Day 1 :
Johns Hopkins University USA
Time : 09:00-09:30
Mingzhao Xing, MD, PhD, is Professor of Medicine, Oncology and Pathology, Co-Director of the Thyroid Tumor Center, and Chief of the Laboratory for Cellular and Molecular Thyroid Research at the Johns Hopkins University School of Medicine. He subsequently completed his medical residency at the Greater Baltimore Medical Center and clinical fellowship in endocrinology and metabolism at the Johns Hopkins Hospital before joining the Johns Hopkins endocrine faculty. Dually certified in Internal Medicine and Endocrinology, he practices clinical endocrinology as a subspecialty consultant and teaching attending at the Johns Hopkins Hospital while leading a research laboratory there focused on thyroid studies as a physician scientist. Supported by the American Cancer Society and NIH R0-1 grants, his laboratory has been studying molecular, genetic, and epigenetic mechanisms of thyroid cancer and their clinical translation. He has published extensively in prestigious journals including Journal of Clinical Endocrinology and Metabolism, Cancer Research, Clinical Cancer Research, Journal of Biological Chemistry, Journal of Clinical Investigation, JNCI, Journal of Clinical Oncology, JAMA, The Lancet, and Nature Reviews Cancer. He is co-holder of the USA patent on the initial discovery and clinical characterization of the BRAF V600E mutation in thyroid cancer. He received various awards, such as the Maryland Innovator Award, American Cancer Society’s RSG Award and many more.
Thyroid cancer is a common endocrine malignancy with a rapidly rising incidence in many countries in recent years. Most cases of thyroid cancer have a good prognosis, but some seem to be bound to poor outcomes with increased disease recurrence, treatment refractoriness, and mortality. Conventional approach to risk stratification of thyroid cancer is solely based on clinic pathological criteria, which has proven to be often ineffective. An area that is revolutionizing the risk stratification and hence management of thyroid cancer is the clinical translational research on prognostic molecular markers in thyroid cancer, as best exemplified by BRAFV600E mutation. Numerous studies have demonstrated a strong association of BRAF V600E mutation with poor clinic pathological characteristics of PTC, such as lymph node metastasis, extra thyroidal invasion, advanced tumor stages, tumor recurrence, and patient mortality, establishing a remarkable prognostic value of this molecular marker. BRAF mutation can be detected on thyroid fine needle aspiration biopsy specimens, so this prognostic marker can be used even preoperatively to assist risk stratification and surgical and medical managements at an early stage of the treatment of thyroid cancer. The use of the recently discovered TERT promoter mutations in combination with BRAF mutation makes even more effective this molecular marker-based risk stratification and hence tailored management of thyroid cancer. Our group has played a leading role in the last 10 years in the discovery and characterization of these prominent molecular markers in thyroid cancer. This presentation will provide a comprehensive discussion on this exciting clinical translational research area of thyroid cancer medicine.
King Saud University Saudi Arabia
Keynote: Gut-brain axis-based biomarkers as predictive tools in testing efficacy of carnosine and carnitine in rodent model of autism
Time : 09:30-10:00
Afaf El-Ansary has completed her PhD at the age of 37 years from Ain Shams University-Egypt and Postdoctoral studies from National Research Centre. She is a Professor in Biochemistry Department, Science College, King Saud University. She has published more than 85 papers in high impact factor journals and serving as a reviewer and as an Editorial Board Member of repute journals.
Exposures to environmental toxins are now thought to contribute to the development of autism spectrum disorder. Progress in understanding and treating autism will require translational research efforts to transfer knowledge through successive fields of research from basic scientific discovery to public health impact. A developmentally abnormal gut microbiota may in turn affect both the gut-brain axis and brain development and contribute to the etiology of autism. Propionic acid (PA) found as a metabolic product of gut bacteria has been reported to mimic/mediate the neurotoxic effects of autism. Results from animal studies may guide investigations on human populations toward identifying environmental contaminants that produce or drugs that protect from neurotoxicity. In a three successive independent experimental design, we tested the neurotoxic effect of PA either orally administered or biologically induced in clindamycin-treated rat pups. The oral administration was used to confirm the role of gut-brain axis in the induction of autistic features probably found in treated rats. Additionally, Clindamycin was used to ascertain the role of overgrowth of Clostridia species as PA producer in inducing autistic features in animals. In both groups, a panel of biomarkers were measured compared to healthy untreated rat pups. These biomarkers were selected to represent DNA damage, oxidative stress, and neurochemistry, and neuroinflammation related signaling. The selection of these markers was based on our clinical data obtained from patients with autism which recorded highspecificity and sensitivity when analyzed usingReceiver Operating Characteristics (ROC) and excellent predictive values using predictiveness curves. Our work was extended to test the therapeutic efficacy of carnosine, and carnitine. The obtained data confirm the role of propionic acid in inducing persistent autistic features in rat pups with oral administration being more neurotoxic than theinduction of propionic acid bacterial producers. Additionally, both supplements were effective in ameliorating the toxic effects of PA. In conclusion, although our investigations show evidences of the efficacy of the tested supplementsin ameliorating most of the impaired biomarkers in PA- rodent model of autism, still there is need for better designed and registered trials for at least six months in order reliably to identify a confirmed proper effect.
