University of Liverpool, UK
Castration resistant-prostate cancer is largely impervious to feather hormonal therapy and hence the outlook for patients is grim. Here we use an approach to attach the recently discovered Achilles heel. The experimental treatments established in this study are based on the recent report that it is the FABP5-PPARγ-VEGF signalling axis, rather than the androgen receptor activated pathway, played a dominant role in promoting the malignant progression of castration resistant prostate cancer cells. Treatments have been established in nude mice by suppressing the biological activity of FABP5 using a chemical inhibitor SBFI26 and a novel bio-inhibitor, dmrFABP5. Both inhibitors significantly supressed the proliferation, migration, invasiveness and colony formation of PC3-M cells in vitro. They also produced a highly significant suppression of both metastatic rates and average sizes of primary tumours developed from cancer cells implanted orthotopically into the prostate gland of the mouse. Strikingly, the bio-inhibitor dmrFABP5, amutated FABP5 incapable of binding to fatty acids, produced a much better suppression of both primary tumour and metastasis. Both inhibitors interfere with the FABP5-PPARγ-signalling pathway. SBFI26 can competitively bind to FABP5 and hence suppresses cellular fatty acid uptake. In contrast, dmrFABP5 can block the fatty-acid stimulation of PPARγ and prevent it activating the down-stream regulated cancer- promoting genes. This is an entirely novel experimental approach to treating castration-resistant prostate cancer and is completely different from current treatments that are based on androgen-blockade therapy.
Dr. Youqiang Ke finished his PhD in Leeds University and joined the Cancer & Polio Research Laboratories in Liverpool University in 1989 to work as a Postdoctoral Research Associate. In 1994, Dr. Ke got a lecturer position in the Department of Pathology in the same university and started his research work on the molecular mechanisms involved in the malignant progression of prostate cancer cells. Dr. Ke was promoted to a Senior Lecturer in 2001, a Reader in 2003 and a Full Professor in 2005. Dr. Ke is the Director of Molecular Pathology in the School of Cancer Studies, Liverpool University, United Kingdom.
RegenerAge International and Westhill University School of Medicine, Mexico
As it has been previously demonstrated that co-electroporation of Xenopus laevis frog oocytes with normal cells and cancerous cell lines induces the expression of pluripotency markers, and in experimental murine model studies that mRNA extract (Bioquantine purified from in-tra- and extra-oocyte liquid phases of electroporated oocytes) showed potential as a treatment for a wide range of conditions as Squint, Spinal Cord Injury (SCI) and Cerebral Palsy among others. The current study observed beneficial changes with Bioquantine administration in a patient with a severe SCI. Pluripotent stem cells have therapeutic and regenerative potential in clinical situations CNS disorders even cancer.
One method of reprogramming somatic cells into pluripotent stem cells is to expose them to extracts prepared from Xenopus laevis oocytes. We showed previously that coelectroporation of Xenopus laevis frog oocytes; with normal cells and cancerous cells lines, induces expression of markers of pluripotency. We also observed therapeutic effects of treatment with a purified ex-tract (Bioquantine) of intra- and extra-oocyte liquid phases derived from electroporated X. laevis oocytes, on experimentally induced pathologies including murine models of melanoma, traumatic brain injury, and experimental skin wrinkling induced by squalenemonohydroperoxide (Paylian et al, 2016). The positive human findings for spinal Cord Injury, and Cerebral Palsy with the results from previous animal studies with experimental models of traumatic brain injury, respectively (Paylian et al, 2016). Because of ethical reasons, legal restrictions, and a limited numbers of patients, we were able to treat only a very small number of patients. These results indicate that Bioquan-tine may be safe and well tolerated for use in humans, and deserves further study in a range of degenerative disorders. We propose that the mechanism of action of Bioquantine in these various diseases derives from its unique pharmacology and combinatorial reprogramming properties.
