Postdocs in UAB News

  • UAB Psychology professor given early career award
    Faculty member honored for significant contributions to the field.

    Despina Stavrinos, Ph.D., has been selected to receive the Routh Early Career Award from the Society of Pediatric Psychology.

    This national award recognizes an early career member of the society who has made significant contributions to the field of pediatric psychology in research, clinical training and service.

    Stavrinos, an assistant professor in the College of Arts and SciencesDepartment of Psychology, studies distracted driving, with particular attention to at-risk populations.

    She serves as the director of the Translational Research for Injury Prevention, or TRIP, laboratory. The focus of the lab’s research is the prevention and control of unintentional injuries that result from motor vehicle crashes.

    The TRIP lab offers students at various levels of training, from high school to postdoctoral, and from various disciplines the opportunity to conduct high-quality behavioral research. Since its establishment in 2009, nearly 100 students have been trained under Stavrinos’ mentorship.

    The award will be presented at the Society of Pediatric Psychology’s annual conference in April.

  • UAB researchers work to unravel the complex genetic disease neurofibromatosis type 1
    One major goal is the discovery of new genotype/phenotype correlations — how a particular mutation indicates that some symptoms in patients are unlikely to develop with age.
    Ludwine Messiaen

    It is easy to tell a medical research story that has a simple and dramatic moment. But disease is often much more complex, and the work to understand it can be painstaking.

    A vivid example of that is seen in the UAB Medical Genomics Laboratory, headed by Ludwine Messiaen, Ph.D., professor of genetics. This lab offers clinical genetic testing for a broad array of common and rare genetic disorders. One of the most confounding is neurofibromatosis type 1.

    This can be a heartbreaking disease.

    Changes at puberty

    It usually starts with café-au-lait skin markings, so named because of their distinctive coloring, in an infant. But at puberty — already a challenging time in a person’s life, many patients develop benign skin tumors called neurofibromas that erupt as bumps across the body. Patients vary widely in their symptoms, which can include freckles near skin folds of the body, nodules in the eyes, tumors along the optic nerve, heart defects, anomalies of connective tissue or bones, developmental delay, intellectual disability, and learning problems.

    Patients show a broad clinical variability as they grow, and whether their case will be mild or severe cannot — in most cases — be predicted when the disease first appears. This leaves physicians and families uncertain about what symptoms will appear in a particular child as he or she nears puberty.

    Cafe-au-lait skin markings on the back of a young child

    Profusion of mutations

    This kaleidoscope of clinical signs is mirrored by an abundance of different mutations in the NF1 gene, responsible for the disease. The UAB Medical Genomics Laboratory has collected DNA and identified a pathogenic mutation in more than 7,800 unrelated neurofibromatosis type 1 patients. All have NF1 mutations, but meticulous examination has revealed so far more than 3,000 different mutations. These can be found in every part of the gene, and the mutational spectrum involves microdeletions, deletions or duplications that involve one or more exons, frameshift and nonsense mutations, and splice or missense mutations. Almost half of the NF1 patients carry a unique mutation found only in their specific family. Other mutations have been found in multiple unrelated families.

    Two searches

    From this complicated array of mutations and clinical symptoms, Messiaen and her colleagues have tried to answer two questions.

    First, can a particular mutation be correlated with the symptoms that will develop as the child grows? This is called a genotype/phenotype (DNA/symptoms) correlation, and only two have previously been found for neurofibromatosis type 1.

    “It’s important for people to know what may happen,” Messiaen said. “When a child is born with neurofibromatosis type 1, café-au-lait spots appear very shortly after birth; but other problems, more specifically the development of skin neurofibromas, typically appear around puberty. If a genotype/phenotype correlation exists for a particular mutation, it will help these families have some perspective of what the future will bring, and it will help families cope with the disease. If it is a mutation that takes away the heavy tumor burden at puberty, that information will relieve families, even though learning disabilities may still appear.”

