About

Joshua J Meeks is a Professor of Urology and an Associate Professor in Urology, Biochemistry and Molecular Genetics at Northwestern University Feinberg School of Medicine. He is affiliated with the Department of Urology and is involved in research and clinical work related to urology. His professional profile is associated with the Northwestern Medicine system, and he is part of various research institutes including the Center for Genetic Medicine, Northwestern University Clinical and Translational Sciences Institute (NUCATS), Robert H. Lurie Comprehensive Cancer Center, Simpson Querrey Institute for Epigenetics, among others. His work focuses on urology, with an emphasis on research areas such as urologic cancers, regenerative medicine, and health services and outcomes research.

Research topics

• Computational biology
• Biology
• Computer Science
• Internal medicine
• Medicine
• Environmental health
• Genetics
• Pathology
• Cancer research
• Bioinformatics

Selected publications

• Divergent Macrophage-Regulated T cell States Determine Response to Bacillus Calmette-Guérin vaccine in High-Risk Bladder Cancer

  Journal of Clinical Investigation · 2026-04-21

  articleOpen accessSenior author

  BACKGROUND: Primary therapy for high-risk bladder cancer (BCa) is repeated instillations of the tuberculosis vaccine Bacillus Calmette-Guerin (BCG). Although BCG reduces the risk of recurrence by more than half, the mechanisms underlying its immune-activating effects remain unknown. Our objective was to investigate how the immune response differs between BCG responders and non-responders and to compare systemic and local immune responses. METHODS: We performed single-cell RNA sequencing (scRNA-seq) of isolated immune cells adjacent to high-risk bladders in BCG responders and non-responders before and after BCG. We also compared concurrent scRNA-seq profiles of circulating immune cell populations with those of bladder immune cells. RESULTS: We identify an increase in Th17-like Th1 cells in BCG responders, characterized by greater expression of pro-inflammatory cytokines. Alternatively, non-responders show increased CD8+ T-cell exhaustion and T regulatory cells. We identify that the primary mechanism driving divergent T-cell activity is altered polarization and immunosuppressive signaling with myeloid cells. Using a machine-learning-based approach, we identify that Th17-like Th1 cytokines, such as IL-17, IL-21, and IL-26, are predictive of response, which is subsequently validated in a separate BCG-treated BCa cohort. CONCLUSION: Together, these findings suggest that dynamic regulation of myeloid-T cell interactions can be critical for outcomes of BCG treated bladder cancer.

  PublisherDOI

• Redefining Boundaries—Safety of Radiation Therapy in the Presence of Orthotopic Neobladder

  Advances in Radiation Oncology · 2026-04-04

  articleOpen access

  <h2>Abstract</h2><h3>Introduction</h3> Pelvic radiotherapy in patients with neobladder reconstruction following cystectomy is rare but encountered in clinical practice. Its potential impact on neobladder function remains underexplored in the current literature. <h3>Methods</h3> We conducted a retrospective study of patients with urothelial carcinoma who underwent cystectomy with neobladder reconstruction, followed by pelvic radiotherapy. Radiation dosimetric data pertaining to the neobladder was analyzed. Medical records were reviewed for evidence of urinary or neobladder dysfunction. <h3>Results</h3> Twenty-one patients were found to meet inclusion criteria at our institution and were subsequently analyzed. The median age at time of cystectomy and neobladder creation was 61 years. The mean equivalent dose in 2 Gy fractions (EQD2) using an α/β ratio of 10 of the prescribed total dose was 39.1 Gy. Three patients received multiple courses of pelvic radiotherapy, all other patients received a single course. Over half of the patients received hypofractionated radiotherapy;palliation was the most common indication. Amongst available radiation dose data, the median Dmax (defined as D0.03cc) inEQD2 using an α/β ratio of 10 to neobladder was 36.5Gy (range 5.2-98.8 Gy). The median Dmean in EQD2 using an α/β ratio of 10 to neobladder was 15.7 Gy (range 0.5-49.6 Gy). The median Dmax via EQD2 using an α/β ratio of 3 to neobladder (accounting for normal tissue effect) was 38.9 Gy (range 4.6-102.9). Although three patients experienced acute genitourinary toxicity attributable to pelvic radiotherapy, none experienced Grade 3 or worse toxicity. At median post pelvic radiotherapy follow-up duration of 13.4 months, none of the 21 patients included on this study had neobladder dysfunction that could be attributed to radiotherapy. <h3>Conclusions</h3> Pelvic radiotherapy following neobladder reconstruction post-cystectomy appears to carry minimal risk of radiation-induced neobladder toxicity. Larger studies are warranted to further validate the safety profile of pelvic radiotherapy in patients with neobladder reconstruction.

