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At the University of South Florida’s Hyperbaric Biomedical Research Laboratory, ongoing work to combat oxygen toxicity seizures in Navy divers has expanded to include research that may lead to non-toxic cancer therapies combining dietary supplements and hyperbaric oxygen.

Jay Dean, PhD, professor in the Department of Molecular Pharmacology and Physiology, USF Health Morsani College of Medicine, created and has directed the collaborative research facility since it opened in 2006.  The laboratory houses chambers that can mimic the adverse environments of high atmospheric pressure (hyperbaric) experienced by deep-sea divers. With instrumentation specially designed to operate under extreme pressures, Dr. Dean and his colleagues can analyze the molecular responses of cells as well as the physiological changes in animal models exposed to changing concentrations of oxygen, nitrogen and other gases.

Jay Dean, PhD, professor of molecular pharmacology and physiology, established and directs the USF Hyperbaric Biomedical Research Laboratory.

To date, Dr. Dean and his USF colleague, Dominic D’Agostino, PhD, have adapted electrophysiology, radio-telemetry and various types of microscopy techniques for use under hyperbaric pressures, including fluorescence, confocal and atomic force microscopy.

“Atomic force microscopes are common, but not atomic force microscopes placed under hyperbaric pressure,” said Dr. Dean, one of the world’s leading experts in hyperbaric neurophysiology. “We’ve been able to successfully apply very powerful research tools to these unique conditions.” 

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Probing oxygen toxicity’s role in seizures

In the last decade Dr. Dean’s laboratory, sponsored by the Office of Naval Research Undersea Medicine Program, has helped shed light on the role of hyperbaric oxygen toxicity in triggering seizures. The condition can be a life-threatening by-product of breathing too much oxygen at high ambient pressures that impacts deep-sea divers as they swim deeper and longer.

Navy SEALs are especially at risk because they wear a closed circuit rebreather, to mitigate the narcotic and other debilitating effects of nitrogen and carbon dioxide breathed under increasing ocean pressure. The special device filters out these gases in such a way that bubbles do not appear on the water’s surface – useful in helping avoid enemy detection. However, the additional stealth comes at a cost. The ratio of oxygen the divers breathe greatly increases the deeper they plunge (essentially becoming pure oxygen) and, when combined with physical exertion and mission stress, can lead to nausea, dizziness, seizures, and even coma or death – all symptoms of oxygen toxicity.

Deep-sea divers can be at risk for oxygen toxicity seizures, a life-threatening condition caused by breathing too much oxygen at high ambient pressures. – U.S. Department of Defense photo

A possible countermeasure, anti-seizure sedatives, requires high doses that could impair warfighters’ mental and physical performance.

Without a reliable way to treat oxygen toxicity or predict which divers are more prone to seizures than others, the Navy takes rigorous precautions to restrict all divers to no more than 10 minutes in 50 feet of seawater.

“This risk of central nervous system oxygen toxicity limits oxygen’s use — not only in diving operations, but also its clinical applications in hyperbaric oxygen therapy,” Dr. Dean said.

Hyperbaric oxygen therapy, which increases blood oxygen to temporarily restore blood gases and tissue function, can help treat unhealed wounds, burns, crushing injuries, decompression sickness, carbon monoxide poisoning, and other medical conditions. The therapeutic benefit might be maximized if the doses of hyperbaric oxygen administered could be boosted without the risk of central nervous system oxygen toxicity.

In their search to find solutions, Dr. Dean and colleagues analyze the response of individual brain cells to the powerful effects of oxygen and other gases under altered pressure. In the laboratory’s hyperbaric chambers, they measure changes in brain cell membranes and electrical activity, and the damage of oxygen-induced free radicals.

An intracellular recording of the electrical signaling by a brain cell (middle trace) in a rodent brain slice that is stimulated by hyperbaric oxygen (top trace).

The researchers also monitor physiological changes in the breathing and heart rate of normal rats moving about in a chamber mimicking the environment of an increasingly deep dive. An electroencephalogram (EEG) shows electrical signals in the brain in real time, indicating the hyperexcitability that precedes and peaks with oxygen toxicity seizures.

Promising discoveries to predict, delay seizures

The USF group has made what could be a key discovery – the breathing rate of the rats exposed to pure oxygen increases several minutes before a seizure starts. “This may be a biomarker – a physiological signal that predicts the impending seizure,” Dr. Dean said.

