Laboratory of Fumito Ichinose, MD, PhD

Overview

The Ichinose Laboratory studies how nitric oxide, hydrogen sulfide, hypoxia, and mitochondrial biology regulate responses to injury, aging, and disease. Using molecular, translational, and preclinical approaches, we seek to develop new therapies for critical illness, cardiopulmonary disorders, neurodegeneration including Parkinson’s disease, and resuscitation-related organ injury.

Research Projects

Sulfide Oxidation and Brain Health

Sulfide is now recognized not only as a signaling molecule but also as an important regulator of mitochondrial function, and its oxidation is essential for maintaining energy balance in the brain. We study how disruption of this pathway contributes to neurodegeneration, impaired bioenergetics, and neuronal vulnerability during aging and disease. A major goal of our work is to define the role of sulfide oxidation in neurodegenerative disorders such as Parkinson’s disease, amyotrophic lateral sclerosis (ALS), as well as mitochondrial diseases including Leigh syndrome and Friedreich’s ataxia.

To address these questions, we use molecular, biochemical, and preclinical approaches to examine how enzymes involved in sulfide catabolism influence brain function under normal and pathological conditions. We also test whether restoring sulfide oxidation capacity or supplementing protective sulfide-derived species such as persulfides can preserve neuronal survival and improve functional outcomes. By linking fundamental mitochondrial biology to translational models of brain disease, our work aims to identify new therapeutic strategies to protect the brain and promote long-term neurological health.

Hypoxia as a Therapy for Neurodegenerative Diseases

Our hypoxia therapy research explores whether carefully controlled reductions in inspired oxygen can activate adaptive pathways that protect tissues, improve mitochondrial function, and enhance resilience to disease. We study how mild to moderate hypoxia influences metabolism, redox signaling, inflammation, and cellular stress responses, with the goal of harnessing these endogenous protective mechanisms for therapy. By defining the biological effects of intermittent and sustained hypoxic exposure in clinically relevant models, we aim to identify practical and safe strategies for therapeutic hypoxia.

A major focus of this work is Parkinson’s disease, where we investigate whether hypoxia can improve motor function, preserve dopaminergic neurons, and slow neurodegenerative progression. We combine mechanistic studies with preclinical testing to determine how hypoxia affects mitochondrial function, oxidative stress, and neuronal survival in models of Parkinson’s disease and related movement disorders. More broadly, our goal is to build a strong scientific foundation for translating hypoxia-based interventions into feasible therapies for neurodegeneration and other chronic diseases.

Role of Sedation in Critical Illness and Aging

Sedation is a routine part of post-arrest critical care, yet its biological effects during this vulnerable period remain poorly understood. We study how commonly used sedatives shape neurological and systemic outcomes after cardiac arrest, with the goal of identifying strategies that not only provide comfort and ventilator tolerance but also improve recovery and survival.

Beyond cardiac arrest, we investigate how sedation affects organ function, metabolism, sleep-related pathways, and long-term outcomes in critical illness, age-dependent cognitive decline, and biological aging. By combining mechanistic studies with translational models, we seek to understand when sedation is protective, when it may be harmful, and how its timing, depth, and drug class can be optimized. This work aims to guide more precise and biology-informed use of sedation across a wide range of acute and critical care settings, as well as for healthy aging and long-term space travel.

Research Team

Fumito Ichinose, MD PhD
Professor of Anesthesiology, Massachusetts General Hospital and Harvard Medical School

Luca Zazzeron, MD
Instructor in Anaesthesia, Massachusetts General Hospital and Harvard Medical School

Luca Zazzeron, MD, studies pulmonary development and pulmonary vascular adaptation in mouse models of high-altitude hypoxia. His work examines the therapeutic potential of inhaled nitric oxide for hypoxia-induced pulmonary hypertension and impaired cardiopulmonary development, and also explores carbon monoxide phototherapy as a novel treatment for carbon monoxide poisoning.