  PublisherOA PDFDOI

• STING/type I interferon pathway is required for antigen-containing PLGA nanoparticle- and apoptotic cell–induced CD4+ T cell tolerance

  Science Advances · 2026-01-02

  articleOpen access

  Autoreactive CD4 + T cell infiltration, tissue destruction, and spread epitope–specific CD4 + T cell activation underly CD4 + T cell–mediated autoimmune disease pathogenesis. Here, we identify previously unknown pathways required for antigen (Ag)–specific tolerogenic immune-modifying particle/Cour nanoparticle (TIMP/CNP)–induced tolerance. The data show that myeloid cells phagocytose CNPs, undergo apoptosis, and release oxidized DNA [8-hydroxy-2′-deoxyguanosine (8-OHG)]. Subsequently, Ag-specific CNP treatment increases the number of PD-L1 + cDC2 dendritic cells and the number of FoxP3 + , CTLA-4 + , PD-1 + , and IL-10 + regulatory CD4 + T cells via a stimulator of interferon genes (STING)/interferon-α/β receptor (IFNAR)–dependent pathway. In addition, these same pathways were found to be required for both Ag-coupled apoptotic leukocyte–induced and Ag-coupled red blood cell treatment–induced CD4 + T cell tolerance. Together, these results show that Ag-specific tolerance induced by the presence of apoptotic cells, and by CNP-induced apoptosis, requires the STING/IFNAR pathway, thereby illustrating a previously unknown function of this pathway.

  PublisherDOI

• Urothelial Cancer: What Is the Role of Expression-based Subtypes to Guide Neoadjuvant Therapy in Muscle-invasive Bladder Cancer?

  European Urology Focus · 2025-12-04 · 1 citations

  article1st authorCorresponding
  PublisherDOI

• The uTRACT registry: A single-arm, multicenter, prospective, and retrospective registry study to evaluate the real-world use of UGN-101 in participants with upper tract urothelial carcinoma (UTUC) in the United States.

  Journal of Clinical Oncology · 2025-05-28 · 2 citations

  article

  TPS4629 Background: Upper tract urothelial carcinoma (UTUC) constitutes 5–10% of primary urothelial carcinomas, affecting two in 100,000 people in the US annually. Peak incidence occurs in patients 70–90 years of age. 1-3 Low-Grade (LG) UTUC represents 40% of the total disease burden. 3 Endoscopically-guided ablation is often used to treat LG-UTUC, however recurrence is common, and the long-term surveillance risks potential complications in this elderly patient population. UGN-101 is a reverse thermal hydrogel formulation of mitomycin approved for chemoablative treatment of LG-UTUC, administered as a liquid in a chilled state, which converts to a gel depot at body temperature, resulting in a dwell time of 4–6 hours. In the phase 3 OLYMPUS trial, 42 of the 71 LG-UTUC patients treated with UGN-101 achieved complete response (CR) at 3 months. 4 Among the 41 patients followed after CR, median follow-up was 28.1 months (95% CI, 13.1-57.5), and median duration of response (DoR) was 47.8 months (95% CI, 13.0-not estimable). 5 Methods: The uTRACT registry (NCT05874921) is evaluating real-world data from patients administered UGN-101, post-FDA approval(15 Apr 2020) . Approximately 400 patients &gt;18 years old with UTUC who received ≥1 dose of UGN-101 will be enrolled at ∼20 sites. Retrospective data will be collected from patients that received UGN-101 after approval as well as prospective data from newly eligible patients. UGN-101 is administered as 6 once weekly pyelocalyceal instillations retrograde via ureteral catheter or antegrade via a nephrostomy tube. Instillation volume is based on volumetric measurements, not to exceed 15 mL (60 mg of mitomycin). For participants with a CR 3 months after the first dose, once monthly maintenance instillations may be administered ( up to 11 additional doses). Participant history and disease status are collected at baseline (prior to UGN-101 dosing), and dosing information, surveillance endoscopy and imaging results will be captured over a period of 3 years post baseline, at approximately 3, 6, 12, 24, and 36 months after the first instillation. Assessment of response will be based on endoscopic surveillance, imaging, cytology, and/or for-cause biopsy. Data analysis will be performed on the overall cohort (∼400 participants) and the LG-UTUC cohort (expected to be ∼340 participants). Outcomes collected include no evidence of disease at 3-months, DoR, recurrence free survival, time to recurrence/progression and adverse events. The uTRACT registry started enrollment in 2023 with 228 patients recruited to date. 1. Siegel RL, et al. CA Cancer J Clin. 2022;72:7-33. 2. Rouprêt M, et al. Eur Urol. 2023;84:49-64. 3. Raman J, Shore ND. Rev Urol. 2020;22:1-8. 4. Kleinmann N, et al. Lancet Oncol. 2020;21:776-785. 5. Pierorazio PM, et al. J Urol. 2024:101097ju0000000000004331. Clinical trial information: NCT05874921 .

