Four teams of University of Alabama at Birmingham researchers have been awarded National Science Foundation grants totaling $5.4 million meant to stimulate competitive research in regions of the country that are less able to compete for these research funds.

One research team supported by an NSF grant is in the College of Arts and Sciences’ Department of Chemistry, led by a polymer chemist who applies nanotechnology to biological and biomedical challenges. The three other grants will support basic neuroscience studies, one of UAB’s hallmark research strengths.

Lori McMahon, Ph.D., the Jarman F. Lowder Professor of Neuroscience, dean of the UAB Graduate School and director of the UAB Comprehensive Neuroscience Center, highlighted the three neuroscience EPSCoR grants at this fall’s Comprehensive Neuroscience Center retreat, calling them prestigious and competitive.

“UAB neuroscience has never had one NSF grant, and now we have three,” she said. “With the results of these grants, we can increase our funding beyond the National Institutes of Health.”

These four UAB grants, and one additional Alabama-related EPSCoR that supports research teams at the University of Alabama, Tuscaloosa, and the University of Mississippi, set a record, says Christopher Lawson, Ph.D., executive director of the Alabama EPSCoR program and a professor in the UAB Department of Physics.

“The state of Alabama now has more of the EPSCoR Track II grants than any other state; no state has ever had five.” 

Only 25 states, two territories and one commonwealth — areas that receive much less NSF funding than the major research universities in the other 25 states — qualify to compete for the Experimental Program to Stimulate Competitive Research grants, known as EPSCoR. The EPSCoR Track II grants are meant to level the playing fields among have and have-not research states, and applicants must form collaborations with researchers from other EPSCoR states. This means the UAB teams have formed synergistic partnerships and collaborations across the Birmingham campus and with scientists in other states to foster regional research strength. escor graphic

UAB neuroscience teams and their goals

The three neuroscience EPSCoR grants support a study to understand the initiation of epileptic brain seizures; a project to develop a new tool for optogenetics, which is the control of neural cells using light; and an effort to discover a universal rule for the relation between neural activity and increased blood flow in areas of the brain. In all three EPSCoR grants, UAB is a partner institution, and the lead institution is in another EPSCoR state.

“Several institutions reached out to UAB because we are so strong in neuroscience,” McMahon said. “There is a lot of UAB synergy around the three neuroscience EPSCoRs.”

McMahon says all three UAB neuroscience teams will meet regularly to share results and ideas.

Epileptic brain seizures

nsf grants martinFrom left: Roy Martin, Jerzy P. Szaflarski and Timothy Gawne.The current approach for epilepsy surgery at UAB involves two surgeries. The first implants electrodes into a patient’s brain for a two-week period to map the location of the seizure onset zone in the brain. The second operation cuts out the onset zone.

“Our goal is to one day not need invasive monitoring,” said Sandipan Pati, M.D., assistant professor of neurology. “That would mean one surgery instead of two, and the patient would not have to stay in the hospital for two weeks.”

The UAB team in the epileptic brain seizure study — headed by Jerzy P. Szaflarski, M.D., Ph.D., professor of neurology — is developing and validating software for noninvasive brain mapping that will allow caregivers to locate that part of the brain that initiates seizures and locate those parts that function in memory.

“We will provide a road map for the surgeons — where to operate to remove the thumb-sized part of the brain that kicks off seizures, and what parts of the brain to avoid,” Pati said, “so that patients will have no added memory deficits after the operation.”

The investigators will use magnetoencephalography, or MEG, to map electrical activity using the magnetic fields produced by natural electrical currents produced by the brain. The magnetic forces are measured from the outside of the brain as the top of a patient’s head fits into the MEG device, which looks something like a beauty-shop hair drier on steroids. Pati says the UAB team has preliminary data about using the MEG to identify the onset zone by its hyper-excitation, without the need to wait for seizures.

Other UAB investigators in the study are Roy Martin, Ph.D., associate professor of neurology, and Timothy Gawne, Ph.D., associate professor of vision sciences. The lead institution for the study is Louisiana Tech University, and the University of Arkansas is also a partner in the study.

New tool for optogenetics

nsf grants mcmahonFrom left: Mark Bolding, Lynn Dobrunz, Lori McMahon and Gary Gray.Optogenetics uses light to control cells in living tissue, after light-sensitive ion channels are introduced into the cells by gene manipulation. Then light is sent into the brain on a fiber-optic cable inserted into the brain, to make neurons fire or to stop neurons from firing. This control helps researchers learn how the brain is wired and how it works.

The optogenetics project will create technology to control the light-sensitive ion channels using low-power X-rays, thus allowing control of neurons from outside the body.