Eizo Marutani, MD PhD
Investigator in Instruction, Massachusetts General Hospital and Harvard Medical School

Eizo Marutani, MD, PhD is a physician-scientist whose research focuses on mitochondrial biology, sulfide metabolism, and hypoxia-based therapies in neurodegenerative disease. His work investigates how hypoxia and sulfide catabolism influence neuronal survival, mitochondrial function, and disease progression, with a particular emphasis on Parkinson’s disease and the development of new translational therapies.

Kakeru Shimoda, MD, PhD
Research Fellow, Massachusetts General Hospital

Kakeru Shimoda, MD, PhD investigates how sulfide metabolism and mitochondrial dysfunction contribute to neurodegeneration. His work focuses on developing translational therapeutic strategies to preserve neuronal function and prevent disease progression.

Yuki Sugimoto, MD PhD
Research Fellow, Massachusetts General Hospital

Yuki Sugimoto, MD, PhD investigates the effects of sedation on recovery after cardiac arrest, aging, and shallow hibernation–like states. His work aims to understand how sedation influences brain function, metabolism, and organ protection in order to develop improved translational strategies for critical care and beyond.

Publications

View publications

Selected Publications

• Marutani E, Miranda M, Durham TJ, Kim SH, Russell DL, Wiesenthal PP, Lichtenegger P, Menard MA, Brzozowski CF, Li H, Ruvkun G, Meisel JD, Volpicelli-Daley L, Mootha VK, Ichinose F. Hypoxia ameliorates neurodegeneration and movement disorder in a mouse model of Parkinson's disease. Nat Neurosci. 2025 Sep;28(9):1858-1867. doi: 10.1038/s41593-025-02010-4. Epub 2025 Aug 6. PubMed PMID: 40770507; PubMed Central PMCID: PMC12411263.
• Zazzeron L, Mereto E, Lichtenegger P, Moore E, Tattersfield H, Marutani E, Yu B, Berra L, Bloch DB, Ichinose F. Effects of continuous low-dose nitric oxide in a murine model of pulmonary hypertension with impaired lung development. Anesthesiology. 2026 Jan 16;. doi: 10.1097/ALN.0000000000005939. [Epub ahead of print] PubMed PMID: 41544222.
• Yu B, Safaee Fakhr B, Bry L, Shih A, Wanderley HV, Dai Y, Carroll RW, Winterton D, Buehl T, Okda M, Bruno G, Marutani E, Cenci S, Medeiros KJ, Villalobos R, Spina S, Mietto C, Bittner EA, Cereda M, Delaney ML, Cadringher P, LaVita C, Stuehr DJ, Arora P, Ichinose F, Berra L. Inhaled nitric oxide at 300 ppm treats multidrug-resistant Pseudomonas pneumonia in swine and is safe in humans. Sci Transl Med. 2026 Jan 21;18(833):eady2646. doi: 10.1126/scitranslmed.ady2646. Epub 2026 Jan 21. PubMed PMID: 41564156.
• Kanemaru E, Shimoda K, Marutani E, Morita M, Miranda M, Miyazaki Y, Sinow C, Sharma R, Dong F, Bloch DB, Akaike T, Ichinose F. Exclusion of sulfide:quinone oxidoreductase from mitochondria causes Leigh-like disease in mice by impairing sulfide metabolism. J Clin Invest. 2024 Jun 13;134(15). doi: 10.1172/JCI170994. PubMed PMID: 38870029; PubMed Central PMCID: PMC11290971.
• Marutani E, Morita M, Hirai S, Kai S, Grange RMH, Miyazaki Y, Nagashima F, Traeger L, Magliocca A, Ida T, Matsunaga T, Flicker DR, Corman B, Mori N, Yamazaki Y, Batten A, Li R, Tanaka T, Ikeda T, Nakagawa A, Atochin DN, Ihara H, Olenchock BA, Shen X, Nishida M, Hanaoka K, Kevil CG, Xian M, Bloch DB, Akaike T, Hindle AG, Motohashi H, Ichinose F. Sulfide catabolism ameliorates hypoxic brain injury. Nat Commun. 2021 May 25;12(1):3108. doi: 10.1038/s41467-021-23363-x. PubMed PMID: 34035265; PubMed Central PMCID: PMC8149856.