Program Co-Directors:

Doug Ayers, Ph.D.
dayers@uab.edu

Lisa Schwiebert, Ph.D.
lschwieb@uab.edu

The mission of the Business Certificate Program in Life Sciences Entrepreneurship is three-fold:

  • To provide knowledge in the areas of business and entrepreneurship to UAB graduate students, Postdocs, and faculty
  • To further cross-institutional collaborations among UAB schools
  • To promote interactions between UAB and the Birmingham business community

The program includes three required courses in Business Planning (MBA 673), Understanding the Biotech Industry (MBA 681), and Innovation (MBA 690).  Each of these courses is 3 credit hours. There are no pre-requisites and these courses may be taken in any order.

Current UAB graduate students may register directly.  If you are not a current graduate student, you will need to apply to the UAB Graduate School as a non-degree seeking student. Non-degree seeking students will need to contact Christy Manning at (205) 934-8815 or cmanning@uab.edu for more information.
 

Postdocs in UAB News

  • 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.

  • How obesity makes memory go bad
    UAB researchers find that epigenetic changes associated with chronic obesity alter expression of memory-related genes in the brain.

    J. David Sweatt, Ph.D.University of Alabama at Birmingham researchers are probing how obesity makes memory goes bad, and the underlying molecular mechanism that drives this decline.

    They have found that epigenetic changes dysregulate memory-associated genes, and a particular enzyme in brain neurons of the hippocampus appears to be a link between chronic obesity and cognitive decline. Their work is published in the Jan. 27 issue of Journal of Neuroscience.

    Obesity plagues developed nations, and among the numerous negative health outcomes associated with obesity is a memory impairment that is seen in middle-aged and older obese people. The cause of this decline? Experiments with obese rodents have given a clue: altered gene expression in the hippocampus area of the brain. Until now, the reasons gene expression was changed, as well as the mechanism by which obesity leads to pathogenic memory impairment, have not been known.

    There was one suspect: epigenetic dysregulation in neurons of the hippocampus. Foundational experiments over the past decade have linked the creation of long-term memories to changes in DNA methylation and hydroxymethylation — changes caused by epigenetic mechanisms that sit above the level of the genes.

    Such lasting molecular changes to DNA appear to play an important role in promoting or suppressing memory formation through their ability to increase or reduce the expression of genes that help brain neurons create new synaptic connections.

    UAB researchers have now shown that epigenetic changes are indeed associated with changes in the expression of memory-associated genes within the hippocampus of obese mice, and these epigenetic changes correlate with diminished object location spatial memory in the obese mice. The UAB researchers have also implicated reduced amounts of one particular memory-associated gene product — SIRT1 — as the principal pathogenic cause of obesity-induced memory impairment. The hippocampus subregion of the brain is important for consolidation of long-term memory.

    Obesity and cognitive decline

    Evidence that suggests a link between the two includes:

    • People aged 40-45 who were obese had a 74 percent increased risk of dementia 21 years later; and those who were overweight had a 35 percent greater risk. This study cohort had 10,276 men and women. Whitmer, RA, et al., BMJ 2005.
    • A study of 2,223 healthy workers found that a higher body-mass index was associated with lower cognitive scores, after adjustment for age, sex, educational level, blood pressure, diabetes and other co-variables. Also, a higher BMI at baseline was associated with higher cognitive decline at a follow-up five years later. Cournot, M., et al., Neurology 2006.
    • Metabolic syndrome in 73 people with an average age of 60 was associated with significant reductions in recall and overall intellectual functioning, compared with age- and education-matched controls. Hassenstab, J.J., et al., Dementia and Geriatric Cognitive Disorders 2010.
    • A study of 8,534 twin individuals who were 65 or older showed that being overweight or obese at mid-life, with an average age of 43, was related to later dementia at the older age. Xu, W.L., et al., Neurology 2011.

    Corresponding author J. David Sweatt, Ph.D., first author Frankie D. Heyward, Ph.D., and colleagues in the UAB Department of Neurobiology, Evelyn F. McKnight Brain Institute, write that these data “provide the first evidence that high-fat-diet-induced obesity leads to the time-dependent development of aberrant epigenetic modifications within the hippocampus, as well as corresponding reduction in the expression of various memory-related genes.”

    Sweatt noted, “We feel this is a very exciting finding that identifies a new linkage between diet, epigenetics and cognitive function, especially in light of the burgeoning obesity epidemic in the U.S. and elsewhere.”

    This work, they write, “offers a novel working model that may serve as a conceptual basis for the development of therapeutic interventions for obesity-induced memory impairment.”

