Brain Inflammation a Hallmark of Autism
While many different combinations of genetic traits can cause autism, brains affected by autism share a pattern of ramped-up immune responses, an analysis of data from autopsied human brains reveals. The study, a collaborative effort between UAB and Johns Hopkins, included data from 72 autism and control brains. It was published online in the journal Nature Communications.
“There are many different ways of getting autism, but we found that they all have the same downstream effect,” said Dan Arking, PhD, an associate professor in the McKusick-Nathans Institute for Genetic Medicine at the Johns Hopkins University School of Medicine. “What we don’t know is whether this immune response is making things better in the short term and worse in the long term.”
The causes of autism are a frequent research topic for geneticists. But Arking noticed that studies of gene expression involved too little data to draw many useful conclusions about autism. Unlike a genetic test, which can be done using nearly any cells in the body, gene-expression testing has to be performed on the specific tissue of interest; in this case, brains that could be obtained only through autopsies.
To combat this problem, Arking and his colleagues analyzed gene expression in samples from two different tissue banks, comparing gene expression in people with autism to that in controls without the condition. All told, they analyzed data from 104 brain samples from 72 individuals, the largest data set so far for a study of gene expression in autism.
While previous studies identified autism-associated abnormalities in cells that support neurons in the brain and spinal cord, the UAB-John Hopkins study was able to narrow in on a specific type of support cell known as a microglial cell, which polices the brain for pathogens and other threats. In the autism brains, the microglia appeared to be perpetually activated with the genes for inflammation responses turned on.
“This type of inflammation is not understood well, but it highlights the lack of current understanding about how innate immunity controls neural circuits,” said Andrew West, PhD, an associate professor in the UAB Department of Neurology and co-author of the study.
“Given the known genetic contributors to autism, inflammation is unlikely to be its root cause,” Arking said. “Rather, this is a downstream consequence of upstream gene mutation.” The next step would be to find out whether treating the inflammation could ameliorate symptoms of autism.
New Research Finds Baby’s Genes, Not Mother’s, May Trigger Some Preterm Births
Some babies may be genetically predisposed to being born too soon, and variants in the DNA of the fetus — not the mother — may be the trigger for some early births.
That is the finding of research conducted by Joseph Biggio, MD, professor and director of the UAB Division of Maternal-Fetal Medicine in the Department of Obstetrics and Gynecology, and his colleagues from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Genomics and Proteomics Network for Preterm Birth Research.
The March of Dimes will present its award for Best Research in Prematurity to Biggio for this work during the annual Society for Maternal-Fetal Medicine meeting in San Diego, California. Biggio’s research analyzed the number of copies of certain segments of DNA in the blood or saliva from hundreds of babies and their mothers.
“These findings open a whole different arena for us to look into as we think about preterm birth,” said Biggio, who was assisted by William Andrews, PhD, MD, professor in UAB’s Department of Obstetrics and Gynecology in UAB’s School of Medicine, and others. “It causes us to think more critically about the role of the fetus in causing preterm birth. We’ve always thought about preterm birth as a maternal issue, but these data change the paradigm. It may be the fetus who has the underlying predisposition, not the mother.
“This still is very preliminary, and more investigation is needed, but the research clearly identified genetic regions associated with an increased risk of preterm birth.”
No link was established between the number of copies of the mother’s genes and the risk of preterm birth. However, there was a two to 11-fold increase in preterm births before 34 weeks of gestation among infants in whom any of four genes was duplicated or any of seven genes was deleted.
“These findings may help explain what triggers early labor in some women even when they’ve done everything right during pregnancy and there’s no obvious cause for an early birth,” said March of Dimes Chief Medical Officer Edward R.B. McCabe, MD “The hope is that this finding may one day lead to a screening test to help identify which babies are at a higher risk of an early birth.”
The preterm birth rate in the United States dropped more than 10 percent between 2006 and 2013, with most of the improvement focused in late preterm births (those between 34 and 37 weeks of pregnancy). Today’s research findings focused on early preterm births — births before 34 weeks of pregnancy — in which there has been little improvement in recent years.
