Engineers, physicians, computer scientists and statisticians will collaborate to research and apply big data in the health care, industrial and smart cities fields.

big data hub 2The lab is a joint initiative of the School of Engineering’s Department of Electrical and Computer Engineering, the Department of Neurology in the School of Medicine, and UAB IT Research Computing.The Big Data Research and Analytics Lab in the UAB School of Engineering, along with UAB Information Technology Research Computing and the School of Medicine’s Department of Neurology, will be part of a national effort to develop a Big Data Regional Innovation Hub serving 16 Southern states and the District of Columbia.

The South Big Data Regional Innovation Hub, or South BD Hub — to be managed jointly by Georgia Tech and the University of North Carolina — is part of the National Science Foundation’s four Big Data Regional Innovation Hubs announced today. The new initiative aims to build innovative public-private partnerships that address regional challenges through big data analysis.

“The award of the South Big Data Regional Innovation Hub to Georgia Tech and UNC-Chapel Hill provides the right context for collaboration among 116 stakeholders in academia, industry and the nonprofit sectors, which will enable us to — for the first time — address large-scale challenges facing many Southern states,” said Srinivas Aluru, co-principal investigator and professor in the School of Computational Science and Engineering at Georgia Tech.

Each of the NSF BD Hubs will engage businesses and research organizations in their region to develop common big data goals that would be impossible for individual members to achieve alone. The hubs will develop community-driven governance structures as well as “spoke projects” based on regional priorities and partnerships.

“Big data analysis is changing the way we see the world and is one of the more profound developments in science that we’ve seen in our lifetime,” said Iwan Alexander, Ph.D., dean of the UAB School of Engineering. “At UAB, we are uniquely positioned because of the wide range of expertise here in areas from engineering to medicine to business. Our Big Data Research and Analytics Lab has the potential to touch every part of campus, and as such, it can provide valuable input to this national network.”

In particular, UAB’s contributions to the South BD Hub are expected to be concentrated around the issues of health care, industrial big data and smart cities. UAB’s effort is being led by Thomas Anthony, director of the Big Data Research and Analytics Lab.

The lab is a joint initiative of the School of Engineering’s Department of Electrical and Computer Engineering, the Department of Neurology in the School of Medicine, and UAB IT Research Computing. The lab has been set up to bring together engineers, physicians, computer scientists and statisticians to develop novel ways to manage, analyze and visualize very large data sets.

big data hub 3UAB’s contributions to the South BD hub are expected to be concentrated around the issues of health care, industrial big data and smart cities.In addition to serving as a facility to process data generated at UAB and gathered through research of publicly available datasets, the lab is also working on emerging technologies and approaches to big data analytics that would be applicable to a large number of fields, which demonstrates the potential for big data to make a big impact on 21st century life.

“The important problems of our time — from solving disparities in health care to understanding the risks of coastal storms and floods — involve making sense of massive amounts of data,” said Ashok Krishnamurthy, deputy director at RENCI and co-PI with Aluru on the South BD Hub project. “The chance to lead this project with Georgia Tech means we will be at the forefront of using data for the public good.”

The South BD Hub will serve Alabama, Arkansas, Delaware, the District of Columbia, Florida, Georgia, Kentucky, Louisiana, Maryland, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee, Texas, Virginia and West Virginia. It will be developed in three phases — an initial bootstrap phase that will establish the basic governance structure, a transitional phase that will move toward an operational structure and a final operational phase.

Initial spokes of the South BD Hub will aim to apply big data analysis to scientific and social issues in five areas:

  • Health Care, including disparities in health, access to health care, health outcomes, precision medicine and health analytics.
  • Coastal Hazards, including understanding and mitigating the consequences of natural and manmade disasters.
  • Industrial Big Data, including cyberphysical systems, the Internet of Things, data-driven management of physical infrastructure, and power generation, transmission and distribution from a variety of sources.
  • Materials and Manufacturing, including data-driven contributions to the materials genome initiative and bridging the gap between materials science and manufacturing practice.
  • Habitat Planning, including urban infrastructure, smart cities efforts, transportation, rural-urban infrastructure, and wildlife habitat and conservation.
Initial NSF funding for the South BD Hub will be $1.5 million over three years. In addition to the South BD Hub, the NSF has funded Hubs in the Northeast, Midwest and Western U.S., which are managed by universities in those regions.