    In details about the cause of altered gene expression, the UAB researchers found that:

    • Mice with diet-induced obesity at 20 weeks had impaired performance in object location memory tests, and their hippocampus had impaired synaptic plasticity, as measured by long-term potentiation.
    • Four memory-associated genes — Ppargc1a, Ppp1cb, Reln and Sirt1 — showed significantly decreased gene expression at 23 weeks of diet-induced obesity, as has been seen before, and the latter three had significantly increased DNA methylation in their gene promoter regions. Increased methylation is known to decrease gene expression. Furthermore, the Sirt1 promoter region also had significantly decreased DNA hydroxymethylation. Gene expression increases or decreases as DNA hydroxymethylation increases or decreases.
    • Obesity-induced memory impairment develops over time. At just 13 weeks of diet-induced obesity, seven weeks earlier than the experiments above, mice did not have significant object location memory impairment, and at 16 weeks of diet-induced obesity, also seven weeks earlier than above, none of the genes showed significant increases in DNA methylation. Only one gene at 16 weeks — Ppargc1a — showed significant decreases in gene expression and DNA hydroxymethylation.

    To probe the mechanism by which obesity leads to pathogenic memory impairment, the UAB researchers focused on the gene Sirt1, which makes an enzyme that is active in the neuron during energy expenditure and fat mobilization. This enzyme appears to be depleted and dysfunctional in obesity, and the deletion of the Sirt1 gene in the brain shortly after birth is known to impair memory and the ability to form new neural synapses. These roles for the SIRT1 gene product — in both high-fat-diet-induced molecular pathology and in memory impairment — suggest that it might be a link between chronic obesity and cognitive decline.

    Frankie Heyward, Ph.D.Heyward, Sweatt and colleagues found that the hippocampus of obese mice had significantly diminished protein expression of SIRT1, and a substrate of the enzyme, acetlylated-p53, was significantly increased, suggesting reduced enzymatic activity. Also, a targeted deletion of Sirt1 in the forebrain region that includes the hippocampus at age 8-12 weeks showed decreased Sirt1 mRNA and protein in the hippocampus, and these mice showed impaired object-location memory when tested two weeks later.

    Furthermore, chemical activation of SIRT1 in diet-induced obese mice by feeding them resveratrol showed decreased levels of acetylated-p53, suggesting increased SIRT1 enzymatic activity, and the resveratrol-fed obese mice had a normal object-location memory, as compared with the control obese mice. The resveratrol-fed obese mice did not show an enhanced memory compared with normal mice. This suggests that resveratrol preserved their hippocampus-dependent spatial memory and SIRT1 function in the hippocampus.

    Besides Heyward and Sweatt, co-authors of the paper, “Obesity weighs down memory through a mechanism involving the neuroepigenetic dysregulation of Sirt1,” are Daniel Gilliam, Mark Coleman, Cristin Gavin, Ph.D., Jing Wang, Ph.D., Garrett Kaas, Ph.D., Richard Trieu, John Lewis and Jerome Moulden, all of the UAB Department of Neurobiology.

    Heyward is now a postdoctoral fellow at Harvard Medical School, the Broad Institute and Beth Israel Deaconess Medical Center. While at UAB, Heyward was supported by a UNCF/Merck Graduate Science Research Dissertation Fellowship that helps train and develop African-American biomedical scientists.

    About 10 years ago, Sweatt’s lab made the seminal discovery that everyday experiences tap into epigenetic mechanisms in subregions of the brain, and the resulting epigenetic changes in DNA are critically important for long-term memory formation and the stable storage of long-term memory. The 2007 Neuron paper “Covalent modification of DNA regulates memory formation,” by Courtney Miller, Ph.D., and Sweatt, was the first to show that active regulation of the chemical structure of DNA is involved in learning and experience-driven changes in the brain.

    This work was supported by National Institutes of Health grants T32HL105349, MH57014, P60DK079626 and P30DK56336. The T32 pre-doctoral fellow grant to Heyward from the UAB Nutrition and Obesity Research Center supported his training in the biological basis of obesity.

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UAB Research News

  • UAB awarded Gates Foundation Grand Challenge awards to address maternal-fetal health in South Africa
    UAB receives two grants from the Gates Foundation to address pregnancy-related problems in developing countries.
    Written by Kendra Carter
    Media contact: Bob Shepard, bshep@uab.edu

    The University of Alabama at Birmingham School of Medicine is partnering with researchers at Sefako Makgatho Health Sciences University in Pretoria, South Africa, to address pregnancy-related problems in developing countries, funded by two $2.5 million grants from the Bill & Melinda Gates Foundation.

    The Gates Foundation’s All Children Thriving initiative received 54 letters of intent — or preliminary applications for funding — in the current funding round. UAB investigators submitted five of the 54. The All Children Thriving initiative focuses on creating new tools and methods that ensure safe, healthy births for both infants and mothers.

    Rubin Pillay, M.D., Ph.D., assistant dean for global health innovation at the UAB School of Medicine and professor of health care innovation and entrepreneurship in the UAB Collat School of Business, says nine proposals — including three from UAB — were invited to make full submissions. “Of those, three grant awards were made, and UAB received two,” he said.