In conclusion, these preliminary findings suggest that Bioquantine is safe and well tolerated on patients with Cerebral Palsy and-Spinal Cord Injury, among others. In addition to the regenerative therapy and due to the patient condition, we decided to include the Restore-Sensor SureScan. Based on the electrical stimulation for rehabilitation and regeneration after spinal cord injury published by Hamid and MacEwan, we designed an improved delivery method for the in situ application of MSCs and Bioquantine in combination with the RestoreSensor SureScan.
Conclusions: To the present day the patient who suffered a total section of spinal cord at T12-L1 shows an improvement in sensitivity, strength in striated muscle and smooth muscle connection, 11 months after the first therapy of cell regeneration and 3 month after the placement of RestoreSen-sor at the level of the lesion, the patient with a complete medullary section shows an evident improvement on his therapy of physical rehabilitation on crawling from front to back by himself and standing on his feet for the first time and showing a progressively important functionality on the gluteal and legs sensitivity1.
Dr. Joel I Osorio is the CEO and Founder - Biotechnology and Regenerative Medicine at RegenerAge International, Vice President of International Clinical Development for Bioquark, Inc., and Chief Clinical Officer at ReAnima™ Advanced Biosciences. Westhill University School of Medicine, Mexico. Joel I Osorio is an Advance Fellow by the American Board of Anti Aging and Regenerative Medicine (A4M). Dr. Joel was a Visiting scholar at University of North Carolina at Chapel Hill (Dermatology) He was a Fellow in Stem Cell Medicine by the American Academy of Anti-Aging Medicine and University of South Florida.
1Department of Translational Medicine, Lund University & Skane University Hospital, Sweden
2Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden
3Department of Laboratory Medicine, Lund University, Sweden
Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. Cyclooxygenase-2, having a key role in the biosynthesis of prostaglandin E2 (PGE2), is often up-regulated in CRC. PGE2 induces angiogenesis and tumor cell survival, proliferation and migration. The tumor suppressor 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is a key enzyme in PGE2 catabolism, converting it into its inactive metabolite 15-keto-PGE2 and is often down-regulated in cancer. Interestingly enough, CRC patients expressing high levels of Cysteinyl leukotriene receptor 2 (CysLTR2) have good prognosis and therefore, we investigated a potential link between CysLTR2-signaling and the tumor suppressor 15-PGDH in colon cancer cells.
We observed a significant up-regulation of 15-PGDH after LTC4 treatment, the ligand for CysLTR2, in colon cancer cells, on both mRNA and protein levels, which could be reduced by a CysLTR2 antagonist or a JNK inhibitor. LTC4 induced 15-PGDH promoter activity via JNK/AP-1 phosphorylation. Furthermore, we also observed that LTC4 via CysLTR2/JNK-signaling pathway increased the expression of the differentiation markers sucrose isomaltase and mucin-2 in colon cancer cells.
Restoration of 15-PGDH expression through CysLTR2-signaling promotes differentiation of colon cancer cells, indicating an anti-tumor effect of CysLTR2-signaling.
Dr. Shakti Ranjan Satapathy is a postdoctoral researcher at Department of Translational Medicine, Lund University, Sweden where he studies the role of Cysteinyl leukotriene receptors in metastasis of colon cancer. He started his postdoctoral research at Purdue University, USA where he studied the role of novel kinases as potential therapeutic targets for prostate cancer and Alzheimerʼs disease. He had received his PhD in Cancer nanotechnology in 2015 from KIIT University, India. Apart from his curiosity in life sciences, he is very fond of physics and world history. Dr. Shakti is committed to advance the understanding about cancer and making the world a better place.
President of OTR3, France
The importance of extracellular matrix (ECM) integrity in maintaining normal tissue function is highlighted by numerous pathologies and situations of acute and chronic injury associated with dysregulation or destruction of ECM components. Heparan sulfate (HS) is a key component of the ECM, where it fulfils important functions associated with tissue homeostasis. Its degradation following tissue injury disrupts this delicate equilibrium and may impair the wound.
Healing process: ReGeneraTing Agents (RGTA®s) are polysaccharides specifically designed to replace degraded HS in injured tissues. The unique properties of RGTA® (resistance to degradation, binding and protection of ECM structural and signalling proteins, like HS) permit the reconstruction of the ECM, restoring both structural and biochemical functions to this essential substrate, and facilitating the processes of tissue.