McMahon is the UAB co-principal investigator in this project, which is led by Clemson University. Other partner institutions are the University of New Mexico and the University of South Carolina. The Clemson researchers will develop special nanoparticles that emit light in response to X-rays, the New Mexico researchers will genetically modify the light-sensitive ion channels so that they can bind the nanoparticles, and the UAB researchers will test how those nanoparticles disperse in the brain and how these particles, when activated by X-rays, can turn on and off brain circuits.

“We are about to do the first validation,” McMahon said. “The entire four years of the grant is developing the tool. Then we can use it in animal disease models for Alzheimer’s disease, Parkinson’s disease and anxiety. The goal is to understand brain circuitry using preclinical models of neurologic disease and models of neuropsychiatric illness.”

Other UAB investigators are Lynn Dobrunz, Ph.D., associate professor of neurobiology; Mark Bolding, Ph.D., assistant professor in the Division of Advanced Medical Imaging Research, Department of Radiology, and director of the Civitan International Neuroimaging Facility; Kazutoshi Nakazawa, M.D., Ph.D., associate professor of psychiatry and behavioral neurobiology; and Gary Gray, Ph.D., professor of chemistry.

Neural activity and blood flow

nsf grants lubinJacques Wadiche, Farah Lubin and Paul Gamlin.It has long been known that neural activity is associated with increased blood flow, as the neurons need more oxygen and nutrients. In imaging with functional magnetic resonance, or fMRI, increased blood flow can be seen in parts of the brain as the subjects perform a task. But the resolution — both spatially and in time — is not sharp, and fMRI remains an indirect measure of neural activity.

The UAB team will use a very expensive infrared laser and microscope to peer beneath the surface of living brains to look at individual neurons and capillary beds.

“We will image cells in the brain using two-photon imaging,” said Paul Gamlin, Ph.D., professor of ophthalmology and UAB’s co-principal investigator in the neural activity and blood flow effort. “While monitoring neural activity, we will also monitor what the capillary bed is doing.”

“The question is, if we stimulate the cells, how precise is the blood flow change?”

Capillaries are the smallest blood vessels, bringing oxygen and nutrients to cells and taking away carbon dioxide and waste products. Networks of capillaries form tiny beds of vessels, and each capillary has a precapillary sphincter, a ring of muscle that can control blood flow, akin to crimping a garden hose to lessen water flow. It has been estimated that the human brain has 400 miles of capillaries, and that nearly every neuron in the brain has its own capillary.

Gamlin and others on the UAB team — Lawrence Sincich, Ph.D., assistant professor of vision sciences; Farah Lubin, Ph.D., associate professor of neurobiology; Jacques Wadiche, Ph.D., associate professor of neurobiology; and Yuhua Zhang, Ph.D., assistant professor of ophthalmology — can stimulate neurons nonphysiologically and see how the capillaries change. They will also look at physiological stimulation by shining light on one, two or three retinal cells in the eye and watching how neurons and capillaries in the visual cortex of the brain respond.

The lead institution in this project is the Medical University of South Carolina, and Furman University and the University of South Carolina, Beaufort, are partners in the study.

Detecting pollutants in Gulf Coast marine ecosystems

eugenia kharlampieva 2016Eugenia KharlampievaThe Gulf Coast aquatic ecosystem hosts important fishing grounds and aquaculture, which co-exist with trading ports, off-shore oil wells and production industries. The fourth UAB EPSCoR is aimed at monitoring the water quality of this ecosystem, under the lead of the University of Southern Mississippi.

Ten researchers at six institutions in Alabama and Mississippi will develop advanced polymer-based, selective sensing technologies to detect and analyze pollutants.

The UAB investigator is Eugenia Kharlampieva, Ph.D., associate professor of polymer chemistry. She will design and synthesize three-dimensional porous hydrogel microparticles. These particles will be filled with sensing molecules created by Marco Bonizzoni, assistant professor of chemistry at the University of Alabama, Tuscaloosa. These hydrogels will eventually become devices that can sense polycyclic aromatic hydrocarbons in sea water.

“Sea water is a challenge because it is very rich in ions from all that salt,” Kharlampieva said. “It is hard to find the right technology that will work in that environment.”

Other researchers in the grant are developing sensitive and selective sensors to measure levels of carbon dioxide, nitrates and phosphates. The goal is new classes of seawater quality sensors that are faster, simpler and less costly. Other partner institutions in the grant are the University of Mississippi, Mississippi State University and Jackson State University.





