About Fumito Ichinose, MD

Fumito Ichinose. MD
Fumito Ichinose, MD

About the Lab

The overarching research goal of the Ichinose Lab, led by Fumito Ichinose, MD, PhD as part of the Anesthesia Center for Critical Care Research, is to elucidate the molecular mechanisms responsible for the cardio-cerebral dysfunction and injury often found in patients suffering critical illness including sepsis, cardiac arrest and CPR, and neurodegenerative disorders. Objectives of our current research programs include characterization of the biological effects of NO and hydrogen sulfide (H2S) in cellular function and to develop novel therapeutic strategies.

Our Projects

Hydrogen sulfide catabolism in ischemic or hypoxic brain injury and neurodegeneration

We are investigating the role of hydrogen sulfide catabolism in ischemic or hypoxic brain injury and neurodegeneration. We use multiple animal models including hibernating 13-lined ground squirrels, murine primary cortical neurons and novel genetically modified mice models. To characterize the effects of sulfide catabolism, we developed a series of new sulfide scavengers using a database of sulfide-specific chemical probes. We also use in vivo gene transfer techniques directly into murine brains using custom-made adeno-associate virus vectors. These studies are expected to illuminate the role of sulfide catabolism not only in hypoxia tolerance and neurodegenerative diseases but also in mammalian physiology in extreme environment.

Countermeasures against H2S poisoning

Originally, H2S was discovered and studied as an environmental hazard. H2S intoxication is the second most common cause of gas-related death after carbon monoxide. Related to the first project, in this project, we seek to develop countermeasures against H2S poisoning using the newly developed library of sulfide scavengers. We will develop and examine sulfonyl azide and selenium oxide-based sulfide scavengers using established in vitro screening assays. Promising lead compounds will be tested in novel murine models of H2S intoxication and H2S-induced cardiopulmonary arrest developed in our laboratory. This project was recently funded by NIH CounterAct program.

The role of sulfide metabolism in micro-organisms

H2S is considered a gas that existed in ancient earth when life was born. Many micro-organisms retain the ability to use sulfide as an important energy source. We are investigating the role of sulfide metabolism in micro-organisms including fungus and bacteria. Targeting sulfide metabolism may enable us to develop anti-microorganismal agents, which are based on novel mechanisms. Furthermore, because abundance of sulfide-producing bacteria is known to correlate with a number of bowel diseases including inflammatory bowel disease, manipulating sulfide metabolism may also prove to be therapeutic against diseases of host.

The role of NO/cGMP-dependent mechanisms in blood-related disorders

We are examining the role of NO/cGMP-dependent mechanisms in blood-related disorders including hypercoaguability after cardiac arrest and storage lesion of blood. In particular, we are studying the effects of NO/sGC-dependent signaling in a newly developed murine model of hemorrhagic shock-induced cardiac arrest resuscitated with stored blood. Insight gained from these studies may lay foundations to develop novel therapeutic approach to transfusion-related critical illness.

Post-cardiac arrest sedation on brain injury and neurological recovery

Although post cardiac arrest patients are routinely sedated with anesthetics (e.g., propofol), effects of post-arrest sedation on post-arrest outcomes are unknown. We are investigating the role of post-cardiac arrest sedation on brain injury and neurological recovery using a mouse model of cardiac arrest and CPR. Effects of post-arrest sedation with propofol and dexmedetomidine on neurological outcomes are examined using telemetric EEG, cerebral blood flow measurements with laser Doppler flowprobe, histological analysis and neurological functional analysis using a well-established mouse model of cardiac arrest and CPR.