More than 450,000 babies are born too soon each year in the United States, and Alabama has one of the highest rates of preterm birth in the nation, at 15.1 percent. Preterm birth is the leading cause of newborn death, and babies who survive an early birth often face an increased risk of a lifetime of health challenges, such as breathing problems, cerebral palsy, intellectual disabilities and more. Even babies born just a few weeks early have higher rates of hospitalization and illness than full-term infants. It is a serious health problem that costs the United States more than $26 billion annually, according to the March of Dimes.
While the differences in the number of copies of the genes may not directly cause a preterm birth, they may make a baby more susceptible to infection or reacting to other harmful environmental factors that trigger early labor, Biggio says.
“We don’t know exactly that it’s the genes in these areas,” Biggio said. “It may be something else. But these changes are in the areas of these genes, and that’s certainly the first place to start looking.”
It may also help explain why treatment with progesterone, a naturally occurring hormone in pregnancy shown to prevent some preterm births, works for only about one-third of women.
“We think we are treating the mother with progesterone, but perhaps we are actually treating the baby or changing the fetal-immune response,” Biggio said.
The Eunice Kennedy Shriver National Institute of Child Health and Human Development funded this research, which Biggio says emphasizes the importance of genetics and informatics to scientific discovery. This also reinforces the importance of UAB’s investment in data infrastructure and its hiring of renowned expert James Cimino, MD as the inaugural director of the UAB Informatics Institute.
“Genetics and informatics are going to be a key to our understanding of complex disease, and preterm birth is a prime example,” Biggio said. “If we can begin to understand the complexity of preterm birth and can work to prevent it, we will be able to avert significant health care expenditures and morbidity.”
Danberry Issued CON To Add Memory Care Beds
The Alabama State Health Planning & Development Agency has issued a Certificate of Need to Danberry at Inverness to convert 24 Assisted Living Beds to Specialty Care Assisted Living beds.
“We have put a great deal of work into achieving the Certificate of Need,” said Danberry at Inverness Executive Director Jaclyn Gardner. “Now we look forward to following the required procedure for obtaining licensure. If successful, we hope to open a memory care unit by late 2015, which would fulfill the original intent of the assisted living component of Danberry at Inverness.”
Gandhi Joins Birmingham Infectious Diseases at Trinity
Trinity Medical Center is pleased to welcome Anurag Gandhi, MD, to its medical staff.
Anurag Gandhi, MD, who specializes in Infectious Diseases, has joined Birmingham Infectious Diseases, PC, in association with William Lapidus, MD, and Eima Zaidi, MD on the Trinity Medical Center campus.
Gandhi received his medical degree from St. John’s Medical College, Rajiv Gandhi University of Health Sciences in Bangalore, India. He completed his internal medicine residency at Upstate Medical Center, State University of New York in Syracuse, NY and his clinical infectious diseases fellowship at Strong Memorial Hospital, University of Rochester in Rochester, NY.
Gandhi is board certified in internal medicine and infectious diseases. He is an associate member of the Infectious Diseases Society of America, served as Chief of the Department of Medicine at Gadsden Regional Medical Center, and is a former board member of the Etowah County American Red Cross.
St. Vincent’s East Announces New Advisory Board Members
Joe Freeman, Bonnie Hicks, and Foster Ware III have joined the 11-member St. Vincent’s East Advisory Board.
Joe Freeman brings more than 10 years of financial experience and currently serves as the principal at his firm, E.F. Joseph, LLC. Freeman is involved in a wide range of community organizations, including Camp Smile-A-Mile and the Birmingham Irish Cultural Society.
Bonnie Hicks has more than 27 years of experience as realtor, currently working at Re/Max MarketPlace. She is involved in a variety of community organizations, including the St. Vincent’s Foundation Board, Eastern Women’s Committee of Fifty, and the Trussville Chamber of Commerce.
Foster Ware III has a diverse range of experience, including health care consulting, government affairs, sales management, and engineering. He is currently the area manager for the North Region of Alabama Power’s Birmingham Division.
UAB, Industry Partnership Could Lead to First Rapid Test for Bacterial Meningitis
Meningitis research efforts two decades in the making could soon come to fruition through a partnership between investigators at UAB and a medical device startup, with assistance from the UAB Institute for Innovation and Entrepreneurship.
Laboratory test results to diagnose this infection, particularly if bacterial meningitis is suspected, lose precious time and often are inaccurate, says Scott Barnum, PhD, professor in the UAB Department of Microbiology.
