Day :
Keynote Forum
Haval Shirwan
University of Louisville, USA
Keynote: Apoptosis as an effective means of inducing tolerance to pancreatic islets for the treatment of type 1 diabetes
Time : 09:25-09:50
Biography:
Haval Shirwan is Dr. Michael and Joan Hamilton Endowed Chair in Autoimmune Disease, Professor of Microbiology and Immunology, Director of Molecular Immunomodulation Program at the Institute for Cellular Therapeutics. He conducted his Graduate studies at the University of California in Santa Barbara, CA, and Postdoctoral studies at California Institute of Technology in Pasadena, CA. He joined the University of Louisville in 1998 after holding academic appointments at various academic institutions in the United States. His research focuses on the modulation of immune system for the treatment of immune-based diseases with particular focus on type 1 diabetes, transplantation, and development of prophylactic and therapeutic vaccines against cancer and infectious diseases. He is an inventor on over a dozen of worldwide patents, widely published, organized and lectured at numerous national/international conferences, served on study sections for various federal and non-profit funding agencies, and is on the Editorial Board of a dozen of scientific journals. He is member of several national and international societies and recipient of various awards.
Abstract:
Type 1 diabetes (T1D) is an autoimmune disease initiated and perpetuated by T cells targeting various autoantigens expressed by insulin producing beta cells, thereby setting off a serious of immunological reactions that result in the destruction of beta cells, insulin deficiency, and hyperglycemia. Insulin treatment as standard of care is often ineffective in preventing recurrent hyperglycemic episodes with subsequent development of micro and macroangiopathic lesions and the development and progression of chronic complications. Pancreatic islet transplantation has proven effective in improving metabolic control/quality of life and preventing severe hypoglycemia in patients with T1D. Immune rejection, however, severely limits broad application of islet transplantation, irrespective of chronic use of immunosuppression and its sequelae. Therefore, novel approaches that control rejection in the absence of chronic immunosuppression will have significant impact on the field of islet transplantation. T-cells are the primary culprit of islet graft rejection. As such, control of T cell responses has the potential to induce tolerance and treatment of T1D. T cells upregulate Fas receptor and become sensitive to Fas/FasL-mediated killing. Therefore, Fas-mediated apoptosis has great potential to serve as an effective means of inducing transplantation tolerance. Using a novel form of FasL protein with improved apoptotic activity, we have demonstrated the utility of this concept for the induction of tolerance to allogeneic as well as xenogeneic pancreatic islets in preclinical rodent experimental models.
Keynote Forum
Paul J. Davis
Albany Medical College, USA
Keynote: Anti-Apoptotic Actions of Thyroid Hormone in Cancer Cells may limit Effectiveness of Chemotherapy
Time : 08:30-08:55
Biography:
Davis is a graduate of Harvard Medical School and had his postgraduate medical training at Albert Einstein College of Medicine and the NIH. His academic positions have included Chair, Department of Medicine, Albany Medical College. He has served as President, American Thyroid Association, as a member of the Board of Directors of the American Board of Internal Medicine and he is Co-Head, Faculty of 1000 – Endocrinology. He serves on multiple Editorial Boards of His scientific interests include molecular mechanisms of actions of nonpeptide hormones, particularly, thyroid hormone. He and his colleagues described the cell surface receptor for thyroid hormone on integrin ï¡vï¢3 that underlies the pro-angiogenic activity of the hormone and the proliferative action of the hormone on cancer cells. He has co-authored more than 200 original research articles and 30 textbook chapters and he has edited three medical textbooks.
Abstract:
Thyroid hormone as L-thyroxine (T4) is anti-apoptotic at physiological concentrations in a number of cancer cell lines. Among the mechanisms of anti-apoptosis activated by T4 are interference with Ser-15 phosphorylation (activation) of p53 and with TNFï¡/Fas-induced apoptosis, as well as decreased cellular abundance of caspases and of BAX. Such actions of T4 may oppose pharmaceutical anti-apoptotic strategies. The anti-apoptotic effects of thyroid hormone largely are initiated at a cell surface thyroid hormone receptor on integrin ï¡vï¢3. The integrin is amply expressed and activated in cancer cells, but not in nonmalignant, nondividing cells. Nanoparticulate tetraiodothyroacetic acid (Nanotetrac) opposes actions of thyroid hormone initiated at ï¡vï¢3 (PJ Davis, Ann Rev Pharmacol Toxicol 51:99-115, 2011). We have studied the effects of Nanotetrac (10-7 M) in vitro on expression of a panel of apoptosis-relevant cancer cell genes in human breast cancer MDA-MB-231 (AB Glinskii et al., Cell Cycle 8:3562-3570, 2009) and human medullary thyroid carcinoma (mTC, CRL-1803) (M Yalcin et al., J Clin Endocrinol Metab 95:1972-1980, 2010) cell lines. CASP2, MCL2L14, DFFA, BAD and Bcl-Xs are pro-apoptotic genes whose expression was stimulated by Nanotetrac; XIAP and MCL1 are anti-apoptotic genes and their transcription in tumor cells was downregulated by Nanotetrac. Nanotetrac blocked the anti-apoptotic action of thyroid hormone in a stilbene-induced model of apoptosis in glioma cells. Thus, thyroid hormone (T4) is an endogenous anti-apoptotic factor that may oppose chemotherapy-induced apoptosis in ï¡vï¢3-expressing cancer cells. These actions of T4 have been blocked in vitro by Nanotetrac and rationalize medical induction of euthyroid hypothyroxinemia. \\r\\n\\r\\n
Keynote Forum
Diana Anderson
University of Bradford, United Kingdom
Keynote: DNA damage in lymphocytes from healthy individuals and respiratory disease patients, treated ex vivo/in vitro with aspirin and ibuprofen nanoparticles compared to their bulk forms
Time : 08:55-09:20
Biography:
Professor Diana Anderson completed her PhD in the Faculty of Medicine, University of Manchester, UK. She currently holds the Established Chair in Biomedical Sciences at the University of Bradford. She has published over 450 papers and eight books. She has served on 10 editorial boards, has supervised 30 PhD students and is Editor- in- Chief of the Book Series “Issues in Toxicology†for the Royal Society of Chemistry. She has hosted and participated in 56 meetings for the WHO on Chemical Safety. She has been a Vice President of the Institute of Biology.
Abstract:
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