A multicenter study led by the University of Alabama at Birmingham
has found a biomarker identified via electroencephalography, or EEG,
that is 100 percent predictive for seizures in infants with tuberous
sclerosis complex. TSC is a genetic disorder that causes nonmalignant
tumors to form in many different organs, primarily in the brain, eyes,
heart, kidney, skin and lungs. The study is published online in Pediatric Neurology.

Approximately 80 percent of TSC patients develop seizures between
birth and age 3. The new EEG biomarker, the first of its kind in TSC
patients, presents as an abnormality in the EEG called an epileptiform
discharge. In the study, all infants with the biomarker developed
seizures within two to three months.

“The earlier seizures are recognized and treated, the better the
developmental outcomes for children with TS,” said E. Martina Bebin,
M.D., professor in the Department of Neurology
at UAB and the study’s senior author. “The development of this
predictive biomarker may provide a critical window of opportunity for
families and medical providers to initiate treatment at seizure onset,
with potentially a positive impact on the infant’s developmental

The study, conducted at five medical centers across the United States, examined 40 children with a diagnosis of TSC.

The presence of the biomarker means families will need to learn the
identifying signs of seizures and begin to involve a neurologist in
their child’s care prior to actual seizure onset. Bebin says the study
reinforces the idea that EEG should be done at time of diagnosis for
TSC, and repeated on a regular basis. The study conducted EEG every six

“The results of this study not only support the importance of that
initial EEG but also the importance of subsequent EEGs in monitoring the
development of seizures and epileptiform discharges,” Bebin said. “Our
study demonstrates the feasibility and importance of close EEG
surveillance in infants with TSC for predicting those who will
subsequently develop epilepsy.”

“The results of this study not only support the importance of that
initial EEG but also the importance of subsequent EEGs in monitoring the
development of seizures and epileptiform discharges. Our study
demonstrates the feasibility and importance of close EEG surveillance in
infants with TSC for predicting those who will subsequently develop

Bebin says further studies are needed to better understand the
relationship between various therapeutic agents and the biomarker, along
with determination of the optimal timeframe in which to begin therapy.

Tuberous sclerosis complex is an autosomal dominant disease that
affects approximately one in 6,000 people and is one of the most common
genetic causes of epilepsy. Almost half of infants with TSC develop
epilepticspasms, which is associated with poor neurological prognosis.

The research team consisted of Bebin, Monisha Goyal, M.D., and Gary
Cutter, Ph.D., with UAB; Joyce Y. Wu, M.D., University of California at
Los Angeles; Jurriaan M. Peters, M.D., Ph.D., and Mustafa Sahin, M.D.,
Ph.D., Boston Children’s Hospital; Darcy Krueger, M.D., Ph.D.,
Cincinnati Children’s Hospital Medical Center; and Hope Northrup, M.D.,
and Kit Sing Au, M.D., University of Texas Medical School at Houston.

The multicenter study was funded by the National Institutes of Health and the Tuberous Sclerosis Alliance.
Pursuing links between inflammation and Parkinson’s, in lab and clinic

Pursuing links between inflammation and Parkinson’s, in lab and clinic

October 13, 2015

By Jeff Hansen

UAB's strengths in clinical care and research are powering an interdisciplinary expedition into largely uncharted territory: neuroinflammatory mechanisms in Parkinson's disease.

A group of UAB researchers have set themselves a two-year target — put an interdisciplinary team in place and have the necessary results in hand that will support the development of a Parkinson’s Disease Research Center of Excellence at UAB. Only nine such NIH-supported centers — also known as Morris K. Udall Centers — exist today, none in the Deep South.

UAB will focus on neuroinflammatory mechanisms in Parkinson’s disease, a gap in the research portfolio in the current centers. The team will probe how the body’s immune system may contribute to the pathology seen in the brains of Parkinson’s disease patients and to the development and progression of the disease.

Only recently have researchers begun to suspect an important role for inflammation in the disease, and that is still largely uncharted territory. Research in this area could lead to therapies that can slow the progression or stop the disease mechanisms of Parkinson’s. This is a vital need since no such therapies exist.

