About

Ashish Kulkarni is an Associate Professor and Edward S. Price Faculty Fellow in the Department of Chemical and Biomolecular Engineering at UMass Amherst. His research group works at the interface of engineering and immunobiology to develop innovative technologies aimed at achieving precise immune activation for treating diseases and improving human health. His work focuses on understanding immune system interactions in health and disease by developing ‘ImmunoEngineering’ platforms that enable the study and modulation of immune responses at spatial and temporal scales. Kulkarni's research involves engineering biologically-inspired ‘ImmunoTherapeutics’ utilizing high throughput computational platform technology, and developing ‘ImmunoTheranostic’ platforms that combine therapeutic delivery with diagnostic imaging. These technologies aim to enable real-time monitoring of immunotherapy efficacy, visualize immune responses at the cellular level, and address heterogeneity in immunotherapy responses. His multidisciplinary approach bridges nanotechnology, organic synthesis, computational chemistry, molecular imaging, mathematical modeling, and immunology to develop tools and platform technologies for fundamental and translational questions in human diseases, with the goal of creating paradigm-shifting immunotherapy strategies.

Research topics

• Cancer research
• Immunology
• Medicine
• Biology
• Chemistry
• Bioinformatics
• Biochemistry
• Internal medicine
• Materials science

Selected publications

• Logic‑gated nanomedicine activates STING to boost metastatic tumour immunotherapy

  Nature Nanotechnology · 2026-03-09

  articleSenior authorCorresponding
  PublisherDOI

• Shear-Stress Initiates Signal Two of NLRP3 Inflammasome Activation in LPS-Primed Macrophages through Piezo1

  ACS Applied Materials & Interfaces · 2025-01-21 · 10 citations

  articleOpen accessSenior authorCorresponding

  The innate immune system is tightly regulated by a complex network of chemical signals triggered by pathogens, cellular damage, and environmental stimuli. While it is well-established that changes in the extracellular environment can significantly influence the immune response to pathogens and damage-associated molecules, there remains a limited understanding of how changes in environmental stimuli specifically impact the activation of the NLRP3 inflammasome, a key component of innate immunity. Here, we demonstrated how shear stress can act as Signal 2 in the NLRP3 inflammasome activation pathway by treating LPS-primed immortalized bone marrow-derived macrophages (iBMDMs) with several physiologically relevant magnitudes of shear stress to induce inflammasome activation. We demonstrated that magnitudes of shear stress within 1.0 to 50 dyn/cm2 were able to induce ASC speck formation, while 50 dyn/cm2 was sufficient to induce significant calcium signaling, gasdermin-D cleavage, caspase-1 activity, and IL-1β secretion, all hallmarks of inflammasome activation. Utilizing NLRP3 and caspase-1 knockout iBMDMs, we demonstrated that the NLRP3 inflammasome was primarily activated as a result of shear stress exposure. Quantitative polymerase chain reaction (qPCR), ELISA, and a small molecule inhibitor study aided us in demonstrating that expression of Piezo1, NLRP3, gasdermin-D, IL-1β, and CCL2 secretion were all upregulated in iBMDMs treated with shear stress. This study provides a foundation for further understanding the interconnected pathogenesis of chronic inflammatory diseases and the ability of shear stress to play a role in their progression.

  PublisherOA PDFDOI

• Protein corona formation on supramolecular polymer nanoparticles causes differential endosomal sorting resulting in an attenuated NLRP3 inflammasome activation

  Biomaterials Science · 2025-01-01 · 1 citations

  articleSenior author

  Upon introduction into biological environments, nanoparticles undergo the spontaneous formation of a dynamic protein corona, which continually evolves and significantly modifies their physicochemical properties and interactions with biological systems. This evolving protein corona can critically impact the nanoparticles' endocytic pathways and targeting efficiency, potentially altering their functional characteristics and obscuring their intended therapeutic effects. Despite considerable focus on the characterization of corona proteins and their impact on nanoparticle uptake, the intracellular processes and their effects on immunogenicity are not yet thoroughly understood. Supramolecular polymer nanoparticles (SNPs) with a highly hydrophobic core are recognized for triggering NLRP3 inflammasome activation, a key component of the innate immune system. Here, it is reported that the protein corona formation on SNPs exerts an inhibitory effect on the activation pathway of NLRP3 inflammasome. The protein corona impairs the intrinsic capacity of SNPs to induce lysosomal membrane rupture, thereby diminishing the cellular stress signals necessary for the formation of the NLRP3 inflammasome complex. Furthermore, the cells transport SNPs with an attached protein corona to recycling endosomes, where they are sorted and prepared for exocytosis. Conversely, nascent SNPs are primarily confined to late endosomes and lysosomes, leading to lysosomal rupture and inflammasome activation. This differential routing reflects the significant impact of the protein corona on the cellular handling and subsequent biological activity of nanoparticles. In summary, this study elucidates the fundamental role of the protein corona in shaping the intracellular disposition of nanoparticles, with implications for modulating their interactions with the immune system.

