive materials

Top articles of Aaron Esser-Kahn

Novel non-immunogenic trained immunity inducing small molecule with improved anti-tumor properties

Authors

Jainu Ajit,Hannah Riley Knight,Qing Chen,Ani Solanki,Jingjing Shen,Aaron P Esser-Kahn

Journal

bioRxiv

Published Date

2024

Trained immunity refers to the non-specific innate immune memory response triggered by the epigenetic and metabolic rewiring of innate immune cells. A strengthened innate immune system significantly improves disease resistance. However, very few trained immunity-inducing molecules have been identified. Almost all molecules for training are primarily immunogenic and then subsequently induce training. Non-immunogenic molecules that induce training could be employed in therapies without the concern of adverse inflammatory reactions. We identified a small molecule, A1155463, that modulates cellular metabolism to induce trained immunity in macrophages in-vitro. We show that nanomolar concentrations of these compounds uniquely alter only cellular metabolism without leading to apoptosis. We further observed that these compounds could induce training in an in-vivo model in mice. A1155463 training improved anti-tumor resistance to B16.F10 melanoma cells. The effect was enhanced upon combination with checkpoint therapy. In summary, we report the discovery of a novel trained immunity-inducing small molecule with enhanced anti-tumor properties.

Polymer Patterning by Laser-Induced Multipoint Initiation of Frontal Polymerization

Authors

Andrés L Cook,Mason A Dearborn,Trevor M Anderberg,Kavya Vaidya,Justin E Jureller,Aaron P Esser-Kahn,Allison H Squires

Journal

ACS Applied Materials & Interfaces

Published Date

2024/2/28

Frontal polymerization (FP) is an approach for thermosetting plastics at a lower energy cost than an autoclave. The potential to generate simultaneous propagation of multiple polymerization fronts has been discussed as an exciting possibility. However, FP initiated at more than two points simultaneously has not been demonstrated. Multipoint initiation could enable both large-scale material fabrication and unique pattern generation. Here, the authors present laser-patterned photothermal heating as a method for simultaneous initiation of FP at multiple locations in a 2-D sample. Carbon black particles are mixed into liquid resin (dicyclopentadiene) to enhance absorption of light from a Ti:sapphire laser (800 nm) focused on a sample. The laser is time-shared by rapid steering among initiation points, generating polymerization using up to seven simultaneous points of initiation. This process results in the formation of …

An anti-Brownian magnetic feedback trap for bio-orthogonal manipulation of nanoparticles

Authors

Trevor Anderberg,Andres Cook,Kepler Domurat-Sousa,Ayesha Ejaz,Kyle Lin,Justin E Jureller,Aaron Esser-Kahn,Allison Squires

Journal

Biophysical Journal

Published Date

2024/2/8

Precise, non-invasive spatial manipulation of protein-sized objects within cellular environments remains a frontier of experimental biophysics. Magnetic fields provide an attractive option for actuation in cellulo because they are nearly bio-orthogonal: magnetic fields can be used to apply remote forces to a paramagnetic particle without perturbing biological material. While magnetic tweezers are a well-established platform for applying forces and measuring torques on tethered magnetic microparticles, transitioning this technique to untethered nanoparticles is challenging but essential for intracellular manipulation. To accomplish this, we have developed an anti-Brownian magnetic trap that allows for precise manipulation of paramagnetic nanoparticles in cellular environments. The trap utilizes closed-loop feedback with a bandwidth exceeding 1 kHz to actively counteract the Brownian motion of a magnetic particle …

Evidence of collective influence in innate sensing using fluidic force microscopy

Authors

Elizabeth J Mulder,Brittany Moser,Jennifer Delgado,Rachel C Steinhardt,Aaron P Esser-Kahn

