Research: From the Bench to the Bedside

 AriaIII-APCF-Plus-Enid

Research Themes

The Comprehensive Arthritis, Musculoskeletal and Autoimmunity Center Faculty are organized into thematic workgroups to support and continue to develop the faculty and the scientific initiatives of the research base.  These integrative themes of the research base include:

  • Immunology, autoimmunity and inflammation
  • Genetics and functional genomics
  • Bone, cartilage and connective tissues
  • Experimental therapeutics and biomarkers
  • Neurobehavioral medicine
  • Epidemiology, outcomes and prevention

Members often work at the interface of several themes, with ‘touch points’ and ‘cross-over points’ being driven by the scientific opportunity characteristic of our collaborative, interactive environment.

 

Research Projects

Despite a challenging NIH funding environment, the Center has successfully sustained a very robust extramural portfolio, both in the number and magnitude of interdisciplinary, multi-investigator grants. The Awards currently managed by the Center are below. In each, the Center has provided support for the scholarly leadership and intellectual environment, for the integration of fundamental and clinical translation and for planning and management.


RDCC

Rheumatic Disease Core Center (John D. Mountz, MD, PhD, Director, NIAMS P30 AR48311)


The goal of the UAB Rheumatic Diseases Core Center is to stimulate collaborative and innovative interdisciplinary research to enhance our fundamental understanding of disease mechanisms and their application to human rheumatic diseases. Through this understanding, the UAB RDCC's goal is to improve the diagnosis and treatment of patients with arthritis and musculoskeletal diseases. The strategy of the UAB RDCC is to draw on the strengths of the UAB research community to provide essential scientific tools and technologies, to enlist new investigators, to foster the sharing of knowledge and to nurture collaborations among translational and basic science investigators in the fight against rheumatic diseases through the creation and support of a vibrant scientific culture of discovery and innovation. Accordingly, our specific aims are:

  1. 1. to facilitate rheumatic disease research through Research Core facilities (listed below), which provide scientifically rigorous, state-of-the-art techniques necessary for improved understanding of disease pathogenesis and the development of new treatments;
    1. Comprehensive Flow Cytometry Core (J. D. Mountz, Director; O. Kutsch, T. Randall, Co-Directors)
    2. Analytic Imaging and Immunoreagent Core (K. T. Keyser, Director; M. A. Accavitti-Loper, C. Weaver, Co-Directors)
    3. Analytical Genomics and Transgenics Core (R. A. Kesterson, Director; J. Edberg, D. Absher, Co-Directors)
  2. to support outstanding Pilot & Feasibility research projects drawing on the unique strengths of the RDCC research base and using innovative tools and approaches in biomedical science; and
  3. to provide career development and career enrichment activities to enhance both the mentorship of talented investigators as independent researchers and the continuing education of all of our investigators.

To achieve its specific aims, the UAB-RDCC has worked continuously with its Research Core facilities to develop technical capacities, to assess user needs and to provide a variety of formats for outreach and enrichment. For example, see the "Fundamental and Practical Applications of Light Microscopy in Biological Sciences" course. The RDCC leadership team has worked with the Institution to support the continued development of available tools and technologies for rheumatic diseases research, and through these efforts, the UAB-RDCC provides the opportunity for our investigators to commit their programs to the mission of NIAMS.

 

MCRC

UAB Multidisciplinary Clinical Research Center (S. Louis Bridges, Jr., MD, PhD, Director; NIAMS P60 AR064172)

 

The UAB Multidisciplinary Clinical Research Center (MCRC) is a program uniquely positioned to promote research related to the causes, diagnoses, treatments and improved care of patients with arthritis and musculoskeletal diseases. The MCRC builds on capabilities of the CAMAC and its thematic workgroups, and is centered on an outstanding Methodology Core (Redden, Core Director) comprised of experts in biostatistics, data management, statistical genetics and bioinformatics, and outcomes/health services research, all with a proven record of collaborative clinical investigation in musculoskeletal diseases. Currently, the Center supports two innovative projects:
  1. Facilitating Treat-to-Target Using Novel Health Technology with Decision Support (Curtis, Project PI);
  2. Adaptive Immune Responses to Gut Microbiota in Juvenile & Adult Spondyloarthritis (Elson, Project PI);
 
The established mission of the MCRC Methodology Core is to develop and provide state of the art methodology and methodological education in the collaborative support of clinical and translational research in arthritis and musculoskeletal disease (MSD) at the local, regional, national, and international level. Toward this goal, the Core will continue to provide the statistical, epidemiological, outcomes research, statistical genetics, economics/cost effectiveness and bioinformatics leadership and expertise required to develop and perform cutting edge clinical research in arthritis and MSD it pursues four broad goals to:
  1. Support the design, data collection, management and analytic efforts of the MCRC projects
  2. Nurture original research in methodology applicable to clinical research in arthritis and MSD
  3. Develop new investigators in the area of arthritis and MSD research
  4. Provide methodology seminars, workshops and mini-courses to introduce the newest methodological approaches to the MCRC research base.