If this early-predictor hypothesis bears out in larger animal models, Dr. Dean said, the next step would be to work with the Navy to devise and test a mask-fitted with a device designed to monitor divers’ breathing underwater. The ultimate aim: preventing oxygen-induced seizures to safely allow Navy SEALs to dive deeper and longer.

Another of the laboratory’s major findings evolved from an idea by Dr. Dean’s former postdoctoral fellow, Dominic D’Agostino, PhD, to harness the power of ketones, natural compounds produced by the body when it burns fat during periods of fasting or calorie restriction.

Dominic D’Agostino, PhD, associate professor of molecular pharmacology and physiology who collaborates with Dr. Dean, has expanded the laboratory’s research to include metabolic therapeutics. His group is investigating the combination of the ketogenic diet and/or ketone supplements with hyperbaric oxygen as a potential non-toxic cancer therapy.

Now an associate professor of molecular pharmacology and physiology, Dr. D’Agostino has focused on better understanding how the ketogenic diet — a special low-carbohydrate, high-fat diet that elevates blood ketones — produces anticonvulsive and neuroprotective effects. And, more recently he has worked with collaborators in academia and industry to develop and test naturally derived and synthetic supplements to boost blood ketones to mimic the ketogenic diet’s therapeutic effects.

Successfully used by physicians to treat drug-resistant epilepsy or other seizure disorders, the ketogenic diet shifts the brain’s energy source from glucose toward using ketones as a super fuel. However, it takes several days, or event weeks, for the body to adapt to this change in brain energy metabolism. That limitation and other problems associated with adhering to such a strict low-carbohydrate diet make nutritional ketosis less than ideal for Navy SEALs on a mission.

“The big advantage of putting the diet in a pill or liquid form is that you can achieve therapeutic ketosis in 30 minutes, instead of a week,” Dr. D’Agostino said.

A microscopic image of neurons hyper-excited by exposure to pure oxygen under high pressure in the hyperbaric chamber.

In a first of its kind study, Dr. D’Agostino tested whether feeding laboratory rats ketone esters and placing them in the hyperbaric chamber simulating underwater conditions could delay oxygen toxicity seizures. It worked.

More research is needed, but the experiments pave the way for a ketone supplement that would allow Navy SEALS to dive longer while protecting them against seizures, Dr. Dean said. “If what we’ve observed in rat model experiments holds true in humans, the Navy diver should be able to increase the amount of time spent at a depth of 50 feet of seawater (10 minutes) by 600 percent… which means that the divers could get more work done with fewer dives.”

“When the brain is running off ketones, it becomes much more resilient in terms of preserving brain energy and preventing a seizure,” Dr. D’Agostino said.

Based on research led by Dr. D’Agostino, USF has several patents pending for producing brain metabolism-enhancing ketone supplements, which may have a broad range of applications for neurodegenerative diseases like Alzheimer’s and ALS, diabetes and certain cancers as well as seizure disorders – all associated with impairments in metabolic regulation.

Earlier this year USF hosted the first international conference drawing doctors and researchers to discuss the effects of nutritional ketosis and metabolic therapeutics on the treatment of various diseases.

Stephanie Ciarlone, MS, a doctoral student in the USF Health Byrd Alzheimer’s Institute Laboratory of Edwin Weeber, PhD, (seated) professor of molecular pharmacology and physiology. Ciarlone’s preclinical studies of ketone esters in an Angelman syndrome mouse model are helping lay the foundation for what may be the first clinical trial of a USF-developed ketone ester in children with the rare neurogenetic disorder. — Photo by Sandra C. Roa, USF Health Communications

Among the presenters was Stephanie Ciarlone, MS, a doctoral student in the USF Health Byrd Alzheimer’s Institute laboratory of Edwin Weeber, PhD, where her research focuses on treatment options for Angelman syndrome, including ketone esters. This rare neuro-genetic disorder affects young children who commonly suffer debilitating drug-resistant seizures as the condition worsens.

With Dr. D’Agostino as a collaborator, a recent study by Ciarlone found that ketone supplements, without dietary restriction, delayed the onset of seizures and reduced the their number by 50 percent in a mouse model of Angelman syndrome. The ketone esters also improved learning and memory and motor coordination in the mice.