Journal

Frontiers in Immunology

Published Date

2024/1/23

The innate immune system initiates early response to infection by sensing molecular patterns of infection through pattern-recognition receptors (PRRs). Previous work on PRR stimulation of macrophages revealed significant heterogeneity in single cell responses, suggesting the importance of individual macrophage stimulation. Current methods either isolate individual macrophages or stimulate a whole culture and measure individual readouts. We probed single cell NF-κB responses to localized stimuli within a naïve culture with Fluidic Force Microscopy (FluidFM). Individual cells stimulated in naïve culture were more sensitive compared to individual cells in uniformly stimulated cultures. In cluster stimulation, NF-κB activation decreased with increased cell density or decreased stimulation time. Our results support the growing body of evidence for cell-to-cell communication in macrophage activation, and limit potential mechanisms. Such a mechanism might be manipulated to tune macrophage sensitivity, and the density-dependent modulation of sensitivity to PRR signals could have relevance to biological situations where macrophage density increases.

Protocol for localized macrophage stimulation with small-molecule TLR agonist via fluidic force microscopy

Authors

Elizabeth J Mulder,Brittany Moser,Jennifer Delgado,Rachel Steinhardt,Aaron P Esser-Kahn

Journal

STAR protocols

Published Date

2024/3/15

Here, we present a protocol to deliver nanoliter volumes of Toll-like receptor (TLR) agonist onto a culture of nuclear factor κB (NF-κB) reporter macrophages using fluidic force microscopy and a micron-scale probe. We describe steps for quantifying the dose of agonist by modeling their diffusion with experimental inputs. We then detail procedures for quantifying and categorizing macrophage responses to individual and varied doses and combining agonist concentration and macrophage response to analyze the NF-κB response to localized TLR stimulation.For complete details on the use and execution of this protocol, please refer to Mulder et al. (2024).1

High-throughput screening identification of novel immunomodulatory combinations for the generation of tolerogenic dendritic cells

Authors

Sihan Jia,Jeremiah Kim,Aaron Palmer Esser-Kahn,Peter Deak

Journal

Frontiers in Medicine

Published Date

2024/1/5

Introduction Tolerogenic Dendritic Cells (tolDCs) have an exceptional promise as a potential therapy for autoimmune disease and transplantation rejection. TolDCs are a unique phenotype of antigen presenting cells (APCs) that can influence naïve T cells into antigen specific T regulatory cells (Tregs), which can re-establish tolerance against auto/allo-antigens in the long term. Despite their promise, tolDCs have not found clinical success. Most strategies seek to generate tolDCs ex vivo by differentiating naïve dendritic cells (DCs) with immunosuppressive agents. Recently, we developed a tolDC generation strategy, which we call Push/Pull Immunomodulation (PPI). In PPI, DCs are treated with combinations of toll-like-receptor (TLR) agonists and immunomodulatory agents, which generate more robust, Treg-inducing tolDCs than previous strategies. Here, we seek to identify more potent and clinically viable PPI formulations using data from a high-throughput screening project. Methods Over 40,000 combinations of pathogen-associated molecular patterns (PAMPs) and immunomodulatory small molecules were screened using a modified murine macrophage line, RAW dual cells, to observe the effect of these combinations on two major immune regulatory transcription factors, NF-κB and IRF. Combinations were further screened for inflammatory cytokine activity using a human monocyte cell line, THP-1, then on murine DCs. Leading candidates were co-cultured with T cells to assess antigen specific T cell responses. Results From this data, we identified 355 combinations that showed low or moderate IRF activity, low NF-κB activity, low …

Patterned polymer manufacturing by laser-ignited multi-initiation-point frontal polymerization

Authors

Andrés Cook,Mason Dearborn,Trevor Anderberg,Kavya Vaidya,Justin Jureller,Aaron Esser-Kahn,Allison Squires