By Jeff Jeff Hansen
UAB Media Relations

 

jerzy szaflarskiJerzy Szaflarski, M.D., Ph.D., professor of neurology Jerzy Szaflarski, M.D., Ph.D., director of the University of Alabama at Birmingham Epilepsy Center, has been named a fellow of the American Epilepsy Society.

Szaflarski joined the UAB Department of Neurology in fall of 2013 as a professor and the director of the Division of Epilepsy.

The American Epilepsy started the fellows program to encourage epilepsy professionals by supporting their research and career development. Fellows are invited to attend the AES Annual Meeting to learn about the latest findings in research and meet with mentors about career planning.

Fellows are awarded a monetary grant of $750 and a one-year AES membership. While attending the annual AES meeting, Szaflarski will be giving a presidential lecture

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   UAB researchers release new research findings on effect of CBD oil at national Epilepsy Society Meetings

 jerzy groupLeslie Perry, M.D., Jerzy Szaflarski, M.D., Ph.D., and Tyler Gaston, M.D., are among the UAB researchers presenting findings of the CBD oil studies.

BIRMINGHAM, Ala. – Cannabidiol oil, also known as CBD oil, reduces the frequency and severity of seizures in children and adults with severe, intractable epilepsy, according to findings presented by researchers from the University of Alabama at Birmingham at the American Epilepsy Society 70th Annual Meeting.

UAB researchers presented eleven abstracts, or research findings, at the meeting. A key finding was that CBD provided a significant reduction in frequency of seizures for a majority of the patients in the study, and that approximately two-thirds of patients saw a greater than 50 percent reduction in severity.

“It is encouraging that both frequency and severity of seizures appear to improve in the majority of patients in our study, patients who have limited treatment options,” said Jerzy P. Szaflarski, M.D., Ph.D., professor in the Department of Neurology and director of the UAB Epilepsy Center. “Our research adds to the evidence that CBD may reduce frequency of seizures, but we also found that it appears to decrease the severity of seizures, which is a new finding.”

The results were based on an open-label study of 81 patients — 42 children and 39 adults — who experienced four or more seizures per month. UAB launched the studies of CBD oil as a treatment for severe, intractable seizures in April 2015. The studies, an adult study at UAB and a pediatric study at Children’s of Alabama, were authorized by the Alabama Legislature in 2014 by legislation known as Carly’s Law.

After one month of beginning CBD therapy, 68 percent of the patients had experienced a greater than 25 percent reduction in seizure frequency; 58 percent had a greater than 50 percent reduction; 36 percent had a greater than 75 percent reduction and 9 percent were seizure-free. Those results were maintained at three and six months.

To assess seizure severity, researchers led by Jenifer DeWolfe, M.D., associate professor of neurology, used the Chalfont Seizure Severity Scale, a questionnaire given prior to therapy and re-administered at intervals throughout treatment. Fifty-seven patients were followed for three months: 67 percent experienced a more than 50 percent decrease in seizure severity, while 33 percent did not. Of 47 patients followed for six months, 64 percent had a greater than 50 percent decrease in seizure severity and 36 percent did not.

 “These are encouraging results, but it is important to note that each patient may respond differently to CBD, and the dose for optimal seizures control varies,” said Martina Bebin, M.D., professor of neurology and co-primary investigator of the CBD studies. “There appears to be an optimal CBD dose range where the patient achieves maximum benefit. If outside this CBD dosing range, the seizure frequency may not improve and may even increase. More research is needed, including determining why and how CBD helps some people with epilepsy but not others.”

Among the other UAB abstracts presented at the AES meetings:

·         CBD oil was associated with an improvement in mood, an effect independent of the extent of seizure reduction. Lead author Pongkiat Kankirawatana, M.D., professor of pediatrics, says CBD oil may have overall positive effects on mood, which should be further investigated in patients with epilepsy and other chronic conditions in controlled studies.

·         A study led by Szaflarski and Bebin found that the optimum dose in both children and adults was between 20 and 25 mg/kg/day.

·         Jane Allendorfer, M.D., assistant professor of neurology, found that CBD, in a selected group of patients with epilepsy who experienced overall improved seizure control, has the potential for positive cognitive effects that are associated with corresponding fMRI signal changes.

·         One abstract reports on an interaction between warfarin, a drug used as an anticoagulant, and CBD. This underscores the importance of monitoring appropriate laboratory work in patients receiving CBD oil along with other medications, according to study lead Brannon Vines, M.D., a clinical neurophysiology fellow.

·         Significant drug interactions were identified between CBD and commonly-used medications for epilepsy, including clobazam, rufinamide, topiramiate, zonisamide and eslicarbazepine. This study, led by neurology fellow Tyler Gaston, M.D., emphasizes the importance of monitoring anti-epilepsy drug levels during treatment with CBD. 

