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Otolaryngology and Communication Sciences

Pepsin and Reflux Laboratory

Dr. Johnston's research laboratory aims to develop new treatments for reflux, which specifically target pepsin.
To contact Dr. Johnson, please email njohnston@mcw.edu.
Learn More about Dr. Johnston
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Pepsin and reflux lab members.

Members of the pepsin reflux laboratory.

Members of the pepsin reflux laboratory.

Pepsin and reflex lab members at an event.

Development of Pepsin Inhibitors as a Novel Therapeutic Approach for Reflux Disease: Recent and Ongoing Research

Oral fosamprenavir for the treatment of laryngopharyngeal reflux (LPR)

Preclinical Studies

Preclinical Studies

Laboratory-based investigation of the efficacy and cell and molecular protective effects of fosamprenavir and its prodrug, amprenavir, in models of the human aerodigestive tract.

In vivo efficacy study of fosamprenavir in an LPR mouse model

  • Johnston N, Samuels TL, Goetz CJ, Arnold LA, Smith BC, Seabloom D, Wuertz B, Ondrey F, Wiedmann TS, Vuksanovic N, Silvaggi NR, MacKinnon AC, Miller J, Bock J, Blumin JH. Oral and Inhaled Fosamprenavir Reverses Pepsin-Induced Damage in a Laryngopharyngeal Reflux Mouse Model. Laryngoscope. 2023 Jan;133 Suppl 1(Suppl 1):S1-S11. doi: 10.1002/lary.30242. Epub 2022 Jun 9. PMID: 35678265; PMCID: PMC9732152.

Protection against epithelial barrier disruption and downstream cancer-associated effects of weakly acidified pepsin in an in vitro model

  • Samuels TL, Blaine-Sauer S, Yan K, Johnston N. Amprenavir inhibits pepsin-mediated laryngeal epithelial disruption and E-cadherin cleavage in vitro. Laryngoscope Investig Otolaryngol. 2023 Jun 22;8(4):953-962. doi: 10.1002/lio2.1102. PMID: 37621274; PMCID: PMC10446255.
Clinical Trials

Clinical Trials

Evaluation of a repurposing strategy, using FDA-approved HIV-1 protease inhibitor, fosamprenavir (commercial tablets) for symptoms of LPR.

  • Phase II Proof of Concept Study: A 12-Week Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Assess the Efficacy of Oral Fosamprenavir for Laryngopharyngeal Reflux.

Oral fosamprenavir sodium alginate for PPI refractory gastroesophageal reflux disease (GERD)

Preclinical Studies

Preclinical Studies

Protection against epithelial barrier disruption and downstream cancer-associated effects of weakly acidified pepsin encountered during proton pump inhibitor (PPI) recalcitrant GERD

  • Blaine-Sauer S, Samuels TL, Yan K, Johnston N. The Protease Inhibitor Amprenavir Protects against Pepsin-Induced Esophageal Epithelial Barrier Disruption and Cancer-Associated Changes. Int J Mol Sci. 2023 Apr 5;24(7):6765. doi: 10.3390/ijms24076765. PMID: 37047737; PMCID: PMC10095080.

Protection against global transcriptomic changes caused by weakly acidified pepsin mimicking PPI-recalcitrant GERD

  • Ergun P, Samuels TL, Mathison AJ, Liu T, Jin VX, Johnston N. Amprenavir Mitigates Pepsin-Induced Transcriptomic Changes in Normal and Precancerous Esophageal Cells. Int J Mol Sci. 2025 Jun 26;26(13):6182. doi: 10.3390/ijms26136182. PMID: 40649959; PMCID: PMC12250232.

Esophageal mucoadhesion and conversion of a novel fosamprenavir-sodium alginate formulation in an ex vivo porcine model (study underway)

Clinical Trial

Clinical Trial

Evaluation of the efficacy of a novel fosamprenavir-sodium alginate formulation designed for superior esophageal mucoadhesion and local esophageal delivery.

  • Phase II Proof of Concept Study: Randomized, Double-blind, Placebo-Controlled

    Trial of Fosamprenavir-Sodium Alginate Administered Orally for 8 Weeks to Patients with Proton Pump Inhibitor Refractory Gastroesophageal Reflux Disease. Estimated Start: Sept 2026

Fosamprenavir Dry Powder Inhaler for LPR

Preclinical Studies

Preclinical Studies

Laboratory-based investigation of cell and molecular protective effects of fosamprenavir and its prodrug, amprenavir, in models of the human aerodigestive tract.

In vivo efficacy study of inhaled fosamprenavir in an LPR mouse model

  • Johnston N, Samuels TL, Goetz CJ, Arnold LA, Smith BC, Seabloom D, Wuertz B, Ondrey F, Wiedmann TS, Vuksanovic N, Silvaggi NR, MacKinnon AC, Miller J, Bock J, Blumin JH. Oral and Inhaled Fosamprenavir Reverses Pepsin-Induced Damage in a Laryngopharyngeal Reflux Mouse Model. Laryngoscope. 2023 Jan;133 Suppl 1(Suppl 1):S1-S11. doi: 10.1002/lary.30242. Epub 2022 Jun 9. PMID: 35678265; PMCID: PMC9732152.