The research requires a mix of specialized expertise from both neuroimmunology and neurodegenerative diseases. UAB scientists David Standaert, M.D., Ph.D., Etty “Tika” Benveniste, Ph.D., and Andrew West, Ph.D., are leading that team, bolstered by a two-year exploratory, P20 grant that NIH recently awarded to support preparation for a subsequent Udall P50 grant application.

Seeking synergy

“With centers, the NIH always looks for synergy,” said Standaert, who is professor and chair of the UAB Department of Neurology and has deep knowledge of neurodegenerative disease medical care and research, particularly Parkinson’s. “The hallmark of a center is the openness and willingness to work together. You have to be willing to share your ideas and frustrations, and share your opinions, in a back and forth manner. Everyone has to give up something, but they will find that the whole is greater than each part taken alone.”

Standaert was previously director of the then-Massachusetts General Hospital/MIT Udall Center before coming to UAB. Benveniste, professor and chair of Cell, Developmental and Integrative Biology (CDIB) at UAB, investigates the connections between the immune system and the brain. West, associate professor of neurology at UAB and co-director of the UAB Center for Neurodegeneration and Experimental Therapeutics, focuses on research exploring genetic causes of Parkinson’s disease, and he has previously trained at the Mayo Clinic Udall Center for Excellence, the then-UCLA Udall Center for Excellence and the Johns Hopkins Udall Center for Excellence.

They are adding critical team members from outside the Parkinson’s disease research field to the existing core of expertise in the neurology department. These include researchers Hongwei Qin, Ph.D., M.D., an associate professor in CDIB who has studied the immune response in neurological diseases like multiple sclerosis; Chander Raman, Ph.D., an immunologist who is a professor of medicine; and Stephanie Guthrie, CRNP, a nurse practitioner who will be vital in obtaining blood samples from Kirklin Clinic patients who are newly diagnosed with Parkinson’s disease. Ashley Harms, Ph.D., an instructor in neurology who trained in neuroimmunology, will be the scientific coordinator for the P20 grant.

David Standaert

Immune residents, or infiltrators?

In addition to solidifying this core collaboration team, the researchers are testing key hypotheses in two pre-clinical model systems. Both of these systems have been engineered to have elevated levels of clumped α-synuclein in their brains to provoke innate immune responses. These model systems can differentiate between the activation of brain-resident immune cells and the infiltration of immune cells from outside the brain. This will lay the groundwork for targeting some of the control systems of these immune responses for therapeutic benefit in the mouse models.

Thirdly, the team will develop a pipeline to human subjects — so researchers can obtain blood from patients newly diagnosed with Parkinson’s.

“We see about one to three patients a month with newly diagnosed Parkinson’s disease at the Comprehensive Parkinson Disease and Movement Disorder Clinic, which has 11 physicians, four nurses, two nurse practitioners and about 6,000 patient visits a year,” Standaert said. “We need to catch them in that window when they are just diagnosed, before any treatment. This would be difficult to do at a smaller center, but we’re big enough to do that.”

Fresh blood is needed to isolate monocytes, which are innate immune system cells that reside outside of the brain. The monocytes will be purified the same day the blood is drawn and immediately tested to see if they have been activated for an immune response. “We get patient blood samples at the clinic, take them to the lab and study them that afternoon,” Standaert said. “The number of places that can do that is pretty few.”

Standaert has been building collaborations with Benveniste’s group for several years, but the appearance of an NIH request for applications for the P20 grant a year ago jump-started a greater push. “That galvanized the effort to bring together a team to ask, what are the critical questions in the field, and how can we build a team to address these problems?”

“This collaboration is what UAB does well,” Standaert said. “The project takes existing strengths — the great clinical operation at UAB and the fantastic scientists in UAB labs — and welds them together.”

The title of the P20 grant is “Innate and Adaptive Immunity in Parkinson Disease.”

The Foundation for Mitochondrial Medicine, the University of Alabama at Birmingham and Seahorse Bioscience today announced the creation of the Foundation for Mitochondrial Medicine Program at UAB — a comprehensive clinical program for the diagnosis of neuromuscular mitochondrial diseases using precision medicine models for monitoring therapeutic interventions.