    CoRT



    UAB Center of Research Translation (CoRT)
    (Kenneth G. Saag, MD, MSc, Director; S. Louis Bridges, Jr, MD, PhD, Co-Director; P50 AR060772)

    Gout affects roughly 1-2% of the U.S. population. With the “Graying of America”, the societal burden of gout will likely grow. While the causes of hyperuricemia are known, and efficacious treatments for gout are available, there are large gaps in the quality of care of gout patients. It is well known is that gout, hyperuricemia, and vascular disease are more common among African Americans than Caucasians, yet little is known about the impact environmental factors have in increasing risk of gout in this minority population. To address these gaps our multi-disciplinary UAB CORT is conducting 3 research projects focused around the theme of "Gout and Hyperuricemia: from Bench to Bedside to Backyard”.
    The objective of the UAB CoRT is to conduct outstanding, innovative research projects. Our projects use state of the art tools from translational research areas of epidemiology, biostatistics, and outcomes. Our current projects include:
    1. The Effects of Urate Lowering Therapy on Inflammation, Endothelial function, and Blood Pressure (Saag, KG; Calhoun, D, MPI)
    2. Determinants of Achieving Target Serum Urate in Gout and Safety of Gout Treatments (Singh, J, PI)
    3. A Novel Centralized 'Virtual' Gout Clinic for Chronic Gout Management (Curtis, J.R., PI)
    Administratively, the UAB CoRT aims to foster the development of pilot and feasibility projects and the development and application of new translational methods of research in gout and hyperuricemia; as well as promote the training of clinical investigators in methods of research applicable to gout and hyperuricemia.
    Finally, and most importantly, the mission of our center is to improve the health of patients with gout and hyperuricemia. By applying scientifically rigorous, state-of-the-art methodology to clinically important questions in translational investigation and educating clinical investigators in ways to predict, treat, or prevent gout and hyperuricemia, we hope to do just that.

     

    Clinical Trials

    The University of Alabama at Birmingham is committed to providing the highest quality medical care to its patients. To accomplish this goal, it is sometimes necessary to conduct research studies to try to improve existing medical treatments. This might involve the testing of new drugs or procedures. The Comprehensive Arthritis, Musculoskeletal and Autoimmunity Center provides the opportunity to participate in a variety of clinical trials that impact arthritis, musculoskeletal, immunologic and autoimmune diseases.

     

    ACIP

    The Arthritis Clinical Intervention Program (ACIP)  is continuously evaluating new therapies for rheumatic diseases including clinical trial therapies for people who have less than optimal responses to conventional therapy. It has conducted over 300 rheumatology trials (Phase I-IV) that have provided significant information to the improvement and advancement within the field of Rheumatology and Immunology. All our doctors are Board Certified Rheumatologists with many years of research experience.

    For more information about ACIP click here.

    Mucosal Immunology Clinical Trials

    Mucosal Immunology Clinical Trials. The UAB Division of Gastroenterology and Hepatology, ranked nationally and internationally as a leading center for digestive and liver disorders, has participated in over 60 clinical trials in the past 5 years. These trials offer the latest in drug therapy and other novel approaches to digestive disorders including inflammatory bowel disease (Crohn’s disease, ulcerative colitis) and viral hepatitis.

    For more information click here.

    Osteoporosis Clinical Trials

    The UAB Osteoporosis Prevention and Treatment Clinic provides complete, expert care, from clinical and therapeutic services to helpful education and information programs. Specialists in the fields of osteoporosis, nutrition, and physical therapy work collectively to help patients treat existing conditions and prevent further complications with proper medication, diet, and exercise.

    For more information, click here.