  PublisherDOI

• Combination with BCG induction and maintenance therapy for high-risk non-muscle invasive bladder cancer

  Annals of Oncology · 2025-10-17 · 1 citations

  editorialOpen access1st authorCorresponding
  PublisherOA PDFDOI

• PD37-09 THE FIRST REPORT OF DISEASE-FREE SURVIVAL ANALYSES FROM THE NIAGARA TRIAL OF PERIOPERATIVE DURVALUMAB PLUS NEOADJUVANT CHEMOTHERAPY IN MUSCLE-INVASIVE BLADDER CANCER

  The Journal of Urology · 2025-04-08

  article1st authorCorresponding
  PublisherDOI

• STING and IFNalpha/beta receptor are required for antigen-specific apoptotic cell-induced peripheral tolerance 3152

  The Journal of Immunology · 2025-11-01

  articleOpen access

  Abstract Description Autoreactive T cell infiltration, tissue destruction, and spread epitope-specific T cell activation underly CD4+ T cell-mediated autoimmune disease pathogenesis. Antigen (Ag)-containing biodegradable poly(lactide-co-glycolide) nanoparticle, i.e. tolerogenic immune-modifying particles/Cour Nanoparticles (TIMP/CNPs), treatment is both safe and efficacious for Ag-specific tolerance induction in mice and a Phase I/IIa clinical trial for celiac disease. Here, we identify that novel pathways are required for Ag-specific CNP-induced tolerance. The data show that myeloid cells phagocytose CNPs, undergo apoptosis, and release oxidized DNA (8-OHG). Subsequently, Ag-specific CNP treatment increases FoxP3+ and IL-10+ regulatory T cells via a stimulator of interferon genes (STING)/IFN-alpha/beta receptor (IFNAR)-dependent pathway. Treatment also regulates T cells specific for the spread epitopes associated with disease progression. Furthermore, induction of apoptosis via ECDI fixation, UV irradiation, X-ray irradiation, or culture of ECDI fixed RBCs with myeloid cells induces 8-OHG expression. Treatment of mice with these apoptotic cells, or Ag-coupled RBCs induces tolerance to the associated Ag and requires the host expression of STING/IFNAR pathways. Taken together, these results are the first to show that Ag-specific tolerance induced by the presence of apoptotic cells and by CNP-induced apoptosis requires the STING/IFNAR pathway. Funding Sources This work was supported by grants to S.D.M. from Cour Pharmaceutical Development Company, NIH grant R01AI148076; and by gifts from the Johnnie Walkers MS Foundation, the Amy and David Fulton Foundation, the Crammer Family Foundation, the Thomas and Deige McLaughlin Foundation, and the Rottering Family Foundation. Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)