Repair and Regeneration: Furthermore, combined with cell therapy, RGTA® will participate in the regeneration process by providing a niche for cell homing. Several polymers have been tailored for specific tissues.
Here, we review 25 years of academic and company research surrounding this HS mimic, supporting the mode of action, preclinical studies and therapeutic efficacy of RGTA® in the clinic. With over 50 000 patients treated for the first two products on the market, for skin and cornea injury, with randomized controlled trials supporting the first pilot studies and with a pipeline for several RGTA® based product and an example of translational research from academy to industry.
Dr. Denis Barritault is graduated in Physics, completed his PhD in biochemistry in Paris University. And is a Post doctoral in molecular immunology at Pasteur Institute and NYU as NIH Fogarty Fellow he joined INSERM unit in Paris as developmental biologist. He made the first description and patents of FGF extracted from retina in 1979 and 82 as skin and cornea healing agent, became full professor at Paris-Est University in 1985, founded and directed a CNRS Laboratory on cell and tissue regeneration until 2003. He is now President of OTR3, Emeritus professor, honorary director of CRRET laboratory, a CNRS unit and author in over 200 publications and 30 patents
William Beaumont Institute for Stem Cell and Regenerative Medicine, Oakland University, USA
Perinatal tissues are non-invasive, primitive and abundant sources of stem cells (SCs) that have increasingly gained attention since they do not pose any ethical or moral concerns. Current methods to isolate SCs from these perinatal sources yield low amounts of cells with variable proliferation potential. We have investigated the properties of SCs isolated from cord blood (CB), discrete regions of umbilical cord (UC) such as cord lining (CL), Whartonʼs jelly (WJ), and cord-placenta junction (CPJ), chorion (CH) and fetal placenta (FP). CB had predominantly two types of SCs, adherent mesenchymal stromal/stem cells (MSCs), and non-adherent hematopoietic stem cells (HSCs). HSCs were CD 34+ and were negative for MSC surface markers. The isolated cells from all other sources were adherent MSCs. All MSCs had fibroblastoid morphology and were CD29+, CD44+, CD73+, CD90+ and CD105+ similar to that of the bone marrow (BM) derived MSCs.
We then investigated the therapeutic potential of MSCs to treat degenerative diseases such as degenerative disc disease (DDD) and retinal degenerative disease (RDD) using animal models. MSCs and their chondrogenic derivatives significantly improved the histology, cellularity, extracellular matrix protein, and in water and glycosaminoglycan contents in IVDs recipient of chondroprogenitors (CPCs) or NP-like cells (NPCs). The transplanted cells were functionally active as they expressed human genes and proteins, SOX9, ACAN, COL2, FOXF1, KRT19, PAX6, CA12 and COMP implicated in NP biosynthesis. These studies suggested involvement of TGFβ1 pathway in regulating NP regeneration. Therapeutic potential of UC-MSCs to treat DDD and other degenerative diseases as well as the challenges and new opportunities will be discussed in the presentation.
Dr. G Rasul Chaudhry, Ph.D., Professor of Molecular Biology and Co-Director, Oakland University William Beaumont Institute for Stem Cell and Regenerative Medicine, Oakland University, USA. His research focuses on the molecular regulation of genes involved in stemness, potency, and differentiation of embryonic, adult and perinatal stem cells. He is also interested in tissue bioengineering, mechanisms of diseases processes, public cord banking, stem cell-based therapeutic applications, biomaterials, toxicology, and drug discovery. His research has been funded by organizations such as National Science Foundation, USDA, USEPA, Beaumont Health, St. John Providence hospital, Michigan Head and Spine Institute. He published numerous original and review papers on a wide variety of research problems and recently on stem cells. He serves as a reviewer or member on the editorial board of various journals as well as on advisory review panels of national and international funding agencies.
