Soren P Sheikh, Professor of Clinical Biochemistry, Dept. Head, Odense University Hospital, grew up in Denmark and received his Bachelor's degree from the University of Copenhagen in 1985. After he obtained his Ph.D. degree from the University of Copenhagen 1992, he finished his clinical education, and continued his laboratory work with signal transduction of 7 TM receptors & microRNA at Rigshospitalet, Copenhagen. He spend one year as a research associate at University of Michigan in 1989, and was appointed Professor at the University of Copenhagen in 1995. Next, he joined Professor Henry Bourne in San Francisco at the UCSF from 1996-1999. In the meantime, Sheikh finished his specialist-degree in Clinical Biochemistry, and was appointed Head of Department Clinical Biochemistry & Pharmacology, Odense University Hospital (OUH) in 1992, and began investigations of stem cell differentiation and clinical application in erectile dysfunction and lymphedema. Sheikh was appointed Head of Center for Regenerative Medicine at OUH in 2015. He has received various awards and grants, with the most representative being a 4 mio $ (USD) grant from the Danish Innovation Foundation in 2017.
Cardiac vascular Disease is the leading cause of death in Europe. Although many human organs regenerate completely upon partial damage, the adult is a clear exception from this paradigm. Instead myocardial infarction results in scar formation, and therapies for cardiomyocyte regeneration are warranted. Recently, it was suggested that newborn mammals have full capacity for regeneration of their hearts after apical resection. Using novel methods of myocardial function and scarring including F-18-fluorodeoxyglucose positron emission tomography (FDG-PET), we have intensively tested this interesting hypothesis. We have applied multiple injury models and analyzed mammalian hearts at longer time points after injury based on the observation that zebrafish hearts pass through a phase of fibrosis before complete regeneration. In addition, we investigated the possibility that apical resection either inhibits, delays, or reverses cardiomyocyte centrosome disassembly and binucleation. None of the injured hearts exhibited full regeneration but instead exhibited persistent scarring and reduced wall motion. Taken together, our work showed that suggests that a potential regenerative program in the new newborn mammalian heart is less likely to emerge due to developmental mechanisms that induce terminal differentiation of cardiomyocytes.
William E Funk is an Assistant Professor in the Department of Preventive Medicine at Northwestern University and an Associate Member of the Robert H. Lurie Comprehensive Cancer Center.
Periods of fetal, infant and early childhood development are remarkably vulnerable to environmental hazards and exposures to toxic chemicals during these critical windows of susceptibility have been linked with disease, disabilities and adverse health in childhood and across the entire life span. As a result, identifying new integrative exposure biomarkers associated with early-life development is of paramount importance. In this study we focused on exposures to small reactive chemicals in blood (i.e., electrophiles). Electrophiles are produced through metabolic processes such as oxidative stress and also have exogenous sources from exposure to toxicants in the environment, thus they represent a broad and important component of the human exposome. However, because electrophiles are short lived in the blood they cannot normally be measured in vivo, which has motivated our group to measure adducts (addition products) that are formed with abundant of blood proteins. While targeted adducts have been measured as exposure biomarkers for decades, here we present a novel untargeted biomarker approach (i.e., adductomics) for mapping the childhood adductome to investigate links between the environment and children’s health. Adductomics is particularly well suited for these investigations because: (1) it captures an integration of exposures occurring during critical periods of development, (2) it captures exposures to both exogenous and endogenous chemicals that can act as environmental triggers and provide insights into underlying biological mechanisms, respectively and (3) can be performed using minimally-invasive bio-specimens, such as cord blood and dried blood spot (DBS) samples. Untargeted discovery experiments were first performed using human serum albumin isolated from plasma samples and enriched to characterize the childhood adductome. We then applied a targeted multiplexed assay to quantify adduct panels in DBS samples, as a minimally-invasive strategy to extend the application of adductomics to population-level research.