“Viral meningitis generally is not serious and often is treated symptomatically, while bacterial meningitis requires immediate intervention and treatment with antibiotics because of the serious nature of that infection,” Barnum said.
Yearly in the United States, from 2003-2007, about 4,100 cases of bacterial meningitis occurred, resulting in 500 deaths, according to the Centers for Disease Control and Prevention.
Barnum’s work with bacterial meningitis dates back 20 years, when his team was looking at production in the brain of proteins in the complement system, a critical part of the immune system. They found that many complement proteins were produced by several cell types in the central nervous system, including neurons.
“When we looked at the levels of complement proteins in the cerebrospinal fluid of patients with confirmed bacterial meningitis, we found that certain proteins were markedly elevated compared to the levels found in aseptic meningitis (meningitis caused by a virus or other pathogen),” Barnum said. “We patented this observation with the aim of developing a diagnostic test for discriminating between the two types of meningitis.”
Now Barnum’s team has partnered with Kypha Inc., a St. Louis-based company focused on complement proteins and lateral flow assays, which are diagnostic tests similar to a pregnancy test, to bring that goal to a reality.
“A test that could rapidly discriminate between bacterial and viral meningitis would be a valuable tool for the emergency room physician,” Barnum said. “We would love to see the test be used in underdeveloped parts of the world where limited resources prevent timely and accurate diagnosis of most diseases. This is the kind of test we are working to develop in partnership with Kypha.”
With Kypha’s help, Barnum says the original scope of the project has expanded and opened other doors at UAB that have led to new collaborations that are mutually beneficial. Kypha has funded Barnum’s postdoctoral researcher, Theresa Ramos, PhD, dubbing her a postdoctoral entrepreneur for the company.
“This is a unique position that Kypha developed. Postdocs like Dr. Ramos will spend 50 percent of their time in the lab and 50 percent of their time learning about the business side of science through interaction with Kypha,” Barnum said. “This is a great opportunity for someone thinking about moving into biotechnology or pharmacology after their postdoc. For Dr. Ramos, this will be a great experience and will significantly enhance her resume.”
“After Kypha CEO Chad Stiening visited UAB and witnessed the breadth of research and collaborations that occur here, he and his team decided to make UAB a beta-testing site for their new device, the COMP ACT System,” Ramos said. “It has been a match made in research-entrepreneurial heaven.”
Stiening says they were impressed with UAB’s clinical research infrastructure, and with the level of responsiveness of faculty, clinical staff and administrative leaders.
“This was important given the broad potential clinical utility of Kypha’s products and our desire to conduct several clinical studies in parallel across multiple indications,” Stiening said. “Perhaps the most pleasant surprise was the level of institutional support for industry partnerships — and a recognition of the value and unique challenges that startups bring to the equation.”
Several layers of support exist for this project at UAB, says Ramos, including the Department of Microbiology, UAB Hospital’s Emergency Department, the Institutional Review Board, and most notably the Institute for Innovation and Entrepreneurship.
“We couldn’t move our project forward without the help of the IIE and Kypha. The speed and scale of what we can do with the partnership take the effort to a whole new level,” Barnum said. “It’s a synergy that all universities and biotech startups could benefit from. I hope that it is the first of many partnerships that UAB and the IIE develop.”
IIE Managing Director Kathy Nugent, PhD says the IIE is the nexus for UAB innovation and applied research.
“Our mission is to broaden the impact of UAB’s contributions by facilitating collaboration with industry and providing greater opportunities for researchers and entrepreneurs,” Nugent said. “UAB is at the forefront of scientific and medical innovation, and Dr. Barnum’s research is an excellent example of the game-changing breakthroughs that the IIE is helping to bring forward.”
Nugent says the IIE is excited to be working with researchers like Barnum, and they are committed to ensuring that the public has ongoing access to the newest, most effective scientific and health care innovations, products and procedures.
“We are fortunate to be located in Birmingham with such a vibrant academic and medical ecosystem to support this type of innovation,” Nugent said.
“We have been very fortunate to have the support of the IIE, my chairman, Frances Lund, PhD and Kypha as well,” Barnum said. “It’s a great validation of our original basic science and in our plans to develop this finding into a rapid, point-of-care test that we hope will have worldwide clinical utility.”
