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Joseph Irudayaraj

Joseph Irudayaraj

· Founder Professor, Bioengineering (Affiliate)Verified

University of Illinois Urbana-Champaign · Bioengineering

Active 1989–2026

h-index79
Citations24.2k
Papers587145 last 5y
Funding$2.0M
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About

Joseph Irudayaraj is the Founder Professor of Bioengineering at the University of Illinois Urbana-Champaign (UIUC). He has a multidisciplinary background that combines biological engineering, biosciences, and computer sciences, which underpins his research in bioengineering. His group has extensively published in areas such as biosensors, single cell dynamics, nanotechnology applied to human health, and biosecurity. His research interests include the fabrication of sub-50 nm oxygen nanocarriers for treating ischemic diseases, oxygen delivery platforms with exosome-based therapeutics, super-resolution microscopy (STED), single molecule spectroscopy for monitoring epigenetic processes, and the toxicology of PFAS in kidney and liver cancers. Dr. Irudayaraj has held faculty positions at Purdue University, The Pennsylvania State University, and Utah State University prior to his current role. He is also involved in various professional activities, editorial roles, and service on multiple committees related to bioengineering and nanotechnology.

Research topics

  • Biology
  • Bioinformatics
  • Artificial Intelligence
  • Computer Science
  • Internal medicine
  • Cancer research
  • Chemistry
  • Medicine
  • Political Science
  • Cell biology
  • Biochemistry
  • Engineering
  • Genetics
  • Physics
  • Business
  • Risk analysis (engineering)
  • Optics
  • Biotechnology
  • Computational biology
  • Endocrinology
  • Pathology
  • Materials science
  • Biophysics
  • Anatomy

Selected publications

  • Abstract 5691: Per and polyfluoroalkyl substances (PFAS) promote proliferation and migration in genetically distinct kidney cancer cell lines

    Cancer Research · 2026-04-03

    article

    Abstract Introduction and Objectives: Per- and polyfluoroalkyl substances (PFAS) such as GenX, PFOA, and PFOS are persistent environmental pollutants increasingly associated with renal carcinogenesis. Their direct effects on kidney cancer progression remain unclear. This study investigated whether PFAS exposure enhances proliferation and migration in two genetically distinct kidney cancer models-human RCC-ER (VHL-mutant) and murine Renca (VHL-wild type). Methods: RCC-ER and Renca cells were treated with GenX, PFOA, or PFOS at physiologically relevant concentrations (0.5-40 nM). Proliferation was monitored over 72 h using the IncuCyte S3 system. Migration was assessed in ImageLock plates, where wounds were created after 24 h and imaged every 1.5 h for 72 h. Wound closure was quantified by percentage wound closure (WC) and relative wound density (RWD) using IncuCyte software. All experiments were performed in triplicate to assess dose dependency and statistical significance. Results: PFAS exposure significantly enhanced both proliferation and migration in kidney cancer cells, with compound- and cell line-specific variations. RenCa cells exhibited strong proliferative responses to GenX and PFOS from 0.5-20 nM, peaking at 5 nM respectively, while PFOA showed cytotoxic effects at these doses. In contrast, RCC-ER cells demonstrated increased proliferation in response to PFOA (max at 40 nM) and PFOS (max at 5 nM), whereas GenX had minimal effect on proliferation at low doses. All three PFAS markedly accelerated wound closure and relative wound density in both cell lines, indicating enhanced migratory potential. Collectively, these data reveal that PFAS compounds augment pro-oncogenic behaviors across human and murine kidney cancer models. Conclusion: PFAS compounds promote proliferative and migratory phenotypes in both murine and human kidney cancer models through distinct but convergent metabolic mechanisms. The conserved effects across VHL-wild-type and VHL-mutant systems underscore PFAS as a potential environmental accelerator of renal tumor progression and justify further mechanistic and translational studies. Citation Format: Rakesh Kumar Arya, Mia Sand, Sahab Ram Dewala, Can Aydogdu, Gabriela M. Diaz, Christopher Weight, Riccardo Autorino, Abhishek Chakraborty, Jacob M. Knorr, Joseph M. Irudayaraj, Laura Bukavina. Per and polyfluoroalkyl substances (PFAS) promote proliferation and migration in genetically distinct kidney cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5691.

  • Self-adjuvanting α-helical polypeptide simultaneously delivers neoantigen mRNAs and activates dendritic cells to eradicate tumors