Gautam Sethi has completed his Postdoctoral training at University of Texas MD Anderson Cancer Center and then joined Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore in 2008 as an Assistant Professor and was promoted to Associate Professor in 2015. He currently serves as an Academic Editor for prestigious PLOS One, Editorial Board Member of Scientific Reports, BMC Cancer, Pharmacological Research, Frontiers in Pharmacology, Frontiers in Oncology, and ad-hoc Reviewer for several other international journals.
Conventional anti-cancer therapeutic strategies involve the use of chemically synthesized drugs and/or administration of high-energy radiation to circumvent tumor growth. However, these strategies are generally poorly tolerated, often resulting in adverse side effect. As such, there is an urgent need to develop novel anti-cancer therapeutic agents that not only overcome the chemo-resistance barricade, but also elicit minimal side effects and is well tolerated amongst patients of diverse demographics. Plant-based natural drugs contributes to primary health care in approximately 80% of the world’s population, with uses dating back to the ancient times as traditional herbal medicine by physicians such as Hippocrates. Our group is currently exploring the role of STATs family of cytoplasmic transcription factors that transmit signals, mediate intracellular signaling usually generated at cell surface receptors and transmitted to the nucleus. There is a strong evidence to suggest that aberrant STAT3 signaling promotes development and progression of human cancers by either inhibiting apoptosis or inducing inflammation, cell proliferation, angiogenesis, invasion and metastasis. Suppression of activation of STAT3 results in the induction of apoptosis in tumor cells and accordingly its inhibition by approaches such as tyrosine kinase inhibitors, antisense oligonucleotides, decoy nucleotides, dominant negative proteins, RNA interference and chemo-preventive agents have been employed to suppress the tumorigenicity. However, the development of novel drugs for the targeting STAT3 that is both safe and efficacious remains an important scientific and clinical challenge. My talk will provide the evidence for critical roles of STAT3 in oncogenesis and discusses the potential for development of novel cancer therapies based on mechanistic understanding of STAT3 signaling.
Bin Zhou has received his MD in 1986 from Nanjing Medical University, China and Fellowship training in Medicine/Cardiology between 1986 and 1991 from the First Affiliated Hospital of Nanjing Medical University. He has then received his PhD in 1998 from the Department of Experimental Medicine and Pathobiology of the University of Toronto, Canada, in the laboratory of Professor Marlene Rabinovitch, where he studied vascular stenosis. In 2002, he was recruited to Vanderbilt University as an Assistant Professor of Pediatrics (Cardiology) to establish his independent research program. He was recruited to Albert Einstein College of Medicine in 2008 as an Associate Professor of Genetics, Pediatrics and Medicine (Cardiology) and promoted to Full Professor in 2013.
Normal aortic valve is composed of valve endothelial cells (VEC) and valve interstitial cells (VIC). VIC is the major cell population and has distinct embryonic origins in the endocardium and cardiac neural crest cells. Cell signaling between VEC and VIC plays critical roles in aortic valve morphogenesis. Disruption of major cell signaling pathways results in aortic valve malformations, including bicuspid aortic valve. Bicuspid aortic valve is a common congenital heart valve disease that may lead to calcific aortic valve disease, but there is currently no effective medical treatment for this beyond surgical replacement. Human studies have identified that NOTCH1 mutations cause bicuspid aortic valve. Here we present our findings from mouse studies demonstrating that NOTCH1-Tnfa signaling is required for development and homeostasis of aortic valve. We generated and characterized mouse models with conditionally altered Notch signaling in endothelial or interstitial cells of aortic valve. Mice with inactivation of NOTCH1 signaling in VEC developed bicuspid aortic valve and valve stenosis. NOTCH1 signaling in VEC was required for repressing proliferation and activating apoptosis of VIC after endothelial-to-mesenchymal transformation (EMT). We showed that NOTCH1 signaling regulated Tnfa expression in vivo and Tnfa signaling was necessary for apoptosis of VIC and post-EMT development of aortic valve. We have now met the need of critical animal models and shown that NOTCH1-Tnfa signaling balances proliferation and apoptosis for post-EMT development of aortic valve. Our results suggest that mutations in its components may lead to bicuspid aortic valve and valve stenosis in humans.