SRM University, India
Traumatic brain injuries (TBIs) are a major cause of disability and death worldwide. They are clinically subdivided into mild, moderate and severe forms, mild TBI (also known as concussion) accounts for 80–90% of cases. The use of stem cells for treating traumatic brain injury (TBI) or concussion presents a highly viable therapeutic strategy. In particular, using an adult mesenchymal type stem cell (MSC) as a delivery mechanism for delivering therapeutic molecules has a tremendous potential since MSCs secrete endogenous anti-inflammatory and neuro-regenerative molecules. Dental pulp stem cells show close resemblance with mesenchymal stem cells and can differentiate into adipocytes and osteoblasts. In this study, we have successfully cultured stem cells from dental pulp isolated from surgically extracted third molar with a high percentage of mesenchymal population demonstrated by expression of surface markers, CD29, CD44, CD146 and Stro1. Whole genome transcriptome sequencing revealed that DPSCs were closely related to bone marrow derived mesenchymal stem cells. We have also identified presence of many neuro-beneficial proteins expressed by dental pulp derived mesenchymal stem cells such as; Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and gonadotropin-releasing hormone 1 (GnRH1). The activity of these neuro-beneficial proteins is further increased by the presence of immune-modulating proteins such as interleukins (ILs), transforming growth factor beta 3 (TGFB3), insulin-like growth factor 2 (IGF2), intercellular adhesion molecule 3 (ICAM3). Also, DPSCs secrete a large subset of the heat shock proteins which may act as chaperones and prevent tauopathy caused by the misfolding of phosphorylated tau protein, observed both in traumatic brain injuries (TBI) and in chronic traumatic encephalopathy (CTE). We propose that these beneficial trophic factors secreted from autologous dental pulp as a potential therapy for TBIs.
University of Calcutta, India
Background: Idiopathic Pulmonary Fibrosis is characterized by excessive matrix deposition that disrupts the normal architecture of the lung parenchyma and causes airway remodeling. It is a progressive and fatal lung disorder with high mortality rate. The current treatments provide only minimal benefits and have significant side effects, highlighting the need for novel treatment approaches to Pulm onary Fibrosis.
Objective: The aim of this study was to investigate the therapeutic potential of umbilical cord derived MSC (uMSC) bleomycin induced fibrosis.
Methods: A mouse model of bleomycin induced pulmonary fibrosis was used in the study. Wharton jelly derived mesenchymal stem cells were injected intravenously and inflammation, fibrosis and regeneration was examined using a series of assays such as assessment of total cell count, inflammation, hydroxyproline, cell proliferation and clonogenic potential and histology.
Results: We found in an increase in the total cell count (p < 0.001) and collagen content and a decrease in clonogenic potential (p <0.01) in the lung after bleomycin treatment as compared to the control group. Interestingly, intravenous administration of umbilical cord derived MSC showed reversal of these effects by decrease in collagen content, a decrease in total inflammatory cell count (p <0.01) and increase in clonogenic potential (p < 0.05) in the lung. Upon umbilical cord derived MSC administration, reactive oxygen species and reactive nitrogen species generation in the lung decreased as compared to only bleomycin treated group. Histological study of bleomycin treated lung revealed extracellular matrix decomposition, abnormal collagen degradation and distorted lung morphology compared to control groups; stem cell treatment assisted in restoration of lung morphology.
Conclusion: The present research suggests that administration of umbilical cord derived mesenchymal stem cells led to reduction in inflammation and collagen content, increased proliferative ability of the cells and restored lung morphology. Thus these cells may be used for future reference to formulate effective therapeutic protocols in managing bleomycin induced IPF.
Dr. Ena Ray Banerjee is Professor of Zoology, University of Calcutta, India and leads the Translational Outcomes Research Group that focuses on Immunobiology and Regenerative Medicine, drug discovery studies and basic research, including development and validation of novel drugs (small molecules), herbal extracts (functional food), probiotics (nutraceuticals), novel antibody-mediated (camelid antibody) and cells (tissue engineering of stem cells from embryo, foetal and adult tissue) in inflammatory (asthma, colitis, fibrosis, dermatitis, arthritis etc.) and degenerative disease models. She has published extensively in premiere scientific journals and her publications are widely cited in “methods” volumes as well as “drug discovery” websites and portals.