  PublisherDOI

• All-inorganic CsPbI₂Br perovskite solar cells with thermal stability at 250 °C and moisture-resilience <i>via</i> polymeric protection layers

  Energy & Environmental Science · 2025-01-01 · 38 citations

  articleOpen accessCorresponding

  All-inorganic perovskites, such as CsPbI 2 Br, have emerged as promising compositions due to their enhanced thermal stability. However, they are very prone to degradation due to moisture.

  PublisherOA PDFDOI

• Engineered Immunoagonist Non‐Coding RNA (incRNA) Activates Dual TLR Pathways for Cancer Immunotherapy

  Advanced Healthcare Materials · 2025-09-04 · 1 citations

  articleSenior authorCorresponding

  Conventional mRNA therapeutics have focused on optimizing translation and minimizing immunogenicity for vaccine and protein replacement applications. However, immunogenicity, often considered a challenge, can also be harnessed for therapeutic advantage. This work challenges the necessity of extensive mRNA modification as a universal strategy by introducing 'immunoagonist non-coding RNA (incRNA)', a new class of RNA therapeutic that exploits innate immune activation rather than evading it. incRNA is produced through in vitro transcription using a non-coding plasmid DNA template without modified nucleotides or rigorous purification, leveraging the immunotherapeutic potential of single-stranded RNA (ssRNA) and double-stranded RNA (dsRNA) dual pattern recognition. Encapsulation and delivery of incRNA in lipid nanoparticles (LNPs) in vitro resulted in robust immunogenic reprogramming, including macrophage repolarization and dendritic cell maturation. These phenotypes are driven by potent dual recognition, exhibited by >20-fold induction of TLR3/interferon (dsRNA) and sixfold upregulation of TLR7/TNF-α (ssRNA) signaling. In vivo, incRNA delivery elicited innate and adaptive immune cell recruitment and significant tumor regression in a melanoma mouse model, observing further heightened immune recruitment in combination with anti-PD-1 checkpoint inhibition. Overall, incRNA demonstrates that the therapeutic efficacy of RNA therapeutics is context-dependent and can be amplified by leveraging, rather than minimizing, RNA's intrinsic immunogenicity.

  PublisherDOI

• High performance Rb2AgBiI6 perovskite solar cell with optimized charge transport layers for space applications

  Solar Energy Materials and Solar Cells · 2025-10-04 · 4 citations

  article
  PublisherDOI

• Low-Temperature Solution-Processed SnO₂ Electron Transport Layer for Stable, Lead-Free Cesium-Based Perovskite Solar Cells

  ECS Journal of Solid State Science and Technology · 2025-08-25

  article

  The electron transport layer (ETL) plays a vital role in extracting and transporting photogenerated charge carriers in a halide-based perovskite solar cells (PSCs). Tin oxide (SnO 2 ) is a promising alternative to titanium oxide (TiO 2 ) as an ETL due to its better energy level alignment with the perovskite absorber layers, high mobility, stability, and ability to be deposited at lower temperature. However, despite these advantages and extensive research on lead-free perovskite thin film solar cells, the use of SnO 2 as an ETL in all-inorganic lead-free PSCs has not been thoroughly investigated. This work presents the effect of SnO 2 as an ETL interfaced with the Cs 3 Bi 2 I 9 and CsBi 3 I 10 lead-free perovskite thin films on their structural, morphological, and photoemission spectroscopic properties. Moreover, all inorganic perovskite solar cells have been fabricated for the first time to analyze the performance in the n-i-p planar architecture with device stacks comprising ITO/SnO 2 /(Cs 3 Bi 2 I 9 or CsBi 3 I 10 )/Spiro-OMeTAD/Au. The CsBi 3 I 10 device exhibited a photo conversion efficiency (PCE) of ∼1% with a fill factor of 59% while the Cs 3 Bi 2 I 9 device showed a PCE of 0.15%. These findings mark significant progress in the eco-friendly development of lead-free Cs 3 Bi 2 I 9 and CsBi 3 I 10 perovskite-based solar cells.

  PublisherDOI

• Impact of ionizable groups in star polymer nanoparticles on NLRP3 inflammasome activation

  Biomaterials Science · 2025-01-01 · 2 citations

  articleOpen accessSenior authorCorresponding

  The advent of cancer nanovaccines (N.V.s) has transformed immunotherapy by using nanoparticles as biologic delivery vehicles or vaccine adjuvants. However, challenges remain due to nanoparticle-immune cell interactions. Investigating nanoparticle (N.P.) physicochemical effects on the innate immune system is crucial for safe biomaterials design. The NLRP3 inflammasome, a key innate immunity component, is implicated in many inflammatory disorders. Various nanoparticle-associated molecular patterns (NAMPs) trigger NLRP3 activation, but the combined effect of these NAMPs in a single N.P. platform is not well understood. Star polymer nanocarriers were chosen to study the impact of combined hydrophobic and ionizable groups on NLRP3 activation. Star polymers offer stable self-assembly, high drug/gene encapsulation, and enhanced cellular internalization. We designed 4-arm star random copolymers with constant hydrophobic moiety and varied ionizable groups to evaluate their NLRP3 activation in macrophages. The study revealed differences in cytokine release and cell death linked to ionizable groups, providing insights for selecting safe, immunomodulatory biomaterials.