    The second question for Messiaen and UAB postdoctoral trainee Meng-Chang “Jack” Hsiao, UAB Department of Genetics, is whether they could identify the likely mechanism that caused a group of mutations in which the DNA has been rearranged to create mix-ups that make the gene longer or shorter.

    Each question requires meticulous research. One means reaching out to patients, families and referring physicians around the nation and the world. The other is a molecular genetic detective story, pursued in the UAB lab.

    Messiaen and Meng-Chang "Jack" Hsiao are exploring the mechanisms behind the mutations seen in neurofibromatosis type 1.

    Seeking a correlation

    For the first question, Messiaen last year led a group of 74 researchers and clinicians from 58 centers in the discovery of just the third genotype/phenotype correlation ever found for neurofibromatosis type 1. They looked at 136 individuals who all had a missense mutation in the arginine moiety of neurofibromin, the protein encoded by the NF1 gene, at amino acid position 1,809. These mutations are the second-most-frequent ones seen in the UAB collection.

    To look for a correlation, the team had to gather detailed clinical symptomatic information for each of the neurofibromatosis patients, from patients, families, referral physicians and researchers in 24 U.S. states and Australia, Belgium, Brazil, Chile, the United Kingdom, India, Israel and Spain.

    In a paper published in the journal Human Mutation last year, they found that these patients have a distinct phenotype, Messiaen says. They had the café-au-lait marks, with or without the skin-fold freckling and Lisch eye nodules. But the patients did not develop the visible, disfiguring neurofibromas on their skin around puberty. However, there was a higher prevalence of blood flow obstruction from the heart to the lungs and a short stature. More than half had developmental delays and/or learning disabilities.

    Messiaen is calling for international collaboration to expand the study to a total of 250 mutations, which will provide the statistical power needed for patient case management by doctors. And in the next few years, she will focus on finding more genotype/phenotype correlations for other specific mutations.

    "If a genotype/phenotype correlation exists for a particular mutation, it will help these families have some perspective of what the future will bring, and it will help families cope with the disease."

    "If a genotype/phenotype correlation exists for a particular mutation, it will help these families have some perspective of what the future will bring, and it will help families cope with the disease."

    Chasing molecular clues

    For the second question, Hsiao, Messiaen and colleagues looked at NF1 copy-number variations — where the mutant gene is either longer or shorter than a normal NF1 gene — from 85 unrelated neurofibromatosis type 1 patients, along with two previously published copy-number variations. Ten of these were partial duplications within the NF1 gene, and 77 were deletions. Hsiao looked for specific nucleotide breakpoints in these variants — the places where the duplication or deletion begins or ends — that would be clues to how the changes occurred.

    The methods to examine these mutant genes include multiplex ligation-dependent probe amplification, array comparative genomic hybridization, breakpoint-spanning PCR and sequencing.

    “The most difficult challenge is to see how the rearrangements happen,” Hsiao said. “It’s really difficult to decipher.”

    In a paper published in The American Journal of Human Genetics last year, Hsiao found that DNA replication-based mechanisms — such as fork stalling and template switching, and microhomology-mediated break-induced replication — as well as serial replication stalling appear to be the major causes of the NF1 copy-number variants. In one complicated rearrangement, the DNA replication appeared to have stalled five times, with the stalled DNA strand then either invading forward or invading backward into another part of the NF1 gene. Hsiao also found that the mutant genes showed rearrangement hotspots that included one palindromic sequence and four Alu elements. Alu elements are short primate-specific repeats in the DNA; the human genome contains about 1 million copies of various Alu elements that make up almost 11 percent of the genome.

    Two sides to the research

    Messiaen says the two recent papers are “nice companions.”

    “They show two sides of research aspects of this laboratory,” she said. “One digs deeper into the mechanism of specific types of mutation, and one contributes to genotype/phenotype correlation.”

  • 2016 Darwin Day commemorates Charles Darwin’s birthday, showcases scientific research
    Poster sessions and guest lecturers aim to celebrate Darwin’s legacy.