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Dr. Weeber, professor of molecular pharmacology and physiology, is working with Dr. D’Agostino to move their preclinical studies to the first clinical trial of a USF-developed ketone ester in children with Angelman syndrome. The study is expected to begin within a year.

From neuroprotection to exploring non-toxic cancer therapy

A serendipitous thing happened while Dr. D’Agostino and Angela Poff, PhD, research associate, were studying the neuroprotective effects of ketone supplements in different cell models. While examining cancer cells under a microsope specially designed to withstand the barometric pressure in the hyperbaric chamber, they observed that these cells were selectively vulnerable to high pressure oxygen at levels not harmful to healthy cells. They also noticed that the cancer cells did not proliferate when put in a petri dish with ketone supplements as a fuel source.

Cancer cells exhibit altered metabolic processes that could potentially be exploited to shut down their proliferation and survival. Solid tumors have areas of low oxygen, or hypoxia, that actually help promote a cancer’s aggressive growth. “So, the idea was that if we put more oxygen into the blood, which is what the hyperbaric oxygen chamber does, it will diffuse further into the tissue and help shut down areas promoting the tumor growth,” Dr. Poff said.

Angela Poff, PhD, research associate, led a study targeting cancer metabolism with hyperbaric oxygen and ketosis.

In addition, cancer cells use carbohydrate-derived glucose to generate most of their energy, so some research suggests a ketogenic diet that rigorously limits carbohydrates may help slow cancer’s growth, Dr. Poff said.

Armed with this two-pronged approach, the researchers embarked on their first cancer experiments in the Hyperbaric Lab. They discovered that combining hyperbaric oxygen and ketosis reduced the proliferation of metastatic cancer cells. Then, moving their research to a mouse model for aggressive metastatic cancer, they showed that combining a ketogenic diet and ketone supplements with hyperbaric oxygen therapy slowed tumor growth and doubled the survival time of the rodents. Their study was published online last year in PLOS ONE and the theory behind this approach was highlighted in an article in Carcinogenesis.

Hyperbaric oxygen by itself only slightly inhibited the spread of cancer in the mice. “But when we combined hyperbaric oxygen with ketosis induced by the ketogenic diet and our ketone ester, the potent synergistic effect was greater than the individual therapies alone,” Dr. Poff said. In particular, adding the ketone ester to the mix of the ketogenic diet and hyperbaric oxygen boosted the anti-cancer effects.

Images of rat brain slices used to study how hyperbaric oxygen disrupts brain cell function to cause seizures.

Next, the USF researchers say they will work on fine-tuning the combination therapy – finding what doses of ketone supplementation and levels of oxygen work to optimize the anti-cancer effects.

While more research is needed, Dr. D’Agostino said, “this combination therapy could represent a non-toxic strategy to help metabolically manage cancer and enhance the effectiveness of standard cancer treatment with chemotherapy and radiation.”

Dr. D’Agostino and Dr. Poff

The USF Hyperbaric Biomedical Research Laboratory houses various pressure chambers, including a 3.2-ton one specially designed for use with an atomic force microscope, which mimic the extreme environmental conditions challenging deep-sea divers.

The USF Hyperbaric Laboratory, including an interview with Dr. Dean, will be included in an upcoming independent documentary on nitrogen narcosis, a major limiting factor in the performance of deep-sea divers. The video will feature Sherri Ferguson of Simon Fraser University in British Columbia, who studies the health effects of narcosis in divers.

Video and photos by Katy Hennig, USF Health Office of Communications 

Some of the same gases in the air we breathe to stay alive can become harmful, even deadly, at increased atmospheric pressure.

“Oxygen becomes toxic and nitrogen starts to act like a narcotic that will anesthetize you in some of these high pressure, or hyperbaric, environments encountered by the military in deep-sea diving or submarine operations,” said Jay Dean, PhD, professor of molecular pharmacology and physiology at the USF Health Morsani College of Medicine.

USF Health’s Jay Dean, PhD, is one of the world’s leading experts in hyperbaric neurophysiology.

  Listen to Dr. Dean talk about the hyperbaric lab.

Dr. Dean, one of the world’s leading experts in hyperbaric neurophysiology, has attracted more than $4 million in external funding from the Office of Naval Research (ONR) Undersea Medicine Program, since joining USF in 2006.