    In the first project, UAB researchers are looking to develop a low-cost, one-time blood test for gestational diabetes, a disease that increases the risk of birth injury, cesarean delivery and stillbirth and has lifelong adverse health consequences for both mothers and infants. Currently, the diagnosis of gestational diabetes relies on glucose tolerance testing, which is expensive and time-consuming to administer. UAB researchers are working to develop an improved diagnostic method that is reproducible, inexpensive, requires only one blood draw, and can be performed at a wide range of gestational ages.

    Doctors and researchers at Sefako Makgatho Health Sciences University will recruit pregnant South African women at 20 to 28 weeks pregnant who will be screened for gestational diabetes with routine glucose tolerance testing. Metabolomics analyses, an innovative technology that can measure thousands of analytes simultaneously, will be performed to identify unique biomarkers of gestational diabetes, insulin resistance and hyperglycemia. Researchers will then identify the biomarkers with the greatest sensitivity and specificity for gestational diabetes and combine them into a single test.

    The second project aims to develop an easy-to-use and cost-effective cervical pessary — a device placed at the opening of the cervix to close it — with sensors to detect and prevent preterm labor. In South Africa, approximately eight out of every 100 infants are born prior to 37 weeks of gestation, according to Pillay. This amounted to approximately 84,000 preterm births in South Africa in 2011.

    “These projects give UAB the opportunity to partner with a new medical school in South Africa for truly innovative research that could have a transformative impact on the lives of women and children in developing areas. The fact that we received two of the three project awards shows our competitiveness in patient-centered research and highlights our successful efforts to increase UAB’s impact on global health care delivery.”

    A short cervical length is one of the best predictors of subsequent, spontaneous preterm birth. Pillay says the two best interventions to prevent preterm birth are the use of vaginal progesterone and the placement of a cervical pessary, but significant barriers to care in developing countries — such as access to needed medical equipment and patient compliance — limit effectiveness and success of the treatments. The UAB pessary would have sensors to detect preterm labor that link to a mobile phone to alert women of cervical shortening and dilation and would also contain progesterone, which would be administered directly to combat cervical shortening.

    Pillay says the research and development effort is a multidepartment, multischool collaboration across UAB and includes the Department of Pharmacology and Toxicology and the Department of Obstetrics and Gynecology in the School of Medicine; the School of Engineering; the Department of Computer and Information Science in the College of Arts and Sciences; and the Department of Biomedical Engineering, a joint department in the Schools of Medicine and Engineering.

    “These projects give UAB the opportunity to partner with a new medical school in South Africa for truly innovative research that could have a transformative impact on the lives of women and children in developing areas,” said Selwyn M. Vickers, M.D., senior vice president for Medicine and dean of the School of Medicine. “The fact that we received two of the three project awards shows our competitiveness in patient-centered research and highlights our successful efforts to increase UAB’s impact on global health care delivery.”

    Pillay thinks that the product development experience could produce long-lasting benefits for the Birmingham economy, as well as for patient care in the United States.

    “While we’re developing the cervical pessary, we’re also hoping to spin off other products, like for example, a sensor-based device to monitor cervical dilation of women in labor, so women don’t need to be digitally examined every hour,” he said. “A big part of the future of health care is going to involve sensor-based technology, so I think this project will provide invaluable lessons and expertise for local scientists and researchers. This project is going to help us build capacity locally.”

  • Landefeld named to U.S. Preventive Services Task Force
    UAB’s Landefeld named to government panel that helps determine recommendations on preventive health measures.

    C. Seth Landefeld, M.D., professor and chair of the Department of Medicine at the University of Alabama at Birmingham, has been appointed to theU.S. Preventive Services Task Force. The task force is an independent, volunteer panel composed of experts from many health-related fields, including internal medicine, pediatrics, behavioral health, obstetrics/gynecology, and nursing. Each is appointed by the director of the Agency for Healthcare Research and Quality, a part of the U.S. Department of Health and Human Services.

    Each year, the task force examines the evidence base for preventive health services — such as screenings, counseling services and preventive medications — and delivers an annual report to Congress with recommendations about whether specific clinical preventive practices help or harm the health of Americans. While its recommendations have sometimes been controversial, specifically related to mammograms for women under 50 and prostate cancer screening, the task force has had a positive impact on the role of prevention in routine doctor visits over the past 20 years.

    “We are proud to congratulate Seth on this prestigious new appointment,” said Selwyn M. Vickers, M.D., senior vice president for Medicine and dean of the UAB School of Medicine. “We are confident that his experience, skill and leadership will serve the task force well.”

    Landefeld is internationally known for his work in geriatrics, general internal medicine and health care research, with the emphasis of his work aiming to personalize health care for the elderly and to improve their outcomes. He is a thought leader on the safe delivery of medicines and care delivery models that improve geriatric outcomes.

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