    To honor the 207th birthday of legendary evolutionary biologist Charles Darwin, the University of Alabama at Birmingham will host its annual Darwin Day on Thursday, Feb. 11, and Friday, Feb. 12. The events will celebrate scientific research in evolutionary biology and other disciplines.

    The event is co-hosted by UAB’s departments of Anthropology and Biology in the College of Arts and Sciences.

    “Charles Darwin’s great discovery, the principle of natural selection, is more relevant to science than ever before,” said Steven Austad, Ph.D., chair of the Department of Biology. “For instance, it underlies our increasing success in cancer chemotherapy, provides guidance in combating new strains of drug-resistant diseases, and will ultimately determine how catastrophic climate change will prove to be for our planet.”

    A panel discussion exploring evolution, belief and education will kick off this year’s Darwin Day events in Lister Hill Library’s Edge of Chaos.The panel, which will be led by guest speakers Elisabetta Palagi, Ph.D., a behavioral biologist from the Natural History Museum University of Pisa in Italy, and Josh Rosenau, an evolutionary biologist from the National Center for Science Education, will take place from 2-3:30 p.m. on Feb. 11. Lee Meadows, Ph.D., from UAB’s School of Education, and Marshall Abrams, Ph.D., a philosophy professor in UAB’s College of Arts and Sciences, will also be panelists for this discussion.

    Following the panel, students and faculty will present a public poster session highlighting exciting new research from 3:30-4:30 p.m. at the Edge of Chaos. Those interested in presenting a poster should send an email to darwinday@uab.edu with their name, department, poster title, and indication of whether they are a student, postdoc or faculty.

    “Anthropologists and other students of science today will be well-served by striving to emulate Darwin’s objectivity, meticulous attention to detail and appreciation for complexity during the practice of science.”

    On Thursday evening, Darwin Day activities will continue with a reception followed by a talk by Rosenau. Rosenau’s lecture, “The Impact of Darwin in Everyday Life,” will begin at 7 p.m. following the 6 p.m. reception at the McWane Science Center and is open to the public.  

    Darwin Day will continue on Friday, Feb. 12, from 4 to 5 p.m., with a lecture from Palagi. Palagi’s talk, “The Strategic Functions of Play: Modality and Communication,” will be held in Heritage Hall, Room 104.

    “The approach of Charles Darwin represents the scientific endeavor at its best wherein data and reasoning interact to elucidate the natural world,” said Doug Fry, Ph.D., chair of the Department of Anthropology. “Anthropologists and other students of science today will be well-served by striving to emulate Darwin’s objectivity, meticulous attention to detail and appreciation for complexity during the practice of science.”

    Refreshments and drinks will be provided at all events, and Darwin Day T-shirts will be on sale as well. For more information about the events, email darwinday@uab.edu.

    Sponsors for the 2016 Darwin Day include the UAB Honors College and the Endowment for the John S. Jemison, Jr., Visiting Professorship in the Humanities.

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UAB Research News

  • Researchers studying the effects of new HIV-prevention method in postpartum, lactating women
    UAB is recruiting postpartum women who are still lactating, for a study on the effects of the antiretroviral drug used to prevent HIV transmission.

    A new study at the University of Alabama at Birmingham School of Medicine’s Alabama Microbicide Clinical Research Site is looking at postpartum, lactating women’s absorption level of an antiretroviral drug called dapivirine. The drug is delivered via a vaginal ring and may help prevent HIV transmission.

    “The use of intravaginal rings containing anti-HIV drugs, like dapivirine, is being widely studied as a female-controlled option to protect against the sexual transmission of HIV,” said Craig Hoesley, M.D., senior associate dean and chair for Medical Education at UAB. “As part of this process, we need to make sure these agents are safe for women, including women who have recently given birth and are breastfeeding.”

    UAB is one of two sites conducting the study in conjunction with the Microbicide Trials Network. Researchers are looking for eight women who have weaned their infants of breast milk, but are still lactating. Participants will continue to pump for two weeks while wearing the dapivirine vaginal ring. Researchers will look at the level of dapivirine in the breast milk to determine if the vaginal ring is safe for a woman to wear while breastfeeding and if the level of drug in the breastmilk is safe for an infant..