    Proceedings of the National Academy of Sciences · 2026-04-15

    articleOpen access

    mRNA-based vaccines have demonstrated tremendous success during the era of COVID-19, but its therapeutic potential for treating cancer, especially poorly immunogenic solid tumors, remains largely underachieved. Herein, we report a class of self-adjuvanting α-helical polypeptides that can dramatically improve the antitumor efficacy of tumor neoantigen-encoding mRNAs. The α-helical polypeptides can facilitate the intracellular delivery of mRNAs into dendritic cells (DCs), simultaneously activate DCs by regulating NF-κB and IRF pathways, and improve the ability of dendritic cells to process and present mRNA-encoded neoantigens. Molecular docking and simulation results also confirm the stable complexation between mRNA and α-helical polypeptides. The conceived polyplex, upon subcutaneous administration, can migrate to the draining lymph nodes and transfect and activate DCs in the lymph nodes, resulting in superior neoantigen-specific cytotoxic T lymphocyte response in vivo. Compared to conventional lipoplexes or SM102 lipid nanoparticle-based mRNA vaccines that yield 0% tumor-free survival, the polyplex yields 83.3% and 33.3% tumor-free survival against E.G7-OVA lymphoma and 4T1 triple negative breast cancer, respectively, among the best antitumor efficacy reported to date for mRNA cancer vaccines. The polyplex also reprograms the immunosuppressive tumor microenvironment, by stimulating and enriching DCs, M1-phenotype CD86 + macrophages, and CD8 + T cells in the tumors. We also observed the upregulated expression of Programmed Death-1 (PD-1) by intratumoral CD8 + T cells and PD-L1 by 4T1 tumor cells after polyplex treatment and further demonstrated the synergistic effect between polyplex vaccine and anti-PD-1 therapy. Our polyplex system provides a facile and generalizable approach to developing robust mRNA-based cancer vaccines.

  • Exosome–niosome hybrid oxygen carrier for protection against acetaminophen-induced acute liver injury

    Biomaterials Science · 2026-01-01

    articleOpen accessSenior authorCorresponding

    . Furthermore, histological analysis revealed protective effects of ENh-OCs against centrilobular necrosis and excessive immune-infiltration. We propose that the novel oxygen nanocarrier platform introduced here might act as a protective agent against APAP-induced ALI.

  • Microbiome as a modulator of immunotherapy response in pancreatic cancer

    Cancer Plus · 2025-02-05

    articleOpen accessSenior author

    Pancreatic adenocarcinoma is widely regarded as one of the most lethal malignancies due to its rapid progression and the limited success of early detection methods and therapeutic interventions. While immunotherapy has emerged as an effective treatment option for various solid tumors, it has not demonstrated comparable efficacy in pancreatic cancer. Further research is required to evaluate the safety and efficacy of different immunotherapy modalities, including immune checkpoint inhibitors, T-cell transfer therapy, chimeric antigen receptor T-cell therapy, neoantigen vaccines, and epigenome-targeting treatments, specifically in the context of pancreatic cancer. Emerging evidence highlights the crucial role of the microbiome in modulating cancer cells’ responses to immunotherapy. Studies have increasingly implicated the gut microbiota composition as a direct influencer of tumorigenesis in pancreatic cancer. Certain microbial species have been shown to exert immunostimulatory or immunosuppressive effects on pancreatic cancer cells, thereby directly enhancing or suppressing their response to immunotherapeutic regimens. Despite these findings, there remains a paucity of comprehensive reviews on microbiome studies specific to individual immunotherapy modalities in pancreatic cancer. This review highlights the exciting potential of the microbiome in modulating pancreatic cancer responses across various immunotherapy subtypes and emphasizes the clinical need for further research in the field.

  • Oxygenating Nanobubble Hydrogel for Accelerated Surgical Wound Closure and Restoration of Native Skin Architecture

    ACS Nano · 2025-11-24 · 9 citations

    articleOpen accessSenior authorCorresponding

    Prolonged hypoxia and inflammation are critical barriers in postsurgical care, often leading to delayed healing and excessive scarring, which are complications that standard passive dressings fail to address. Here, we engineer a translationally focused oxygen-nanobubble-laden hydrogel (ONB-Gel) that actively orchestrates a phase-specific healing cascade. Composed of stable sodium alginate nanobubbles within a Carbopol matrix, the ONB-Gel provides a sustained oxygen source directly to the wound bed. In a clinically relevant rat surgical wound model, the application of ONB-Gel markedly outperformed the standard-of-care dressing (Adaptic), accelerating complete wound closure by over 25% and reducing the final scar width by more than 50%. Mechanistically, the ONB-Gel resolves tissue hypoxia, significantly downregulating inflammatory cytokines (IL-6, TNF-α), oxidative stress, and the chronic hypoxia marker. Critically, beyond accelerating closure, ONB-Gel promotes tissue regeneration, evidenced by dense, functionally aligned collagen deposition and the restoration of a near-normal epidermal architecture, unattainable with conventional dressings. Overall, ONB-Gel represents a promising platform for enhancing both the rate and the quality of postsurgical wound repair.