BCRFA Donates to UAB Cancer Center
The Breast Cancer Research Foundation of Alabama presented $650,000 — its largest donation to date — to the UAB Comprehensive Cancer Center, for a total exceeding $5.1 million since BCRFA’s inception in 1996.
“We are thankful for this generous gift. Without the help of the community, none of this would be possible,” said Edward Partridge, MD, director of the UAB Comprehensive Cancer Center.
Hrynkiw Is a National Community All Star
Zenko Hrynkiw, MD is a 2014 Healthcare Community All Star, an award given by Safety National, a provider of excess workers’ compensation coverage to self-insured employers nationwide. Each year, Safety National names three Community All Stars who have done something extraordinary in terms of philanthropy or acts of kindness.
Alabama Retail Comp, the workers’ compensation fund that serves Alabama Retail members, nominated Dr. Hyrnkiw for the heroic efforts he made during the debilitating snow storm that hit Birmingham in January 2014, bringing the city to a standstill. Realizing he would be unable to travel by car, Hrynkiw walked more than six miles through the snow and ice to Trinity Medical Center to perform emergency surgery on a patient with a traumatic brain injury.
Each Community All Star category winner is awarded $10,000 in the form of a scholarship endowment or donation to a charity of his or her choice. Hrynkiw requested the donation on his behalf go to Operation Smile, which performs cleft lip and cleft palate surgeries on children.
UAB Named to National Pulmonary Fibrosis Care Network
UAB has been added to the Pulmonary Fibrosis Foundation Care Center Network as part of a major expansion of that network. The PFF Care Center Network, which now boasts 21 sites in 20 states, comprises the leading medical centers with specific expertise in treating interstitial lung diseases and pulmonary fibrosis, a group of lung disorders including idiopathic pulmonary fibrosis (IPF), that often are difficult to manage and that are associated with survival rates of less than five years following diagnosis in certain diseases.
The UAB Division of Pulmonary, Allergy and Critical Care Medicine, under the leadership of division director Victor Thannickal, MD, has become a leading research and clinical care site for pulmonary fibrosis. The division’s research programs include multiple NIH-funded grants that have grown to almost $4 million per year. The Interstitial Lung Disease clinic in The Kirklin Clinic now follows as many as 500 patients, with an estimated 200 new patients per year.
Kinney is President-Elect of the Jefferson County Medical Society
F. Cleveland Kinney, PhD, MD is the new President-Elect of the Jefferson County Medical Society.
Kinney, who serves as Professor Emeritus of Psychiatry and Behavioral Neurobiology at UAB, attended UAB to earn his PhD in anatomy in 1976 and his medical degree in 1985, and joined the UAB Hospital as a staff psychiatrist in 1990 after completing his psychiatry residency and fellowship in geriatric psychiatry at UAB.
In 1968, after earning his BA at Birmingham-Southern College, Kinney joined the U.S. Navy and was stationed at Headquarters Allied Forces Northern Europe in Oslo, Norway until his honorable discharge in 1972.
Kinney, who has been listed in the Best Doctors in America, has been chosen for a number of honors, including the Exemplary Psychiatrist Award from the National Alliance for the Mentally Ill; an Argus Society Award for Excellence in Teaching; and Outstanding Faculty Teacher by the UAB Psychiatry Residents Association.
He finds that his academic training in both anatomy and psychiatry work hand-in-hand when looking at MRI scans to determine whether brain lesions are correlating with changes in geriatric patients’ behavior.
In his new role with the Jefferson County Medical Society, Kinney hopes to raise money for local medical school scholarships.
Heslin Elected Chief of Staff at UAB Hospital
Martin J. Heslin, MD, Chief of the Section for Surgical Oncology at UAB and Senior Scientist at the UAB Comprehensive Cancer Center, has been elected for a five-year term as Chief of the Medical Staff at UAB Hospital. Heslin is also the Associate Director of Clinical Programs at the Comprehensive Cancer Center.
Heslin has been on UAB’s staff since 1996 after completing his post graduate training at Memorial Sloan-Kettering Cancer Center and NYU Medical Center. He specializes in the research and treatments of gastrointestinal cancers and soft-tissue sarcomas. He is the director of the Multidisciplinary Gastrointestinal Oncology Clinic, which was created to provide all gastrointestinal cancer patients with a multidisciplinary approach to the treatment of their disease.