    This study is part of ongoing research of the dapivirine vaginal ring, developed for healthy people to use to prevent transmission of HIV in the event they are exposed.

  • Anal sex linked to increased risk of incontinence in both males, females
    Study published in the American Journal of Gastroenterology shows fecal incontinence risk from anal sex is heightened for both women and men, with men almost three times as likely to experience incontinence.

    Engaging in the practice of anal sex may increase risks for bowel problems, including fecal incontinence and bowel leakage, according to a University of Alabama at Birmingham Department of Medicine study published in the American Journal of Gastroenterology.

    The incontinence risk is heightened particularly among men who have sex with men, according to lead author Alayne Markland, D.O., associate professor in the Division of Gerontology, Geriatrics and Palliative Care in UAB’s School of Medicine. The researchers analyzed data from the 2009-2010 National Health and Nutrition Examination Surveys from 6,150 adults. They found 37 percent of women and almost 5 percent of men reported trying anal intercourse at least once. Women engaging in anal sex were 50 percent more likely than their peers to report having fecal incontinence at least once a month. The men’s odds of incontinence were almost tripled.

    “The study did not provide data on the frequency of the practice of anal sex and the impact of incontinence, but it did show a relationship between the practice of anal sex and fecal incontinence — more so among men than women,” Markland said. “What we don’t know is whether someone who has anal sex one or two times is at the same increased risk for fecal incontinence as someone who has anal sex regularly.”

    Overall, 4,170 adults ages 20-69 (2,070 women and 2,100 men) completed sexual behavior questionnaires and responded to fecal incontinence questions as part of the NHANES surveys. Overall, 8.3 percent of women and 5.6 percent of men in the study had fecal incontinence. Fecal incontinence rates were higher among women (9.9 percent) and men (11.6 percent) reporting anal intercourse than among women (7.4 percent) and men (5.3 percent) not reporting anal intercourse.

    Fecal incontinence was determined to have occurred by researchers who reviewed responses to survey questions about leakage of mucus, liquid or stool and occurred at least monthly. The study showed that most adults who experience fecal incontinence have only occasional bouts of diarrhea. However, fecal incontinence can be chronic; it is often caused by muscle and nerve damage around the rectum, constipation, certain diseases, surgical procedures, and childbirth.  

    Markland says previous clinical trials have shown that pelvic floor muscle or anal exercises can be an effective treatment for fecal incontinence, and she recommends those engaging in anal intercourse consider these exercises to help guard against decreased anal sphincter tone.

    Markland says little is known about how anal intercourse might affect bowel function, even though the survey showed the practice is common among both heterosexual and homosexual couples.

    “We really know very little about the connection between anal sex and fecal incontinence, especially among women,” Markland said. “Older studies among predominately HIV-positive males showed that men who have sex with men may have impaired rectal muscle strength. But one thing I think this study does show is that it is important that both the patient and clinical provider need to be aware of the potential risks associated with anal incontinence and be willing to discuss what those risks may be.”

    Markland says previous clinical trials have shown that pelvic floor muscle or anal exercises can be an effective treatment for fecal incontinence, and she recommends those engaging in anal intercourse consider these exercises to help guard against decreased anal sphincter tone.

    “These are also known as Kegel exercises,” Markland said. “But, doing these exercises has not been studied as a preventive measure for lowering the odds of having fecal incontinence in a general population. All we can do is speculate.”

    Markland maintains an NHANES data set, and her primary research interest is in incontinence, specifically bowel leakage. She completed the study using indirect funding from several grants.

    “I am always looking for potentially modifiable factors that may be related to bowel leakage,” Markland said. “Anal intercourse has been understudied in our population in general, and anal incontinence and bowel incontinence were evaluated only in men who have sex with men in older studies. I thought we really needed to look at both men and women and assess the prevalence and associations between anal intercourse and fecal incontinence in both genders.” 

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