Journal

Bulletin of the American Physical Society

Published Date

2024/3/4

We present laser-patterned photothermal heating as a new means to simultaneously initiate self-propagating polymerization reactions at multiple locations in a 2-D sample. While frontal polymerization (FP) is well established for rapid polymerization of thermoset plastics using only a small point input of heat rather than a kiln, until now FP initiated at more than two points simultaneously has not been demonstrated. We incorporated carbon black (CB) particles into liquid resin (dicyclopentadiene; DCPD) to enhance absorption of energy from a rapidly scanned Ti: Sapph laser (800nm) focused on a shallow and broad sample (3 mm x 10 cm; dxw). We demonstrate successful multipoint polymerization at up to seven sites and in various geometries and show that initiation in DCPD+ CB requires an approximately fixed energy input at high powers where thermal diffusion can be neglected. We also present a theoretical …

β-glucan induced trained immunity enhances antibody levels in a vaccination model in mice

Authors

Jainu Ajit,Qing Chen,Trevor Ung,Matthew G Rosenberger,Jeremiah Kim,Ani Solanki,Jingjing Shen,Aaron P Esser-Kahn

Journal

bioRxiv

Published Date

2024

Trained immunity improves disease resistance by strengthening our first line of defense, the innate immune system. Innate immune cells, predominantly macrophages, are epigenetically and metabolically rewired by β-glucan, a fungal cell wall component, to induce trained immunity. These trained macrophages exhibit increased co-stimulatory marker expression and altered cytokine production. Signaling changes from antigen-presenting cells, including macrophages, polarize T-cell responses. Recent work has shown that trained immunity can generally enhance protection against infection, and some work has shown increased protection with specific vaccines. It has been hypothesized that the trained cells themselves potentially modulate adaptive immunity in the context of vaccines. However, the mechanistic link between trained immunity on subsequent vaccinations to enhance antibody levels has not yet been identified. We report that trained immunity induced by a single dose of β-glucan increased antigen presentation in bone-marrow-derived macrophages (BMDMs) and CD4+ T cell proliferation in-vitro. Mice trained with a single dose of β-glucan a week before vaccination elicited higher antigen-specific antibody levels than untrained mice. Further experiments validate that macrophages mediate this increase. This effect persisted even after vaccinations with 100 times less antigen in trained mice. We report β-glucan training as a novel prophylactic method to enhance the effect of subsequent vaccines.

Immune Potentiation of PLGA Controlled-Release Vaccines for Improved Immunological Outcomes

Authors

Britteny J Cassaidy,Brittany A Moser,Ani Solanki,Qing Chen,Jingjing Shen,Kristen Gotsis,Zoe Lockhart,Nakisha Rutledge,Matthew G Rosenberger,Yixiao Dong,Delaney Davis,Aaron P Esser-Kahn

Journal

ACS Omega

Published Date

2024/2/28

With the emergence of SARS-CoV-2 and the continued emergence of new infectious diseases, there is a need to improve and expand current vaccine technology. Controlled-release subunit vaccines provide several benefits over current vaccines on the market, including the use of less antigen and fewer boost doses. Previously, our group reported molecules that alter NF-κB signaling improved the vaccine’s performance and improved adjuvant-related tolerability. In this report, we test how these immune potentiators will influence responses when included as part of a controlled-release poly(lactic-co-glycolic) vaccine formulation. Murine in vivo studies revealed that SN50 and honokiol improved antibody levels at early vaccine time points. Microparticles with SN50 produced strong antibody levels over a longer period compared to microparticles without SN50. The same particles also increased T-cell activity. All of the …

Nanovaccine that activates the NLRP3 inflammasome enhances tumor specific activation of anti-cancer immunity

Authors

Saikat Manna,Sampa Maiti,Jingjing Shen,Adam Weiss,Elizabeth Mulder,Wenjun Du,Aaron P Esser-Kahn