The USF Hyperbaric Biomedical Research Laboratory he established and directs houses various styles of pressure chambers, which mimic the environmental conditions challenging divers who breathe pure oxygen as they swim deeper and longer. The largest, at 3.2 tons, is specially designed for use with an atomic force microscope and patch clamping apparatus to help researchers determine how gases with different solubility affect brain cell function.

To date, Dr. Dean and his USF colleague, Dominic D’Agostino, PhD, have adapted electrophysiology, radiotelemetry and various types of microscopy techniques for use under hyperbaric pressures, including fluorescence, confocal and atomic force microscopy.

“Atomic force microscopes are common, but not atomic force microscopes placed under hyperbaric pressure,” Dr. Dean said. “In our lab, we’ve been able to apply very powerful research tools to unique conditions.”

Dr. Dean’s lab will soon send its second graduate student to work as a physiologist at the Navy’s medical research center. “At USF, we are helping train the next generation of undersea medicine experts in the novel techniques needed to study human performance under extreme conditions.”

The USF Hyperbaric Biomedical Research Laboratory houses various pressure chambers, including a 3.2-ton one specially designed for use with an atomic force microscope, which mimic the extreme environmental conditions challenging deep-sea divers.

Shedding light on role of oxygen toxicity in seizures

Dr. Dean started his career studying the effects of carbon dioxide on the neural control of breathing and cardiovascular function. His collaborations with the Department of Defense and Undersea Medicine program shifted his primary focus to the role of oxygen toxicity in seizures as well as the toxic effects of carbon dioxide retention.

Recently, Dr. Dean’s team expanded the scope of their hyperbaric neurosciences research by probing the cellular mechanisms of nitrogen narcosis, a major factor limiting divers’ safety and performance. This new research direction was supported by a transfer of $700,000 of equipment to USF from the Navy’s Experimental Diving Unit in Panama City, FL. In addition, Dr. D’Agostino’s team, housed with Dr. Dean in the Hyperbaric Biomedical Research Lab, has broadened the work on hyperoxia to include studies that may lead to non-toxic cancer therapies combining dietary supplements and hyperbaric oxygen.

Over the last decade Dr. Dean’s research has helped shed light on the role of hyperbaric oxygen toxicity in triggering seizures. The condition can be a life-threatening by-product of breathing too much oxygen at high ambient pressures that impacts deep-sea divers as they swim deeper and longer.

Deep-sea divers can be at risk for oxygen toxicity seizures, a life-threatening condition caused by breathing too much oxygen at high ambient pressures. – U.S. Dept. of Defense photo

Navy SEALs are especially at risk because they wear a closed circuit rebreather, to mitigate the narcotic and other debilitating effects of nitrogen and carbon dioxide breathed under increasing ocean pressure. The special device filters out these gases in such a way that bubbles do not appear on the water’s surface – useful in helping avoid enemy detection. However, the additional stealth comes at a cost. The ratio of oxygen the divers breathe greatly increases the deeper they plunge (essentially becoming pure oxygen) and, when combined with physical exertion and mission stress, can lead to nausea, dizziness, seizures, and even coma or death – all symptoms of oxygen toxicity.

A possible countermeasure, anti-seizure sedatives, requires high doses that could impair warfighters’ mental and physical performance.

Without a reliable way to treat oxygen toxicity or predict which divers are more prone to seizures than others, the Navy takes rigorous precautions to restrict all divers to no more than 10 minutes in 50 feet of seawater.

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Applications extend beyond undersea medicine

“This risk of central nervous system oxygen toxicity limits oxygen’s use — not only in diving operations, but also its clinical applications in hyperbaric oxygen therapy,” Dr. Dean said.

Hyperbaric oxygen therapy, which increases blood oxygen to temporarily restore blood gases and tissue function, can help treat unhealed wounds, burns, crushing injuries, decompression sickness, carbon monoxide poisoning, and other medical conditions. The therapeutic benefit might be maximized if the doses of hyperbaric oxygen administered could be boosted without the risk of CNS oxygen toxicity.

In their search to find solutions, Dr. Dean and colleagues analyze the response of individual brain cells to the powerful effects of oxygen and other gases under altered pressure. In the laboratory’s hyperbaric chambers, they measure changes in brain cell membranes and electrical activity, and the damage of oxygen-induced free radicals.

