UAB Center for Clinical and Translational Science 1st Annual Scientific Symposium
The CCTS 1st Annual Scientific Symposium began with Katherine Klinger, PhD, Senior Vice President & Presidential Fellow in Genetics and Genomics at Genzyme Corporation, who presented Translational Medicine: How do we Walk the Walk? Dr. Klinger emphasized the importance of accelerating the pace of moving fundamental discoveries into practical applications that enhance health. The typical length of time to move a small molecule drug or protein from bench to beside is 10-15 years – very costly and very risky. Even though it takes so long to go through the process, there is a less than 5% success rate that small molecule drugs and proteins will actually be approved. Most compounds fail due to lack of efficacy (46%); other reasons for failure include animal or human toxicity, adverse events, or pharmacokinetics. Dr. Klinger proposed an opportunity to improve the odds by optimizing disease models and developing valid markers to accelerate trials in man.
Two speakers were funded in the inaugural round of the Translational Research Intramural Grant Program (CCTS Pilot Program) in 2008 and presented their work.
Hyunki Kim, PhD presented his research on Physiologic MRI for Early Therapy Assessment in Pancreatic Adenocarcinoma. Diffusion-weighted imaging (DWI) or dynamic-contrast enhancement MR imaging (DCE-MRI) were used to measure early physiologic changes in orthotopic pancreatic tumor xenografts following chemotherapies and/or targeted therapies in SCID mice. DWI was used to evaluate a novel anti-DR5 antibody TRA-8 with and without gemcitabine. DCE-MRI was used to evaluate an anti-EGFR antibody cetuximab with and without irinotecan. Both studies showed a decrease in tumor size with the most dramatic changes in the antibody and drug combinations.
Raegan Durant, MD presented PUSSH: The Pilot for Understanding Social Support and Hospital Use for Heart Failure. Dr. Durant compared the psychometric properties of three existing social support scales to examine their reliability and validity in a population of heart failure patients. The three scales were the Medical Outcomes Study Social Support Survey (MOS-SSS), the Personal Resource Questionnaire 85 (PRQ-85), and the Multidimensional Survey of Perceived Social Support (MSPSS). Surveys were given in person at the hospital and 2 weeks later by telephone. MOS-SSS had the highest internal validity and test-retest reliability, was informative regarding emotional and tangible support, and assessed distinct aspects of social support. Future plans include studies to examine relationships among social support, self-management and heart failure outcomes.
Two speakers funded by the Alabama Drug Discovery Alliance (ADDA) and the CCTS Drug Discovery Component also presented their work.
Andrew West, PhD presented his project Discovery of LRRK2 Kinase Inhibitors. His research focuses on mutations in LRRK2, which are the most common known cause of Parkinson’s Disease and account for 1-5% of cases in many Western populations and up to 35% in certain ethnicities. Through in vitro assays, it has been demonstrated that mutations increase LRRK2 kinase activity, which is required to block neurotoxicity. Factors that mitigate kinase activity may represent novel therapeutics to block neurodegeneration in Parkinson’s. More research is being done on a three part screening for identification of small molecule inhibitors of LRRK2 with therapeutic potential.
Krister Wennerberg, PhD presented his research on Discovery and Development of Ect2 Inhibitors as Anti-cancer Drugs. During the phases in cell division, the molecular events during cytokinesis have not been actively pursued as anti-cancer targets. The Ect2 stands out as a particularly interesting anti-cancer target due to its essential role in cytokinesis; because it is commonly overexpressed in cancers such as gliomas, ovarian, and lung cancers; and because the overexpression is correlated with metastatic behavior and poor clinical outcome. The next steps will include high throughput screening and follow-up assays to identify specific inhibitors that will establish whether small molecule inhibitors of Ect2 can act as potent anti-cancer agents.
An afternoon poster session followed with thirteen posters. Presenters and their research included the following:
- Jessica Alvarez, MS, RD – Dietary Vitamin D and Calcium Are Differentially Associated with Insulin Sensitivity among African American and European American Premenopausal Women
- Elizabeth Brown, PhD, MPH – Molecular and Genetic Epidemiology (iMAGE) Study of Myeloma
- Nikki Bush, MS, RD – Maternal gestational glucose and offspring indices of insulin resistance and secretion
- David D. Chaplin, MD, PhD – Myeloid-Derived Regulatory Cells in the Airways of Patients with Asthma and COPD
- Nefertiti Durant, MD, MPH – Exercise in Young African American Women: Advancing Methods of Promotion of Physical Activity: WEBWALK
- W. Timothy Garvey, MD – Identifying Agonists of NR4A3 Orphan Nuclear Receptor for the Treatment of Insulin Resistance
- Kenneth Hoyt, PhD – On the potential of contrast-enhanced ultrasound for monitoring breast cancer response to antiangiogenic therapy
- Rajesh K. Kana, PhD – Structural integrity of White Matter in Autism: a diffusion tensor imaging (DTI) study
- Michal Mrug, MD – Timing of the development switch regulating cystogenesis in humans
- Lisa M. Schwiebert, PhD – The effect of aerobic exercise on asthma-related responses in adults
- Adrie JC Steyn, PhD – Role of Nitric Oxide and Carbon Monoxide in Active Pulmonary Tuberculosis
- David E. Vance, PhD– Speed of Processing Training in Adults with HIV: A Pilot Study
- Sadanandan E. Velu, PhD – Synthesis and Anti-Breast Cancer Activity of Novel Makaluvamine Analogs
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