Journal

Biomaterials

Published Date

2023/5/1

Neoantigen cancer vaccines that target tumor specific mutations are emerging as a promising modality for cancer immunotherapy. To date, various approaches have been adopted to enhance efficacy of these therapies, but the low immunogenicity of neoantigens has hindered clinical application. To address this challenge, we developed a polymeric nanovaccine platform that activates the NLRP3 inflammasome, a key immunological signaling pathway in pathogen recognition and clearance. The nanovaccine is comprised of a poly (orthoester) scaffold engrafted with a small-molecule TLR7/8 agonist and an endosomal escape peptide that facilitates lysosomal rupture and NLRP3 inflammasome activation. Upon solvent transfer, the polymer self-assembles with neoantigens to form ∼50 nm nanoparticles that facilitate co-delivery to antigen-presenting cells. This polymeric activator of the inflammasome (PAI) was …

Mechanically adaptive materials

Published Date

2023/9/7

Provided are mechanically adaptive materials that include a composite gel that is responsive to input energy. In some embodiments, input vibrational energy results in strengthening the composite gel. The strengthening may be reversible or irreversible according to various embodiments. In some embodiments, input vibrational energy generates chemical promotors for cross-linking reactions and/or linear polymerization via mechano-chemical transducers. In some embodiments, an applied shear stress is used to control charge generation and generate chemical promoters for cross-linking and/or linear polymerization. In some embodiments, the composite gels include a polymer network and/or polymer network precursors, reactive groups and/or linkers formed by reaction of the reactive groups, and a mechano-chemical transducer. Also provided are methods of mechanically promoted synthesis of polymers and …

Immunomodulators identified via high-throughput screening enhance control of vaccine adjuvanticity

Authors

Matthew Glenn Rosenberger,Jeremiah Kim,Aaron Esser-Kahn

Journal

The Journal of Immunology

Published Date

2023/5/1

Stimulation of the innate immune system is crucial in both vaccinations and immunotherapies. This is often achieved through adjuvants, molecules that usually activate pattern recognition receptors (PRRs) and stimulate two innate immune signaling pathways: the nuclear factor kappa-light-chain-enhancer of activated B-cells pathway (NF-κB) and the interferon regulatory factors pathway (IRF). Engineering the immune response via fine control of these pathways, however, is quite difficult. We demonstrate the ability to alter and improve adjuvant activity via the addition of small molecule “immunomodulators” to existing PRR agonists. By modulating signaling activity instead of receptor binding, these molecules allow the customization of select innate responses. We demonstrate both inhibition and enhancement of the products of the NF-κB and IRF pathways by several orders of magnitude. Some modulators apply …

Toll-like receptor agonist formulations and methods of use

Published Date

2023/3/9

Aspects of the disclosure relate to nanoparticle formulations and methods for generating nanoparticles. Embodiments include nanoparticles comprising an amphiphile and a polymer co-assembly agent. In some cases, polymers for use in therapeutic delivery are described. In some embodiments, the disclosed methods and compositions involve TLR agonists and formulations thereof capable of activating an immune response. Certain aspects relate to nanoparticles comprising linked TLR agonists for use in immunotherapy.

Innate Immune Memory for Improved Vaccine Response

Authors

Aaron P Esser-Kahn

Journal

The Journal of Immunology

Published Date

2023/5/1

Emerging diseases require generating new vaccines, which can often be time-consuming. An alternate method to boost host defense is by inducing nonspecific innate immune memory, called trained immunity, to develop novel prophylactics. Many molecules, most notably β-glucan, induce trained immunity, but their effects are often short-lived and uncontrolled. This lack of temporal control limits both the therapeutic ability of training and provides fundamental questions about its nature. To improve on the capabilities of β-glucan, we developed a method for temporal control of trained immunity and examined its use both as a prophylactic and as an additive for improve vaccine outcomes. We engineered controlled release nanoparticles encapsulating only 3.5% the standard dose of β-glucan to attain sustained release over a month. Nanoparticle trained mice exhibited prolonged training effects and improved …