  • PFAS and heavy metals mixture in vitro: Insights into synergistic toxicity across multiple cell lines

    Journal of Hazardous Materials Advances · 2025-10-25 · 2 citations

    articleOpen accessSenior author
  • The urinary pathobiont <i>Actinobaculum massiliense</i> generates androgens via the <i>dirAB</i> pathway

    bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-18

    articleOpen access

    Abstract While overlooked during the Human Microbiome Project, characterizing the urinary microbiota in health and disease is a new frontier in microbiome science. Recent studies have associated differential abundance of bacterial taxa including Propionimicrobium lymphophilum and Actinobaculum / Actinotignum spp. with prostate cancer. In this study, we collected urine from subjects prior to prostate biopsy and applied a novel H uman S terolbiome D iscovery H igh-throughput (HSDH) assay to identify culturable urinary bacteria with the ability to generate androgens. Application of the HSDH assay to urine samples led to the isolation of eight P. lymphophilum strains positive for cortisol side-chain cleavage (steroid-17,20-desmolase), 17β-HSDH activity, or both. In addition, we isolated three strains of Actinobaculum massiliense that encode D HEA isomerase reductase (dir ) genes. The dirA gene encodes a novel 3β/17β-hydroxysteroid dehydrogenase/Δ 4,5 -isomerase and the dirB gene encodes a novel 17β-hydroxysteroid dehydrogenase isoform. Structural prediction and molecular dynamics reveal probable catalytic mechanisms based on the shared catalytic triad but distinct binding pocket geometries of the DirA and DirB that describe their respective reactions. Phylogenetic analysis of DirA and DirB revealed homologs in urinary tract commensals as well as bacteria associated with steroid degradation found in aquatic and terrestrial environments. Taken together, the development of the HSDH assay and the identification of the dir pathway genes is a significant advance in microbial endocrinology, laying the methodological foundation and providing the molecular basis for understanding the role of urinary tract bacteria in host endocrine physiology.

  • Visual Intelligent Loop-Mediated Isothermal Amplification Based Magnetic Bead for Rapid Detection of Burkholderia Gladioli Pv.Cocovenenans

    SSRN Electronic Journal · 2025-01-01

    preprintOpen accessSenior author
  • Synergistic toxicity of PFAS and microplastic mixtures across five human cell lines

    Environmental Pollution · 2025-10-12 · 9 citations

    articleOpen accessSenior author

    Per- and polyfluoroalkyl substances and microplastics (MPs) are ubiquitous environmental contaminants that frequently co-occur in aquatic ecosystems and human exposure pathways. While their individual toxicities have been extensively studied, the combined effects of PFAS and MP co-exposure on human health remain poorly understood. This study evaluated cytotoxic, oxidative, and genotoxic responses in five human-derived cell lines-A498 (kidney), HepG2 (liver), PC3 (prostate), A431 (skin), and A549 (lung)-following exposure to environmentally relevant concentrations of perfluorooctanoic acid (PFOA), hexafluoropropylene oxide-dimer acid (GenX), polystyrene, and low-density polyethylene, both individually and in mixtures. Our findings showed potential synergistic effects were observed primarily in kidney and liver cell lines, including increased reactive oxygen species production, elevated antioxidant gene expression, and activation of DNA repair pathways. Mixture toxicity was dependent on both dose and PFAS-to-MP ratio, with synergistic responses predominating. A498 cells consistently showed greater sensitivity than HepG2 across all toxicity endpoints, including increased ROS, antioxidant gene expression, and activation of DNA repair pathways. HepG2 cells exhibited more limited oxidative stress responses but showed significant DNA damage and H2AX upregulation in select treatments. Gene expression data suggest differential activation of redox and DNA damage response pathways between the two cell types. These findings highlight the need to incorporate mixture toxicity into risk assessments and identify oxidative stress and genotoxicity as central mechanisms of concern in PFAS and MP co-exposure.

  • Oxygenated Exosome-Based Nanoeyedrop for Mitigating Hypoxia in Corneal Wound Healing: Impact on Healing Properties of Human Corneal Epithelial Cells

    ACS Pharmacology & Translational Science · 2025-01-21 · 9 citations

    articleOpen accessSenior authorCorresponding

    The rapid and organized healing of the cornea, while maintaining optical clarity, is essential for patient health and quality of life following corneal injuries. Oxygen plays a critical role in regulating cell migration and proliferation during wound repair, and the application of stem cell-derived exosomes offers potential therapeutic benefits due to their antioxidant and antiscarring properties. In this study, we developed oxygenated exosome-coated hemoglobin nanoparticles (OExo NPs) designed for effective oxygen delivery to enhance corneal re-epithelialization, reduce inflammation, and mitigate scarring. These OExo NPs exhibit a uniform average diameter of 130 nm and demonstrate consistent oxygen release capabilities. In vitro assays using human corneal epithelial cells-transformed (HCE-T) revealed that OExo NPs significantly promote cell proliferation and accelerate migration in scratch wound assays. Fluorescence imaging confirmed the successful internalization of OExo NPs into HCE-T cells and increased intracellular oxygen levels under hypoxic conditions. Gene expression analyses indicated a downregulation of critical wound healing markers, including HIF-1α, VEGF, IL-8, and FAK, suggesting effective alleviation of hypoxia, inhibition of angiogenesis, suppression of inflammation, and reduction of scar formation. These results highlight the potential of OExo NPs as a promising therapeutic approach for topical treatment of corneal wounds.

Recent grants

Frequent coauthors

Labs

Education

  • Ph.D., Bioengineering

    University of California, Berkeley

    1998
  • M.S., Bioengineering

    University of California, Berkeley

    1995
  • B.S., Chemical Engineering

    University of Madras

    1990
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