Yeungnam University Republic of Korea
Time : 10:00-10:30
Kyung-Hyun Cho obtained his PhD from the Kyungpook National University of South Korea in 1998 and gained his Postdoctoral training at the University of Illinois at Urbana-Champaign until 2000. He joined Cleveland Clinic Foundation as a Research Doctor until 2001. Back home, he worked at Korea Research Institute of Bioscience and Biotechnology as senior scientist for 4 years. Then he moved to the Yeungnam University (YU), in 2005, where he is currently the Full Professor (tenured) and Head of the Research Institute of Protein Sensor (RIPS) and BK21 plus Serum Biomedical Research and Education Team in the YU. He published more than 70 papers in well known journals and filed more than 20 patents.
It has been reported that glycation could also occur in high-density lipoproteins (HDL) in blood. High-density lipoproteincholesterol (HDL-C) is inversely associated with incidence of cardiovascular disease and is directly related to longevity. In type 2 diabetes patients, blood infusion of rHDL caused reduction of plasma glucose levels by increasing plasma insulin in pancreatic beta cells, which raised the feasibility of a wider clinical application of rHDL from cardiovascular disease to diabetes. The glycation resulted in severe loss of beneficial functions of HDL regarding anti-senescence and anti-diabetic, and anti-atherosclerosis activity due to functional and structural modification with increased protein degradation. To compare the change in lipoprotein metabolism with aging, we analyzed the lipid and protein compositions of individual lipoprotein fractions. Healthy and non-obese elderly subjects (elderly group, n=26) had a serum lipid profile within the normal range, although slightly higher than in young subjects (control group, n=18). However, the elderly group had a 2-fold higher serum uric acid level and triglyceride (TG)/high-density lipoprotein (HDL)-cholesterol ratio. The elderly group had less antioxidant ability and elevated TG content in HDL with enhanced cholesteryl ester transfer activity. An elevated level of advanced glycated end products in lipoproteins and fragmentation of apoA-I were present in the elderly group, with detected lower apoA-I level and more multimerizedapoA-I in HDL. The protein levels of apoA-I, apoC-III, and serum amyloid A in lipoprotein-deficient serum were increased in the elderly group.
I M Sechenov First Moscow State Medical University Russia
Keynote: Antibodies with functionality as a new generation of translational tools to monitor, to predict and to prevent demyelination
Time : 10:30-11:00
Sergey Suchkov was born in 11.01.1957, a researcher-immunologist, a clinician, graduated from Astrakhan State Medical University, Russia, in 1980. He has been trained at the Institute for Medical Enzymology, The USSR Academy of Medical Sciences,National Center for Immunology (Russia), NIH, Bethesda, USA) and British Society for Immunology to cover 4 British university facilities. Since 2005, he has been working as Faculty Professor of I.M. Sechenov First Moscow State Medical University and Of A.I.Evdokimov Moscow State Medical & Dental University. From 2007, he is the First Vice-President and Dean of the School of PPPM Politics and Management of the University of World Politics and Law.In 1991-1995, He was a Scientific Secretary-in-Chief of the Editorial Board of the International Journal “Biomedical Science” (Russian Academy of Sciences and Royal Society of Chemistry, UK) and The International Publishing Bureau at the Presidium of the Russian Academy of Sciences. In 1995-2005, he was a Director of the Russian-American Program in Immunology of the Eye Diseases. He is a member of EPMA (European Association of Predictive, Preventive and Personalized Medicine, Brussels-Bonn), a member of the NY Academy of Sciences, a member of the Editorial Boards for Open Journal of Immunology and others. He is known as an author of the Concept of post-infectious clinical and immunological syndrome, co-author of a concept of abzymes and their impact into the pathogenesis of auto immunity conditions, and as one of the pioneers in promoting the Concept of PPPM into a practical branch of health services
Biomarkers enable early diagnosis, guide targeted therapy and monitor the activity and therapeutic responses across the diseases. So, identification and validation of biomarkers of newer generationsto create a new strategy based upon subclinical recognition of the latter long before the disease clinically manifests itself is of great value. Among the best-validated predictive biomarkers are autoimmunity-related ones (including antibodies/Abs). Meanwhile, multiple sclerosis (MS)whilst beinga chronic autoimmune disorder would result in a destruction of myelin by different factors, including autoAbs. Along with canonical Abs, we have discovered a new family of Abs proven to be endowed with myelin basic protein (MBP)-targeted proteolytic activity (Ab-proteases). The proteolytic property mentioned is considered to serve a functional property of the biomolecule. Most (72-78%) of anti-MBP autoAbsharvested from MS patients and mice