Pre-GLP safety testing of inhaled fosamprenavir and design of a laryngopharyngeal dry powder inhaler

  • Lesnick A, Samuels TL, Seabloom D, Wuertz B, Ojha A, Seelig D, Ondrey F, Wiedmann TS, Hogan C, Torii E, Ouyang H, Yan K, Garcia GJM, Bock JM, Johnston N. Inhaled fosamprenavir for laryngopharyngeal reflux: Toxicology and fluid dynamics modeling. Laryngoscope Investig Otolaryngol. 2024 Jan 24;9(1):e1219. doi: 10.1002/lio2.1219. PMID: 38362183; PMCID: PMC10866582.
  • Dey S, Jadcherla A, Johnston N, Bock JM, Garcia GJM. Optimizing dry powder inhaler for laryngopharyngeal reflux: Effects of particle size and breathing technique. Journal of Aerosol Science 2025 189, 106641.

GLP toxicologic assessment (to be completed late 2025)

Clinical Trials

Clinical Trials

Evaluation of the safety and efficacy a novel inhaled fosamprenavir formulation that offers targeted laryngopharyngeal delivery for reduced dosing.

  • Phase I Safety/Efficacy Study

Drug Development Timeline

Drug Development Timeline

Informational Videos

New Approach to Reflux Treatment Could Revolutionize Care for LPR and GERD Header

Dr. Johnston’s research has uncovered a crucial culprit in reflux disease: pepsin, a digestive enzyme produced in the stomach.

Wisconsin's Afternoon News w/ John Mercure & Julia Fello - June 24th, 2025

Presenter: Nikki Johnston, PhD

 

European Union of Phonetricians Congress Presentation 2023
Presenter: Tina Samuels, PhD

Taiwan Voice Society Annual Meeting in conjunction with International Voice Symposium of TCVGH September 2022
Presenter: Nikki Johnston, PhD

Learn more about Dr. Johnston and her team's research accomplishments. 

OTO Research Team at Gala
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Grants Awards and Funding

Recent Awards:

Title: Inhaled Fosamprenavir for the Treatment of Laryngopharyngeal Reflux (LPR)
Source: Falk Medical Trust Transformational Award
Category: Investigator Initiated Study
Dates: 11/30/2022 - 11/30/2023

Title: Investigation into the mechanisms by which topical alginates preserve esophageal epithelial barrier function during pepsin-acid insult.
Source: Reckitt Benckiser Health Limited
Category: Investigator Initiated Translational Research Grant
Dates: 01/01/23 – 12/31/23

Title: Preparation for clinical trial of fosamprenavir
Source: N-Zyme Biomedical Inc.
Category: Industry Sponsored Grant
Dates: 01/01/2023 – 31/12/2023

Research Interests
  • Extraesophageal reflux
  • Use of pepsin as a marker for extraesophageal reflux
  • Uptake of pepsin by laryngeal epithelial cells & its role in reflux - attributed laryngeal injury & disease
  • Isolate and identification of the receptor with which pepsin interacts on laryngeal epithelial cells
  • New therapeutics for reflux (pepsin inhibitors/receptor antagonists)
  • Role of reflux, specifically pepsin, in laryngopharyngeal cancers
  • Role of pepsin in Barrett’s esophagus and esophageal adenocarcinoma
Society Memberships
  • American Association for Cancer Research
  • Society for Bimolecular Sciences
  • Association for Research in Otolaryngology
  • American Broncho-Esophagological Association
  • Medical College of Wisconsin Cancer Center
  • Clinical and Translational Science Institute of Southeast Wisconsin
  • OESO-Stanford SEMPIRE Multidisciplinary Platform of Esophagology Pilot Center
  • Membership of the World Organization for Specialized Studies on Diseases of the Esophagus (OESO) and our team are an OESO Stanford Esophageal Multidisciplinary Program in Innovative Research Excellence (OESO-SEMPIRE) Pilot Center of Excellence

Current Laboratory and Study Team Members

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Jonathan Bock, MD

Professor

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Joel H. Blumin, MD

Chief, Professor

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Pelin Ergun, PhD

Postdoctoral Researcher

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Nikki Johnston, PhD

Professor, Otolaryngology & Communication Sciences and Microbiology & Immunology

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Ally Lesnick

Research Coordinator

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Karolina Lungova

Medical Student

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Tina Samuels, MS

Program Manager, Airway, Digestive, & Voice Research

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Mark A. Vukovich, MSN, APNP

Nurse Practitioner

Recent Publications

Publications of Nikki Johnston PhD from the Faculty Collaboration Database

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