  PublisherOA PDFDOI

• A novel plasmid-based co-tethered transcription platform for high yield, high purity mRNA synthesis

  Nucleic Acids Research · 2025-11-26

  articleOpen access

  This work aims to improve RNA synthesis and manufacturing, exemplified by T7 RNA polymerase-driven in vitro transcription. We developed a novel, plasmid-compatible co-tethering strategy that functionally couples RNA polymerase to its promoter DNA immobilized on a solid matrix. As demonstrated recently, co-tethering enhances promoter binding, increases RNA yield, and suppresses RNA re-binding, especially under high-salt conditions, thereby reducing double-stranded RNA by-products. The system leverages asymmetric end-labeling of linearized plasmid DNA using a simple "Klenow fill-in" reaction with modified nucleotides, enabling stable attachment of DNA to both RNA polymerase and solid support (magnetic beads). The immobilized co-tethered polymerase-DNA complex supports efficient transcription initiation in high-salt environments (which further reduces RNA re-binding), yielding RNA of high purity. Co-tethered complex remains functionally stable over extended storage and multiple transcription cycles (10-20 rounds), re-using the enzyme-DNA catalyst. Transcripts of lengths (0.8, 5.6, and 8.6 kb) are efficiently produced. Highly sensitive in vitro assays with immune cells confirm low immunogenicity and strong translational output, while in vivo validation using a novel Matrigel-plugged mouse model demonstrates robust expression and safety. With a simple modification to the DNA template, the reusable, co-tethered enzyme-DNA catalytic complex streamlines mRNA manufacturing by producing RNA of higher purity from the outset.

  PublisherDOI

• Sprayable inflammasome-inhibiting lipid nanorods in a polymeric scaffold for psoriasis therapy

  Nature Communications · 2024-10-19 · 13 citations

  articleOpen accessSenior authorCorresponding

  Localized delivery of inflammasome inhibitors in phagocytic macrophages could be promising for psoriasis treatment. The present work demonstrates the development of non-spherical lipid nanoparticles, mimicking pathogen-like shapes, consisting of an anti-inflammatory inflammasome inhibiting lipid (pyridoxine dipalmitate) as a trojan horse. The nanorods inhibit inflammasome by 3.8- and 4.5-fold compared with nanoellipses and nanospheres, respectively. Nanorods reduce apoptosis-associated speck-like protein and lysosomal rupture, restrain calcium influx, and mitochondrial reactive oxygen species. Dual inflammasome inhibitor (NLRP3/AIM-2-IN-3) loaded nanorods cause synergistic inhibition by 21.5- and 59-folds compared with nanorods and free drug, respectively alongside caspase-1 inhibition. The NLRP3/AIM-2-IN-3 nanorod when transformed into a polymeric scaffold, simultaneously and effectively inhibits RNA levels of NLRP3, AIM2, caspase-1, chemokine ligand-2, gasdermin-D, interleukin-1β, toll-like receptor 7/ 8, and IL-17A by 6.4-, 1.6-, 2.0-, 13.0-, 4.2-, 24.4-, 4.3-, and 1.82-fold, respectively in psoriatic skin in comparison to Imiquimod positive control group in an in-vivo psoriasis-like mice model. Inflammasome inhibitors have potential in psoriasis treatment. Here, the authors report on a study into the shape effects of non-spherical anti-inflammatory lipid nanoparticles made from inflammasome inhibiting lipid and demonstrate application in reducing inflammasome formation in psoriasis in vivo models.

  PublisherOA PDFDOI

Recent grants

• Biotechnology Training Program in Applied Life Sciences

  NIH · $3.2M · 2020–2030

• CAREER: Elucidating structure-function relationships of inflammasome-activating nanomaterials

  NSF · $637k · 2022–2027

• Polymeric Nanomaterials for Probing and Modulating Innate Immune Responses

  NIH · $2.0M · 2022–2027

Frequent coauthors

• Shiladitya Sengupta

  Dana-Farber Cancer Institute

  120 shared

• Aaron Goldman

  Harvard University

  73 shared

• Bhaskar Roy

  University of Alabama at Birmingham

  62 shared

• Poulomi Sengupta

  57 shared

• Ayaat Mahmoud

  50 shared

• Sudipta Basu

  Indian Institute of Technology Gandhinagar

  49 shared

• Gregory A. Wyant

  Harvard University

  48 shared

• Poornima S. Rao

  48 shared

Education

• Postdoctoral Fellow, Medicine

  Harvard Medical School

  2014

• Ph.D., Chemistry

  University of Cincinnati

  2010

Awards & honors

• NSF CAREER Award
• American Cancer Society Research Scholar Award
• Cellular and Molecular Bioengineering Young Innovator Award
• American Association for Cancer Research NextGen Star in Can…
• Cancer Research Institute Technology Impact Award