Day 2 :
The Pharmaceutical research Institute,ACPHS,Albany, USA
Dr. Mousa finished PhD from Ohio State University, College of Medicine, Columbus, OH and Post-doctoral Fellowship, University of Kentucky, Lexington KY. He also received his MBA from Widener University, Chester, PA. Dr. Mousa is currently an endowed tenure Professor and Executive Vice President and Chairman of the Pharmaceutical Research Institute and Vice Provost for Research at ACPHS. Prior to his academic career, Dr. Mousa was a senior Scientist and fellow at The DuPont Pharmaceutical Company for 17 years where he contributed to the discovery and development of several FDA approved and globally marketed diagnostics and Therapeutics. He holds over 350 US and International Patents discovering novel anti-angiogenesis strategies, antithrombotics, anti-integrins, anti-cancer, and non-invasive diagnostic imaging approaches employing various Nanotechnology platforms. His has published more than 1,000 journal articles, book chapters, published patents, and books as editor and author. He is a member of several NIH study sections, and the editorial board of several high impact Journals. His research has focused on diagnostics and therapeutics of angiogenesis-related disorders, thrombosis, vascular and cardiovascular diseases.
Targeted delivery of drug incorporated nanoparticles, through conjugation of tumor-specific cell surface markers, such as tumor-specific antibodies or ligands can not only enhance the efficacy of the anticancer drug but also reduce the unwanted toxicity of the drug. Additionally, multifunctional characteristics of the nano-carrier system would allow for simultaneous imaging of tumor mass, targeted drug delivery and monitoring. A summary of recent progress in nanotechnology as it relates specifically to nanoparticles and anticancer drug delivery will be reviewed. Nano Nutraceuticals using combination of various natural products provide a great potential in cancer management. Additionally, various Nanomedicine approaches for the detection and treatment of various types of clots organ specific delivery, vascular targeting, improved PK / PD, and vaccine will be briefly discussed.
Learning Objectives: Highlight the Role of Nanobiotechnology and other enabling technologies in the followings:
- Targeted Drug Delivery
- Improved PK and PD
- Early detection (Imaging)
- Targeted Delivery of Chemotherapy for optimal efficacy and safety
- Nano synthesis and assembly of various platforms for Targeted Delivery
- Nanobiotechnology in shortening the time and risk of Drug Discovery and Development
Department of Physiology, Teikyo University School of Medicine, Tokyo, Japan
Keynote: Myosin head power stroke does not obey predictions based on the swinging lever arm mechanism of muscle contraction
Time : 9:30 AM - 10 :00 AM
Haruo Sugi graduated from post-graduated school in the University of Tokyo with the degree of PhD in 1962, and was appointed to be an Instructor in Physiology, in the University of Tokyo Medical School. From 1965 to 1967, he worked at Columbia University as research associate, and at the National Institutes of Health as a visiting scientist. Sugi was Professor and Chairman in Teikyo University Medical School from 1973 to 2004 when he became Emeritus Professor. He was Chairman of Muscle Commission in the International Union of Physiological Sciences from 1998 to 2008 (IUPS). He organized Symposia on molecular mechanism of muscle contraction six times, each followed by Proceeding published from University of Tokyo Press, Plenum, Kluwer and Springer and regarded as milestones of progress in this area of research work.
Although more than 50 years have passed since the monumental discovery of sliding filament mechanism in muscle contraction, the molecular mechanism of myosin head movement, coupled with ATP hydrolysis, is still a matter for debate and speculation. A most straightforward way to study myosin head movement, producing myofilament sliding, may be to directly record ATP-induced myosin head movement in hydrated, living myosin filaments using the gas environmental chamber (EC) attached to an electron microscope . While the EC has long been used by materials scientists for the in situ observation of chemical reaction of inorganic compounds, we are the only group successfully using the EC to record myosin head movement in living myosin filaments. We position-mark individual myosin heads by attaching gold particles (diameter, 20nm) via three different monoclonal antibodies, attaching to (1) at the distal region of myosin head catalytic domain (CAD), (2) at the myosin head converter domain(COD), and (3) at the myosin head lever arm domain(LD). First, we recoded ATP-induced myosin head movement in the absence of actin filaments, and found that myosin heads moved away from, but not towards, the central bare region of myosin filaments. We also succeeded in recording ATP-induced myosin head power stroke in actin-myosin filament mixture. Since only a limited proportion of myosin heads can be activated by a limited amount of ATP applied, myosin heads only move by stretching adjacent sarcomere structures. As shown in Fig.1, myosin head CAD did not move parallel to the filament axis in the standard ionic strength (B), while it moved parallel to the filament axis (C). These results indicate that myosin head movement does not necessarily obey predictions of the swinging lever arm hypothesis appearing in every textbooks as an established fact.
Professor, Departments of Biochemistry and Molecular Biology and Biomedical Engineering;Mayo Clinic College of Medicine and Science,Florida, USA
Professor of Biochemistry and Molecular Biology, Mayo Clinic School of Medicine and Science, Jacksonville, Florida, has a joint appointment with the Department of Physiology and Biomedical Engineering. He has specific expertise in key research areas including Cancer, Cardiovascular Diseases and Neurodegenerative diseases. As a postdoctoral fellow, later as an Associate Professor at Harvard Medical School, Boston, he carried out angiogenesis and tumor microenvironment related research. After moving to Mayo Clinic as a Professor and also as Leader of both Tumor Microenvironment program and Translational Nanomedicine Programs, he has been supervising additional research areas including targeted drug delivery and novel drug development. He has published more than 198 peer-reviewed manuscripts in different journals including Nature, Nature Medicine, Caner Cell, Cancer Research, Nano Letters and other highly rated journals. He has several patents and has been involving to develop different start-up companies in the area of therapy and diagnosis of the diseases.
Reactive species, specifically nitric oxide (NO) and hydrogen peroxide (H2O2), activate signal transduction pathways during angiogenesis and other biological systems and therefore play important roles in physiological development as well as various pathophysiologies. Herein, we utilize a near-infrared fluorescent single-walled carbon nanotube (SWNT) sensor array to measure the single-molecule efflux of NO and H2O2 from human umbilical vein endothelial cells (HUVEC) and cancer cells in response to angiogenic stimulation or chemotherapeutic drugs. The nanosensor array consists of a SWNT embedded within a collagen matrix that exhibits high selectivity and sensitivity to single molecules of specific reactive species. We observed that the production of H2O2 following VEGF stimulation is elevated outside of HUVEC, but not for stimulation via nanorods, while increased generation is observed in the cytoplasm for both cases, suggesting two distinct signaling pathways. In addition, we are able to detect the spatial resolution of NO in HUVEC cells in response to VEGF. Moreover, by employing transmission electron microscopy, confocal fluorescent microscopy, and UV-vis spectroscopic analysis, we have confirmed the internalization of DNA-SWCNT in HUVECs. Additionally, by using pharmacological inhibitors as well as genetic approaches, we have found that SWCNT is endocytosed through Rac1- GTPase mediated macropinocytosis in normal endothelial cells. Our work reveals a unique mode of entry of SWCNT in cells and might help to properly formulate SWCNT as nanovectors in biological systems. Moreover, the SWNT platform can be employed for early detection and therapeutic intervention of patients from liquid biopsies; this topic will be discussed as well.