Cell-targeted vaccines: implications for adaptive immunity

Authors

Trevor Ung,Nakisha S Rutledge,Adam M Weiss,Aaron P Esser-Kahn,Peter Deak

Published Date

2023/8/16

Recent advancements in immunology and chemistry have facilitated advancements in targeted vaccine technology. Targeting specific cell types, tissue locations, or receptors can allow for modulation of the adaptive immune response to vaccines. This review provides an overview of cellular targets of vaccines, suggests methods of targeting and downstream effects on immune responses, and summarizes general trends in the literature. Understanding the relationships between vaccine targets and subsequent adaptive immune responses is critical for effective vaccine design. This knowledge could facilitate design of more effective, disease-specialized vaccines.

Bioinspired mechanical mineralization of organogels

Authors

Jorge Ayarza,Jun Wang,Hojin Kim,Pin-Ruei Huang,Britteny Cassaidy,Gangbin Yan,Chong Liu,Heinrich M Jaeger,Stuart J Rowan,Aaron P Esser-Kahn

Journal

Nature Communications

Published Date

2023/12/14

Mineralization is a long-lasting method commonly used by biological materials to selectively strengthen in response to site specific mechanical stress. Achieving a similar form of toughening in synthetic polymer composites remains challenging. In previous work, we developed methods to promote chemical reactions via the piezoelectrochemical effect with mechanical responses of inorganic, ZnO nanoparticles. Herein, we report a distinct example of a mechanically-mediated reaction in which the spherical ZnO nanoparticles react themselves leading to the formation of microrods composed of a Zn/S mineral inside an organogel. The microrods can be used to selectively create mineral deposits within the material resulting in the strengthening of the overall resulting composite.

Discovery of new states of immunomodulation for vaccine adjuvants via high throughput screening: expanding innate responses to PRRs

Authors

Jeremiah Y Kim,Matthew G Rosenberger,Siquan Chen,Carman Km Ip,Azadeh Bahmani,Qing Chen,Jinjing Shen,Yifeng Tang,Andrew Wang,Emma Kenna,Minjun Son,Savas Tay,Andrew L Ferguson,Aaron P Esser-Kahn

Journal

ACS Central Science

Published Date

2023/2/23

Stimulation of the innate immune system is crucial in both effective vaccinations and immunotherapies. This is often achieved through adjuvants, molecules that usually activate pattern recognition receptors (PRRs) and stimulate two innate immune signaling pathways: the nuclear factor kappa-light-chain-enhancer of activated B-cells pathway (NF-κB) and the interferon regulatory factors pathway (IRF). Here, we demonstrate the ability to alter and improve adjuvant activity via the addition of small molecule “immunomodulators”. By modulating signaling activity instead of receptor binding, these molecules allow the customization of select innate responses. We demonstrate both inhibition and enhancement of the products of the NF-κB and IRF pathways by several orders of magnitude. Some modulators apply generally across many receptors, while others focus specifically on individual receptors. Modulators boost …

Modulating Innate Immune Responses for Improved Vaccine Tolerability and Durability

Authors

Aaron P Esser-Kahn,Matthew Glenn Rosenberger,Jeremiah Kim

Journal

The Journal of Immunology

Published Date

2023/5/1

Stimulation of the innate immune system is crucial in both effective vaccinations and immunotherapies. This is often achieved through adjuvants, molecules that usually activate pattern recognition receptors (PRRs) and stimulate two innate immune signaling pathways: the nuclear factor kappa-light-chain-enhancer of activated B-cells pathway (NF-κB) and the interferon regulatory factors pathway (IRF). Here, we demonstrate the ability to alter and improve adjuvant activity viathe addition of small molecule “immunomodulators”. By modulating signaling activity instead of receptor binding, these molecules allow the customization of select innate responses. We demonstrate both inhibition and enhancement of the products of the NF-κB and IRF pathways by several orders of magnitude. Some modulators apply generally across many receptors, while others focus specifically on individual receptors. Modulators boost …