The researchers also monitor physiological changes in the breathing and heart rate of normal rats moving about in a chamber mimicking the environment of an increasingly deep dive. An electroencephalogram (EEG) shows electrical signals in the brain in real time, indicating the hyperexcitability that precedes and peaks with oxygen toxicity seizures.

An intracellular recording of the electrical signaling by a brain cell (middle trace) in a rodent brain slice that is stimulated by hyperbaric oxygen (top trace).

Promising discoveries to predict, delay seizures

The USF group made what could be a key discovery – the breathing rate of the rats exposed to pure oxygen increases several minutes before a seizure starts. “This may be a biomarker – an early physiological signal that predicts the impending seizure,” said Dr. Dean, who was principal investigator for the study published in the Journal of Applied Physiology.

If this early-predictor hypothesis bears out in larger animal models, he said, the next step would be to work with the Navy to devise and test a mask-fitted with a device designed to monitor divers’ breathing underwater. The ultimate aim: preventing oxygen-induced seizures to safely allow Navy SEALs to dive deeper and longer.

Another of the laboratory’s major findings evolved from an idea by Dr. D’Agostino, Dr. Dean’s former postdoctoral fellow who is now an associate professor, to harness the power of ketones, natural compounds produced by the body when it burns fat during periods of fasting or calorie restriction.

They’ve focused on better understanding how the ketogenic diet — a special low-carbohydrate, high-fat diet that elevates blood ketones and alters brain metabolism — produces anticonvulsive and neuroprotective effects. The diet has been successfully used to treat drug-resistant epilepsy or other seizure disorders.

Dr. Dean with laboratory colleagues Angela Poff, PhD, research associate, and Dominic D’Agostino, PhD, associate professor, all members of the Department of Molecular Pharmacology and Physiology.

  Dr. Dean comments on the team’s two approaches to studying oxygen toxicity seizures.

Working with collaborators in academia and industry, USF continues to develop and test naturally derived and synthetic supplements that will more rapidly mimic the therapeutic effects of ketosis without the problems associated with adhering to the ketogenic diet.

In a first of its kind study, Dr. D’Agostino and Dr. Dean tested whether feeding laboratory rats a ketone ester and placing them in the hyperbaric chamber simulating underwater conditions could delay oxygen toxicity seizures. It worked. Their study was published in the American Journal of Physiology: Regulatory, Integrative and Comparative Physiology. They also hold a patent on the use of the USF-developed ketone ester, a highly efficient fuel for the brain, to prevent CNS oxygen toxicity.

More research is needed, but the experiments pave the way for a ketone supplement that would allow Navy SEALs to dive longer while protecting them against seizures, Dr. Dean said. “If what we’ve observed in rat model experiments holds true in humans, the Navy diver should be able to increase the amount of time spent at a depth of 50 feet of seawater (10 minutes) by 600 percent… which means that the divers could get more work done with fewer dives.”

The USF Hyperbaric Laboratory will be included in an upcoming independent documentary on nitrogen narcosis, which features Sherri Ferguson, a colleague of Dr. Dean’s from Simon Fraser University in British Columbia, who studies the health effects of narcosis in deep-sea divers.

Unmatched expertise in hyperbaric cellular electrophysiology

Earlier this year, Sherri Ferguson, director of the Environmental Medicine and Physiology Unit at Simon Fraser University in British Columbia, visited Dr. Dean’s lab to observe and collaborate on some experiments investigating brain cell response to nitrogen under pressure. Ferguson, helping to make a documentary on nitrogen narcosis and its health effects in deep-sea divers, brought along the independent filmmaker who included an interview with Dr. Dean in the piece.

When breathed beneath the ocean’s depths, nitrogen can create state of mental impairment similar to the intoxicating effect of alcohol.

Ferguson recently visited Dr. Dean’s lab to collaborate on some experiments investigating brain cell response to nitrogen under pressure. “Dr. Dean has the only cellular hyperbaric electrophysiology lab of its kind in North America,” she said.

Ferguson says she was attracted to the USF Hyperbaric Biomedical Research Laboratory by Dr. Dean’s development of continuous intracellular recordings measuring how mammalian neurons behave under varying gas and pressure conditions.

“Dr. Dean has the only cellular hyperbaric electrophysiology lab of its kind in North America. His expertise in this field is unmatched, so I was excited to learn from him,” she said. “To leave him out of a documentary on cellular mechanisms of narcosis would not accurately reflect where the research is today and where it is going in the future.”