     

    UAB Programs and Centers with which CAMAC Members are Affiliated


    Genetics of SLE

    Program Project in the Genetics of SLE (Robert P. Kimberly, MD, Director, NIAMS, P01 AR049084)

     

    The goal of the Program Project in the Genetics of SLE is to identify the genes responsible for susceptibility to and severity of SLE in ethnic minorities. The investigative team is exploring candidate genes, the role of copy number variation and the genetic contribution to disease severity and outcome over time. This is achieved by continuing to build the longitudinal collaborative cohort (PROFILE) and assessing the impact of genotype on the phenotype of clinical outcomes in SLE. To implement the scientific strategy, the Program supports four innovative projects. Each of these Projects is coordinated through an Administrative Core and a rigorous Genetic Epidemiology and Biostatistics Core which serves each project. Working together, the investigators of this P01 anticipate making major advances in our understanding of the genetic variants underlying SLE in ethnic minorities.

    For more information, click here

    Innate and Adaptive Immunity in IBD



    Program Project in Innate and Adaptive Immunity in Inflammatory Bowel Disease (Charles O. Elson, III, MD, Casey Weaver, MD, Co-PIs; P01 DK071176)

     

    The inflammatory bowel diseases (IBD) involve complex abnormalities in the innate and adaptive immune response to the Intestinal microbiota. Data from experimental models has found that CD4 T cells are the effector cells mediating disease in most instances, that the enteric bacterial flora drives this pathologic response, and that the innate immune system (epithelium, dendritic cells, macrophages) is a critical link between these two elements. Thus, the major focus of this Program Project is on the interaction of the innate and adaptive immune responses with the microbiota and its products and on the genes that affect these interactions. The Program Project is directed by Dr. Charles Elson and consists of four Projects and two Cores.

     

    • Project 1, headed by Dr. Elson, uses flagellins as probes of the normal T cell homeostatic response in the intestine. Studies address the hypothesis that CD4 T cell effector subsets in the intestine maintain homeostasis by a number of different pathways that can compensate for one another, that these pathways have limits beyond which intestinal inflammation results, and that homeostasis can be restored by augmentation of regulatory T cells.
    • Project 2, headed by Dr. Robin Lorenz, uses the mdr1a knockout model to address the hypothesis that the absence of the mdr1a encoded membrane pump leads to dysfunctional handling of xenobiotics, which results in abnormal development and function in cell types that express the aryl hydrocarbon receptor resulting in spontaneous.
    • Project 3, headed by Dr. Casey Weaver who continues his studies on Th17 cells in the intestine and their role in IBD. He uses novel cytokine reporter and other mutant mouse lines to test the hypothesis that Th17 and "Th1-like" cells cooperate to sustain intestinal inflammation to intestinal microbiota antigens in IBD, that both cell types emerge from a common early Th17 developmental pathway, and that IL-23-dependent memory Th17 cells are required for sustained IBD pathogenesis.
    • Project 4 is led by Dr. Stephan Targan at Cedars-Sinai Medical Center in Los Angeles, CA. This Project utilizes a large panel of patient materials to define the Innate and adaptive Immune response in patients with Crohn's disease who have seroreactivity to CBir1 flagellins to test the hypothesis that immune response to CBIr1 flagellin defines a population of patients with genetic variations of the IL-23, IL-17, and IL-22 pathways, as well as variations in TL1A gene expression, resulting In a severe disease course in IBD.

    The Animal Model Core will centralize the production of mice with experimental colitis, provide for a central pathologic analysis, and generate stocks of genetically-modified stocks of mice for use in the Projects. The long-term goal is to increase our understanding of the fundamental mechanisms of IBD in order to develop better diagnostic and therapeutic strategies for patients.

     

    Program in Immunology

    Program in Immunology (Harry Schroeder, MD, PhD, David D. Chaplin, MD, PhD, Co-Directors

    This multidisciplinary program consists of over 100 UAB Faculty who identify themselves as basic or clinical immunologists representing 5 Schools, 22 Departments and 15 Divisions at UAB. With over $45M in FY 2008 from the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Arthritis, Musculoskeletal, and Skin Diseases (NIAMS), the two NIH funding agencies most focused on host defense, immunology, and inflammation research, this represented about 25% of the entire NIH research portfolio at UAB.

    To learn more about the UAB Program in Immunology, click here.

     

    Digestive Health Center

    UAB Digestive Health Center (Mel Wilcox, MD, John Christein, MD, Co-Directors)

    The UAB Digestive Health Center’s top priority is helping patients diagnosed with ulcerative colitis or Crohns disease to manage their lifestyle and digestive disease effectively. It is a one stop shop bringing together gastroenterologists and surgeons in one clinical practice, streamlining coordination of care between the two connected disciplines and simplifying access to numerous clinical subspecialties, including nutrition and pain management, that are key to lifestyle management and improving disease treatment or control. The Center features specialists in gastroenterology and hepatology, colorectal surgery, hepato-pancreateo-biliary and transplant surgery, and nutrition working together to form a multidisciplinary team of digestive health experts.