Stress-activated friction in sheared suspensions probed with piezoelectric nanoparticles

Authors

Hojin Kim,Aaron P Esser-Kahn,Stuart J Rowan,Heinrich M Jaeger

Journal

Proceedings of the National Academy of Sciences

Published Date

2023/12/5

A hallmark of concentrated suspensions is non-Newtonian behavior, whereby the viscosity increases dramatically once a characteristic shear rate or stress is exceeded. Such strong shear thickening is thought to originate from a network of frictional particle–particle contact forces, which forms under sufficiently large stress, evolves dynamically, and adapts to changing loads. While there is much evidence from simulations for the emergence of this network during shear thickening, experimental confirmation has been difficult. Here, we use suspensions of piezoelectric nanoparticles and exploit the strong local stress focusing within the network to activate charge generation. This charging can then be detected in the measured ac conductance and serve as a signature of frictional contact formation. The direct link between stress-activated frictional particle interactions and piezoelectric suspension response is further …

Engineering Spin Coherence in Core-Shell Diamond Nanocrystals

Authors

Uri Zvi,Denis R Candido,Adam Weiss,Aidan R Jones,Lingjie Chen,Iryna Golovina,Xiaofei Yu,Stella Wang,Dmitri V Talapin,Michael E Flatté,Aaron P Esser-Kahn,Peter C Maurer

Journal

arXiv preprint arXiv:2305.03075

Published Date

2023/5/4

Diamond nanocrystals can harbor spin qubit sensors capable of probing the physical properties of biological systems with nanoscale spatial resolution. These diamond nanosensors can readily be delivered into intact cells and even living organisms. However, applications beyond current proof-of-principle experiments require a substantial increase in sensitivity, which is generally limited by surface-noise-induced spin dephasing and relaxation. In this work, we significantly reduce magnetic surface noise by engineering core-shell structures, which in combination with dynamical decoupling result in qubit coherence times (T2) ranging from 52us to 87us - a drastic improvement over the 1.1us to 35us seen in bare particles. This improvement in spin coherence, combined with an overall increase in particle fluorescence, corresponds to a two-order-of-magnitude reduction in integration time. Probing qubit dynamics at a single particle level, furthermore, reveals that the noise characteristics fundamentally change from a bath with spins that rearrange their spatial configuration during the course of an experiment to a more dilute static bath. The observed results shed light on the underlying mechanisms governing spin dephasing in diamond nanocrystals and offer an effective noise mitigation strategy based on engineered core-shell structures.

See List of Professors in Aaron Esser-Kahn University(University of Chicago)

Aaron Esser-Kahn FAQs

What is Aaron Esser-Kahn's h-index at University of Chicago?

The h-index of Aaron Esser-Kahn has been 24 since 2020 and 28 in total.

What are Aaron Esser-Kahn's top articles?

The articles with the titles of

Novel non-immunogenic trained immunity inducing small molecule with improved anti-tumor properties

Polymer Patterning by Laser-Induced Multipoint Initiation of Frontal Polymerization

An anti-Brownian magnetic feedback trap for bio-orthogonal manipulation of nanoparticles

Evidence of collective influence in innate sensing using fluidic force microscopy

Protocol for localized macrophage stimulation with small-molecule TLR agonist via fluidic force microscopy

High-throughput screening identification of novel immunomodulatory combinations for the generation of tolerogenic dendritic cells

Patterned polymer manufacturing by laser-ignited multi-initiation-point frontal polymerization

β-glucan induced trained immunity enhances antibody levels in a vaccination model in mice

...

are the top articles of Aaron Esser-Kahn at University of Chicago.

What are Aaron Esser-Kahn's research interests?

The research interests of Aaron Esser-Kahn are: immuno-engineering, vaccines, chemistry, polymer science, adaptive materials

What is Aaron Esser-Kahn's total number of citations?

Aaron Esser-Kahn has 4,266 citations in total.

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