with EAE exhibited MBP-specific proteolytic cleavage of MBP.The activity of Ab-proteases markedly differed: (i)betweenMS patients and healthy controls and (ii) inpatients with different types of MS course. Moreover, the activity demonstrated a significant correlation with demyelination, neurological deficiency and thus with the disability of the patients. Of greater value isa sequencespecificity of Ab-proteasesto attack targeted sequences located in dominant fivesites of MBP. Most of those sites whilst being immuno dominant are concentrated within 43-170 of MBP.Two sites from the set would comprise 81-103and 82-98, which, in turn,whilst being sequence-specific, highly immunogeneic and encephalitogeneic both, proved to be major inducers of very aggressive EAE in SJL mice.In humans, both 81-103 and 82-98 have been proven to be major MBP targets to be attacked by Ab-proteases obtained from patients with secondary-progradient courses of MS, progression phase (SPPP), and with remittent course of MS, exacerbation phase (REP), both are with aggressive inflammation. Two extra sites from the same 43-170set are located within 43-68 and 146-170 that proved to be inducers of moderate EAE and thus targets to be attacked by Ab-proteases in MS patients with secondary-progradient courses, stabilization phase (SPSP), and with remittent course, remission phase (RRP), both are with inflammation quenched. So, the most immunogeneic and encephalitogeneic epitopes responsible for generating aggressive bursts are concentrated in three specific areas of MBP: (i) the strongest one is in the smallest 82-98; (ii) a weaker epitope is formed by a longer 81-103 subsequence; and (iii) an epitope with the lowest immunogeneic and encephalitogeneic properties is rooted in a rather long 143-170 sequence defined. The relatives being seropositive for Ab-proteases were being monitored for 3 years whilst demonstrating stable growth of the Ab-associated proteolytic activity when were being under the study.And when the activity reached its mid-level, we identified primary clinical and MRI manifestations to be coincided with the Ab-associated proteolytic activity. And then the proteolytic activity was being further escalated due to the time of progression, type of the disorder, and disability of the patient.Meanwhile, a substantial proportion (around 34%) of relatives demonstrating low-active Ab-proteases with no trends to grow had hadsubclinical evidence of autoimmunity without developing clinically overt dis-ease. The activity of Ab-proteases was first registered at the pre-early (subclinical) stages of the disorder, whenAb-proteases were still low-active whilst attacking presumably low-immunogeneicsequences, the inflammation is moderate, and the manifestations are thus scarcely visible.As the disorder progresses to transform from subclinical into clinical stages, the activity of Ab-proteases is being escalated to reach the indices to be typical for the clinical stage. And, when bursts of the proteolytic activity were evident, the pre-early stages of REP stage could be predicted, even at no seeing any clinical manifestations.And along with the evolution of the sequence specificity, when we saw an extensive growth of the activity, we could predict transformations in the clinical course, i.e., changing of RRP (moderate one) into SPP (severe one) prior to changing of the clinical manifestations. A spread from one type of epitope to the other one could also be a combinatorial biomarker event to serveas a biopredictor of the interstage transformations and serve prognostically as a dynamic biomarker for monitoring MS patients and persons atrisk at both subclinical and clinicalstages to use specific Ab-proteases (Abs with functionality) defined. In fact, a spread from one sequence to another one could also be used prognostically in the development of chronic autoimmune inflammation and thus neurodegeneration (demyelination and axon loss). So, the activity of Ab-proteases in combination with their sequencespecificity to attack well-defined sets of epitopes to be released from MBP during Epitope Spreading, would confirm a practical value of Ab-proteases to monitor both clinical and subclinical courses of chronic autoimmune inflammation. The primary translational potential of this knowledge is in the rational design of novel diagnostic and therapeutic too to exploit the role of those tools in influencing disease. Ab-proteases can be programmed and re-programmed to suit the needs of the body metabolism or could be designed for the development of principally new catalysts with no natural counterparts. By changing sequence specificity of the Ab-mediated proteolysis one may reach reduction of a density of negative shots made by Ab-proteases against MBP as a target and thus could minimize the overall negative effect on the myelin sheath and, finally, minimizing scales of demyelination. So, further translational studies ofAb-mediated MBP proteolysis may provide a newer generation of posttranslational tools and thus a supplementary biomarker and a targeted tool for assessing the disease progression and predicting disability of the patients.