    Digestive Health Center Strengths:

    • Single, convenient location for patients to see their doctors
    • Advanced gastrointestinal evaluation and testing
    • State-of-the-art diagnostic and functional imaging
    • Innovative minimally-invasive techniques to treat all types of gastrointestinal diseases

    To learn more, click here.

    dsmCERTs

    UAB Deep South Arthritis and Musculoskeletal Center for Education and Research on Therapeutics (CERTs) (Kenneth G. Saag, MD, MSc, Director; AHRQ U19 HS021110)

    Musculoskeletal disorders (MSD) impose a growing societal burden. Although many new therapeutic options are available, questions on effectiveness, efficiency, and equity of care remain unanswered. MSDs exert an especially heavy toll on the elderly and other disadvantaged and underserved subpopulations, including racial/ethnic minorities, children, & persons with co-morbidities.

    The UAB Deep South Arthritis and Musculoskeletal CERTs seeks to:

    • Improve safety and effectiveness of MSD therapeutics through 4 projects that build on our past work and address the programmatic areas of comparative effectiveness research (CER), tool development, health systems interventions and translating research into practiceby
      • Comparative Effectiveness of NSAIDs vs. Narcotics after Joint Replacement Surgery (Singh, Project PI)
      • A Novel Tool and Multi-Modal Intervention for Improving Osteoporosis Treatment Adherence (Muntner, Project PI)
      • Informed Consent Tools for Pragmatic Clinical Trials in Musculoskeletal Diseases (Saag, Project PI)
      • Assessing Comparative Effectiveness of Biologics and Communicating Risk in Juvenile and Adult Inflammatory Arthritis (Beukelman, Curtis, Project MPIs)
    • Educate health care practitioners, patients, caregivers, pavers, and policy makers while implementing and disseminating our research and educational portfolio
    • Develop concept briefs and other nascent research and education ideas into full scale projects and products for dissemination in cooperation with AHRQ, the CERTS Scientific Forum, and our large network of partners.
    For more information click here.

    CCTS

    Center for Clinical and Translational Science (Robert P. Kimberly, MD, Director, NCATS UL1 TR000165)

    The UAB CCTS will enhance human health by driving scientific discovery and dialogue across the bench, bedside, and community continuum. The CCTS Components support this overall mission in a highly integrative network of relationships. Success in creating such an environment is dependent upon success in achieving five strategic priorities:

    • Enhancing research infrastructure
    • Promoting investigator education, training and development
    • Accelerating discovery across the T1 interface
    • Expanding value-added partnerships
    • Building sustainability

     For more information about the CCTS, click here.

    COERE

    Center for Outcomes and Effectiveness Research and Education (COERE) (Kenneth Saag, MD, MSc, Director)

    The COERE offers integrated scientific expertise and experience in all areas of outcomes and effectiveness research, including: quantitative methods in health services research; quality measurement and improvement; patient-based outcomes measurement; epidemiologic and population-based research; comparative effectiveness research; pharmaco-epidemiology; economic and decision analytic modeling; clinical data analysis and analysis of large administrative datasets; and health informatics. Center leadership applies this expertise to outcomes and health services research through an active program of collaborative, investigator-initiated research and cooperative agreements.

    For more information about COERE, click here

    Immunology Training Program

    Training Grant in Immunologic Diseases and Basic Immunology (Harry W. Schroeder, Jr., MD, PhD, Director, Laurie Harrington, PhD, Associate Director; NIAID T32 AI007051)

    The multidisciplinary UAB Immunology Training Program is focused on training highly motivated pre-doctoral students, and PhD and MD graduates in the fields of translational and fundamental immunology. The primary focus of UAB’s immunology research remains the elucidation of pathogenic mechanisms operative in diseases of immune etiology.

     

    Click here for more information.

     

    HSOER Training Program

    UAB Health Services, Outcomes, and Effectiveness Research Training Program (Kenneth G. Saag, MD, MSc, Director; AHRQ T32 HS013852)

    The UAB HSOER Training Program is a collaborative effort of the UAB Center for Outcomes and Effectiveness Research and Education and the UAB Lister Hill Center for Health Policy. This T32 provides predoctoral and postdoctoral trainees with high quality training, individual and team mentoring, and an intensive didactic curriculum and multi-disciplinary training experience, promoting the methodological skills and other core competencies required for success as independent HSOER investigators. Contact Information: Ryan Outman Tel: (205) 996-9672 This email address is being protected from spambots. You need JavaScript enabled to view it.