  PublisherOA PDFDOI

• Abstract 4103: MLL4/COMPASS dysfunction in cancer and treatment

  Cancer Research · 2025-04-21

  article

  Epigenetic status-altering mutations in chromatin-modifying enzymes are a feature of human diseases, including many cancers. We investigated cellular dependencies, or vulnerabilities, that arise when enhancer function is compromised by loss of the frequently mutated COMPASS family members MLL3 (KMT2C) and MLL4 (KMT2D). We performed a CRISPR dropout screen that revealed a targetable metabolic dependency arising from epigenetic factor deficiency, identifying potential therapies for cancers with epigenetic alterations secondary to MLL3/4-COMPASS dysfunction. We identified strong evidence that there is an internal balance between promoter and enhancer usage dictated by MLL1- versus MLL4-COMPASS, and this equilibrium is subject to disruption during cancer. Using an autochthonous carcinogen model of bladder cancer, we demonstrate that truncated, cytoplasmic MLL4 predicts response to targeted metabolic inhibition therapy for bladder cancer and could be developed as a biomarker for KMT2D-mutated cancers. We also highlight the broader potential for prognosis, patient stratification and treatment decision-making based on KMT2D mutation status in MLL4 truncation-relevant diseases, including human cancers and Kabuki Syndrome. Due to the high prevalence of loss-of-function mutations affecting MLL4 or its COMPASS partner UTX (KDM6A) in bladder cancer, we hypothesized that KMT2D mutation status may predict responsiveness to purine-targeting therapy, including methotrexate and pemetrexed. Our study found that KMT2D mutant bladder cancer cells were selectively dependent on TYMS and showed heightened sensitivity to pemetrexed, a drug that inhibits TYMS, DHFR, and GART. This suggests that targeting multiple enzymes within the one-carbon metabolism and de novo purine synthesis pathway could be promising for the treatment of MLL4/UTX-COMPASS mutant bladder cancer. Based on our previous and current findings, a clinical trial using pemetrexed in MLL4/UTX-COMPASS mutant solid tumors is being launched at Northwestern Medicine. Citation Format: Zibo Zhao, Sarah Gold, Yuki Aoi, Khyati A. Meghani, Luke St John, Rukkia Liaqat, Carolyn Moloney, Yanni Yu, Jun Qian, Issam Ben-Sahra, Rintaro Hashizume, Devalingam Mahalingam, Joshua Meeks, Ali Shilatifard. MLL4/COMPASS dysfunction in cancer and treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4103.

  PublisherDOI

• Divergent Macrophage-Regulated T cell States Determine Response to Bacillus Calmette-Guérin (BCG) in High-Risk Bladder Cancer

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-21

  preprintOpen accessSenior authorCorresponding

  Abstract The primary therapy for high-risk bladder cancer (BCa) is repeated instillations of the tuberculosis vaccine, Bacillus Calmette-Guerin (BCG). While BCG decreases the risk of recurrence by more than half, the concerted mechanisms of immune activation from BCG are unknown. Our objective was to investigate how the immune response differs between responders and non-responders to BCG therapy. We performed single-cell RNA-sequencing of isolated immune cells adjacent to high-risk bladders before and after BCG in BCG responders and non-responders. We identify an increase in Th17-like Th1 cells in BCG responders, characterized by greater expression of pro-inflammatory cytokines. Alternatively, non-responders had increased CD8+ T-cell exhaustion and T-regulatory cells. We identify that the primary mechanism of divergent T cell activity is driven by altered polarization and immunosuppressive signaling with myeloid cells. Through a machine-learning-based approach, we identified a Th17-like Th1 cytokines, such as IL17, IL21, and IL26, were predictive of a response, which were then validated in a separate BCG-treated BCa cohort. Together, this suggests that dynamic regulation of myeloid-T cell interactions can be targeted to improve BCG activity.

  PublisherDOI

Recent grants

• Epigenetic Regulation of Immune Evasion in Bladder Cancer

  NIH · 2016–2028

Frequent coauthors

• Jeff M. Michalski

  Washington University in St. Louis

  119 shared

• Noah M. Hahn

  Johns Hopkins Medicine

  85 shared

• Seth P. Lerner

  Baylor College of Medicine

  82 shared

• Thomas W. Flaig

  University of Colorado Cancer Center

  81 shared

• Jason A. Efstathiou

  Harvard University

  81 shared

• Elizabeth R. Plimack

  Fox Chase Cancer Center

  79 shared

• Terence W. Friedlander

  UCSF Helen Diller Family Comprehensive Cancer Center

  75 shared

• Harry W. Herr

  Memorial Sloan Kettering Cancer Center

  75 shared

Education

• M.D.

  Northwestern University Feinberg School of Medicine

• B.S.

  University of Illinois at Chicago