The shared academic, philanthropic and medical mission of the clinic is to revolutionize the treatment and diagnosis of mitochondrial diseases by establishing and integrating state-of-the-art techniques in bioenergetics and therapeutics using a precision medicine approach. The clinic plans to realize this vision by developing two parallel components: 1) a monthly multidisciplinary clinic to evaluate and care for adults and pediatric patients with mitochondrial disease and 2) a reference laboratory for metabolic bioenergetics focused on establishing mitochondrial-targeted clinical, noninvasive laboratory measurements and instruments.

“By establishing the clinic and sharing this vision, we plan to address the unmet clinical, diagnostic and therapeutic needs of the mitochondrial patient community,” said Laura Stanley, Executive Director of FMM. “Clinical needs of the patient community will be coordinated under one roof, and multiple specialists will join together to serve complex patient populations whose symptoms require the collective knowledge of neurologists, geneticists, gastroenterologists and others. UAB and Seahorse Bioscience have made revolutionary advancements in the field of bioenergetics, and UAB’s established research expertise and longstanding work in neuromuscular diseases make it the ideal location for the program.”

Mitochondrial disease can be caused by genetics and mutations to the mitochondrial or chromosomal DNA or can be acquired due to metabolic, aging or environmental stress. Despite significant advances in recognizing, diagnosing and treating patients over the last 40 years, there are still lacks of effective treatments that are targeted to the specific deficit in a patient. The precision instrumentation developed by Seahorse Bioscience and the bioenergetics testing from UAB will allow advances in metabolic and genetic analysis to be applied to the diagnosis and treatment of patients with mitochondrial disorders. Mitochondrial dysfunction is an underlying cause of many neurodegenerative diseases, cancer and cardiometabolic syndromes. From Parkinson’s to Alzheimer’s, diabetes and beyond, an understanding of mitochondrial stresses can lead to better treatments and quality of life for many.

fmm largeClick to enlargeUAB has a tradition of excellence in research and participation in clinical trials. UAB is also uniquely placed to advance the field of diagnostics, biomanufacturing systems and consumable labware products for biological research. Scientific expertise in mitochondrial medicine is longstanding at UAB and is available through a network of departments and the centers, especially the Center for Free Radical Biology. The UAB Mitochondrial Medicine Laboratory was established in 2011 in the Department of Pathology in the School of Medicine, and has been pioneering translational tests to assess mitochondrial function through noninvasive tests in human subjects.

“The most serious diseases that affect developed nations, such as atherosclerosis, neurodegeneration and diabetes, are known to involve changes in bioenergetic health,” said Victor Darley-Usmar, Ph.D., endowed professor of mitochondrial medicine and pathology, vice-chair for research in the UAB Department of Pathology, and scientific director of the program. “The challenge is to translate the findings in basic research in mitochondrial function and the pathology of disease to the clinic, and this program will be a major step toward achieving that aim. For the first time, we will apply new means of measuring bioenergetic health to the management and care of patients with mitochondrial diseases.”

Seahorse Bioscience developed the enabling technology upon which bioenergetics measurements, for the first time, can provide the necessary precision and reliability required to establish Clinical Laboratory Improvement Amendments (CLIA) tests for mitochondrial pathologies. Seahorse is the industry leader in metabolic analyzers and assay kits for measuring cell metabolism in live cells, in real time. XF Technology and stress test kits render the understanding and diagnosis of mitochondrial disease into a simple, efficient and user-friendly process, enabling researchers to understand better how bioenergetics regulates cellular function. Utilizing XF Technology and a bioenergetics stress test, researchers will measure and analyze respiratory complex activities and mitochondrial DNA damage in white blood cells and platelets from blood samples. This information will then form the basis of a Bioenergetic Health Index (BHI). The test is much easier to administer than a diagnostic muscle biopsy, and can effectively monitor the progression and response of patients to treatment. An important objective for the first three years of the UAB Program and Clinic will be to validate and provide CLIA certification for these tests using the XF platform.

“One of the keys to the resurgence in mitochondrial research and treatment has been our ability to redefine metabolism in the context of the complete cellular architecture of a living cell,” stated David Ferrick, chief scientific officer of Seahorse Bioscience. “Making this complexity addressable allows researchers and physicians to ask and answer questions that were out of reach, and thus limited them to theory and speculation. The combination of compelling patient advocacy by the FMM, basic and clinical expertise of UAB, and enabling technology from Seahorse will be the perfect storm for mitochondrial diseases."

Written by Jim Bakken
Director UAB, Media Relations