A microscopic image of neurons hyper-excited by exposure to pure oxygen under high pressure in the hyperbaric chamber.

Something you might not know about Dr. Dean:

He has spent 33 years researching the physiological problems of flight encountered by World War II pilots and their crews, who flew at high altitudes in unpressurized aircraft and suffered hypoxia from lack of oxygen and decompression sickness from low pressure.

Dr. Dean is writing a book on advances by the Allies in aviation physiology research during the war and has presented on this topic across the United States. His impressive collection of historical documents, manuscripts, films and other artifacts from Wright Field Aeromedical Laboratory (Dayton, Ohio) and several universities and medical centers documents the pioneering work on oxygen equipment, G-suits, high-altitude parachute escape, explosive decompression and development of the first pressurized airplanes.

This photo from the Mayo Historical Unit Archives shows the team of researchers from the Wright Field Aero Med Lab and Mayo Aero Med Unit before the aircraft Nemisis, a B-17E testing platform used during World War II, takes off for a study of the opening shock of a parachute at high altitude. Physiologists trained a 145-pound St. Bernard dog, Major, (lower right) to parachute — simulating the jump of a man. Major wore protective clothing and an oxygen mask during his descent.

Listen to Dr. Dean’s recent presentation on WWII aeromedical research at the Institute of Human and Machine Cognition lecture series.

Photos by Katy Hennig, USF Health Communications

The Office of Naval Research recently released a video it produced highlighting the undersea medicine research projects taking place around the country, including the work by a team at the USF Hyperbaric Biomedical Research Laboratory (HBRL).

Videographer David Taylor and his team met last fall with USF Health’s Jay B. Dean, PhD, who created the HBRL and has directed it since it opened in 2000. The crew spent the better part of the day interviewing Dr. Dean and other lab members, hearing about the current projects of the lab.

Dr. Jay Dean

While the video looks at several facilities conducting studies related to different aspects of undersea medicine, Dr. Dean’s section of the video focuses on brain cell response to hyperbaric conditions.

“Oxygen is a drug,” Dr. Dean explained on camera last fall. “When the percentage of oxygen increases, it starts to have a powerful effect. Too much, you can have a grand mal seizure. It’s hard to predict. Cells involved with breathing are sensitive to oxygen, so we measure those levels to help predict when it’s too much. We look at cell membrane, its stickiness and fluidity.”

In addition, the USF team is looking at preventing oxygen toxicity using ketone esters, a highly efficient fuel for the brain that seems to delay seizures better than current medicine used to prevent seizures or ketogenic diets, a high-fat, adequate-protein, low-carbohydrate diet.

USF Hyperbaric Lab team

The USF Hyperbaric Biomedical Research Laboratory is a collaborative research facility housed in the Department of Molecular Pharmacology and Physiology. The HBRL maintains several hyperbaric/hypobaric pressure chambers containing equipment used to measure cellular function in real time via electrophysiology, polarography, fluorescence microscopy and atomic force microscopy during experimental perturbations of barometric pressure and gas partial pressures. 

The mission of the USF-HBRL is to identify the molecular and cellular mechanisms involved in the body’s response to artificial atmospheres and altered pressure environments, including low barometric pressures (hypobaria), normal sea level pressure (normobaria) and high barometric pressures (hyperbaria).  Altered pressure environments perturb various cellular processes at the molecular level due to the effects of pressure per se, gas partial pressure alone, and/or the production of secondary reaction productions such as O2-induced free radicals or CO2-induced protons.  Altered pressure environments are routinely encountered in hyperbaric medicine (hyperbaric oxygen therapy), underwater diving (hyperbaric gases) and space exploration (hypobaric gases). 

To study cellular processes under these conditions, Dr. Dean and his colleagues at USF, Dr. Dominic D’Agostino (Molecular Pharmacology and Physiology), has assembled six hyperbaric/hypobaric pressure chambers for in vitro and in vivo biomedical research.  The design, development and implementation of these novel research tools have been funded primarily through equipment grants from the Department of Defense and Office of Naval Research (ONR), Undersea Medicine Program.  Ongoing basic research by the USF-HBRL team is currently supported by the ONR, NIH and USF College of Medicine.