Our lab focuses on projects that have direct relevance to disorders that are regularly encountered by practicing urologists in the clinic. We are particularly interested in benign urologic disease caused by inflammation in the bladder. We have shown that nod-like receptors (NLRs) and the inflammasomes they form are present in the bladder epithelia where they serve as sensors of sterile damage and potentially bacterial infection. Upon activation, these structures mature the pro-inflammatory cytokines IL-1β and IL-18, which are released and trigger inflammation and lower urinary tract symptoms, such as increased voiding frequency.
Inflammasome formation/activation during bladder outlet obstruction (such as during benign prostatic hyperplasia or BPH) and diabetes appears to be a major contributor to urinary dysfunction in those patient populations. Consequently, these two disorders are intensely under study in our lab. A thorough understanding of the inflammasome system in the bladder, while learning to manipulate this system for therapeutic advantage, is the main pillar of our lab.
- Purves JT, Hirshman NA, Malick HA, Jin H, Harper SN, Hughes FM Jr. A possible mechanism underlying mood disorders associated with LUTS: Chronic bladder outlet obstruction causes NLRP3-dependent inflammation in the hippocampus and depressive behavior in rats. Eur Urol (submitted), 2020
- Wu J, Hayes B, Phoenix C, Macias GS, Miao Y, Hughes FM Jr, Purves JT, Reinhardt RL, Abraham SN. A Highly Polarized Th2 Bladder Response to Infection Promotes Epithelial Repair At the Expense of Preventing New Infections. Nature Immunol (in press),2020
- Hirshman NA, Hughes FM Jr, Jin H, Harrison WT, White SW, Doan I, Harper SN, Leidig PD, Purves JT. Cyclophosphamide-Induced Cystitis Results in NLRP3-Mediated Inflammation in the Hippocampus and Symptoms of Depression in Rats. Am J Physiol-Renal 1;318(2):F354-F362, Dec 2019. (PMID: 31869244) (DOI: 10.1152/ajprenal.00408.2019)
- Harper SN, Leidig PD, Hughes FM Jr, Jin H, Purves JT. Calcium Pyrophosphate and Monosodium Urate Activate the NLRP3 Inflammasome within Bladder Urothelium via Reactive Oxygen Species and TXNIP. Res Reports Urol, 11:3190325, Nov 2019. (DOI:10.2147/RRU.S225767)
- Hughes FM Jr, Hirshman NA, Inouye BM, Jin H, Stanton EW, Yun CE, Davis LG, Routh JC, Purves JT. NLRP3 Promotes Diabetic Bladder Dysfunction and Changes in Symptom-Specific Bladder Innervation. Diabetes, 68(2):430-440, Feb 2019. (PMID: 30425063) (DOI: 10.2337/db18-0845)
- Hughes FM Jr, Sexton SJ, Ledig PD, Yun CE, Jin H, Purves JT. Bladder decompensation and reduction in nerve density in a rat model of chronic bladder outlet obstruction is attenuated with the NLRP3 inhibitor glyburide. Am J Physiol-Renal, 316(1):F113-120, Jan 2019. (PMID: 30353742) (DOI: 10.1152/ajprenal.00400.2018)