·         Electrical discharges measured by EEG decreased significantly after initiation and maintenance of CBD, particularly in pediatric patients, according to a study led by Leslie Grayson, M.D., a neurology fellow.

·         Using fMRI imaging, Amber Gregory, a graduate student in psychology, showed that persons with epilepsy showed gains in working memory that were associated with a shift in neural recruitment as examined with functional MRI.

·         An abstract aimed at examining associations between social determinants of health, such as age, gender and socioeconomic factors against health status, quality of life and mood states showed that higher age and low income were associated with lower health ratings among epilepsy patients, according to study led Magdalena Szaflarski, Ph.D., assistant professor of sociology.

The studies are designed to test the safety and tolerability of CBD oil in patients with intractable seizures. CBD oil, a derivative of the cannabis plant, is delivered orally as an oily liquid.

The oil used in the studies is produced under stringent requirements of the United States Food and Drug Administration by a licensed pharmaceutical company. It contains only traces of THC, the psychoactive component of marijuana. The process developed by GW Pharmaceuticals guarantees the consistency of the product that is provided to study participants.


By Bob Shepherd
UAB Media Relations

energy drinksVenkatraman says the drink contains a high level of caffeine, along with a variety of other ingredients, many of which are associated with increases in blood pressure.Investigators at the University of Alabama at Birmingham have presented the first case study of a patient experiencing a hemorrhagic stroke — a brain bleed — following consumption of an energy drink.

In an article in press in the American Journal of Emergency Medicine, the UAB physicians detail the case of a 57-year-old man who developed an intracranial hemorrhage within 15 minutes of drinking a popular energy drink.

The patient presented at a local emergency department and was transferred to the stroke unit at UAB with symptoms of sensory changes (tingling and numbness) in the right arm and leg, along with ataxia (shaky gait and movement). A CT scan revealed a small hemorrhage near the left thalamus.

“The man reported that his symptoms began about 15 minutes after drinking an energy drink, the first time he had consumed this particular product, as he was about to do yardwork,” said Anand Venkatraman, M.D., a fourth-year resident in the Department of Neurology at UAB and the lead author of the study.

Venkatraman says the drink contains a high level of caffeine, along with a variety of other ingredients, many of which are associated with increases in blood pressure.

“This particular drink contains several supplements for which we have little understanding of their potential interactions with each other or with caffeine,” Venkatraman said. “One is structurally similar to amphetamines, and several are known to stimulate the sympathetic nervous system.”

The sympathetic nervous system regulates what is known as the “flight or fight” response. When faced with an urgent, potentially dangerous situation, the body gears up to either take extraordinary action (fight) or run away (flight).

“The body begins to marshal all of its resources to respond to the situation at hand — boosting strength and alertness, for example — in part by raising blood pressure to increase blood flow,” Venkatraman said. “For a patient who may be at risk for vascular disease, this increase in blood pressure could be potentially dangerous, as a rise in blood pressure can affect an already weakened blood vessel to the point that it ruptures.”

Ingredients in the drinks that are suspected to influence the sympathetic nervous system include β-phenylethylamine hydrochloride, yohimbine and green tea extract. 

“These ingredients are supplements and, as such, are not regulated by the government to the same degree that medications are,” Venkatraman said. “We don’t have good information on dosing for some of these supplements. We don’t know how much is too much, for example, especially in populations with varying degrees of risk.”

Another issue is serving size. The manufacturer’s label says the bottle contains two servings, but the patient reported that he drank the full 8 oz. bottle at one time, a behavior that Venkatraman believes is common.

“The warning here is that we do not fully understand how some of these ingredients interact with other compounds,” Venkatraman said. “Nor do we have enough information on maximum dosages, especially for individuals with underlying health issues. Consumers need to be aware of the ingredients in the drinks if they choose to use them, and check with their physician if they have questions. They should also follow the manufacturer’s recommendations.”

 In this case, the patient had a history of elevated blood pressure and was at increased risk for vascular disease. Several months after the incident, the patient reported that he still had some residual effects from the incident.

“I am not anti-energy drink,” Venkatraman said. “In fact, I use them myself on occasion. But I strongly urge consumers to read the label and be informed. Don’t take unnecessary risks with your health. There is potential for a serious outcome.”

Contributing authors to the study are Angela Shapshak, M.D., associate professor of neurology, and Ayaz Khawaja, M.D., now a fellow in neurology at Harvard Medical School.

By Bob Shepherd
UAB Media Relations