Department of Urology, Hospital of Zhengzhou University, China
Method: The numbers of regenerated myelinated axons of the pelvic parasympathetic nerve (PPN), intravesical pressure (IVP), S100β and growth associated protein 43 (GAP43) expressions of 3 groups experimental rats including FK 1706 + ETS group, ETS group and the control were compared.
Results: In the FK1706 + ETS groups, 90% the rats showed that the frequency of FG labeled neurons was larger than the 3.5 cutoff value, 100% the rats showed that the frequency of FG-FB double-labeled neurons was larger than the 5.5 cutoff value (Table 1). Urodynamic analysis confirmed that the average maximum of IVP in FK1706 + ETS group reached 76.3% of the value in the control group. Their average number of myelinated axons of regenerated PPN reached 80% of the amount in the control group. The nerve regeneration-associated markers data obtained from West blot indicated that the expression level of S100β in FK1706 + ETS group was approximately 3-fold higher than that of ETS group (P< 0.05). The GAP43 expression level in FK1706 + ETS group was also significantly higher than that of ETS group (P < 0.05).
Conclusions: FK1706 effectively enhanced the nerve regeneration and bladder function recovery after end-to-side neurorrhaphy. This immunophilin ligand should be considered as a potential therapeutic agent for improving nerve regeneration and functional recovery after nerve injury and or neurodegeneration.
Keywords:FK 1706; End-to-Side Neurorrhaphy; Immunophilin ligands; Neurogenic bladder; Nerve regeneration.
National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), U.S. Department of Health and Human Services (HHS), USA
U.S. Government research and Government-funded academic research is vital to innovation of pharmaceuticals and medical devices. This research may complicate how rights to inventions can be used. The conflicting demands of research and the patent law can sometimes put scientific work at odds with effective patent protection. We will discuss issues faced by government agencies, academic institutions and potential industry partners that are considering engaging in technology transfer. We will discuss how such funding affects the right to exploit and to license IP. We will look at what government agencies and academic institutions could do to effectively secure IP rights that not only serve the public good but that are also attractive to investors, therefore increasing the likelihood of commercialization success.
Dr. Ami Gadhia is a Technology Transfer and Patenting Specialist at the National Center for Advancing Translational Sciences (NCATS), a Center within the National Institutes of Health (NIH), U.S. Department of Health and Human Services (HHS). Dr. Ami negotiates agreements that allow for collaboration and translation of research. Prior to NCATS, she worked at Johns Hopkins since 2007, where she lead a team of licensing professionals and managed her own docket of technologies, as a portfolio director for technology licensing. Dr. Ami is a certified licensing professional, is registered to practice before the U.S. Patent and Trademark Office, and is a member of the State Bar of Georgia.
Yale School of Medicine, USA
The BRCA2 (Breast Cancer Susceptibility 2) gene is a caretaker of genome integrity. Germline mutations in BRCA2 predispose to a high risk for ovarian and breast cancer. The BRCA2 protein plays an important role in repair of DNA double-strand breaks (DSBs) by homologous recombination. BRCA2 dysfunction results in genome instability including chromosome aberrations and an abnormal number of centrosomes. Centrosome amplification is a hallmark of tumors from BRCA2 mutation carriers and may be responsible for the origin of chromosome missegregation at mitosis and DNA aneuploidy found in these tumors. However, it remains an open question how BRCA2 regulates centrosome duplication and the consequences for tumor initiation and progression. Here, we present the generation of an isogenic inducible BRCA2 human cell line providing a model to study acute loss of the BRCA2 protein. We plan to measure centrosome number and how BRCA2 regulates the centrosome duplication checkpoint with the end goal of understanding tumor initiation and maintenance in BRCA2 mutation carriers.
Dr. Jimenez-Sainz Judit is a Postdoctoral Associate in the Jensen group in Therapeutic Radiology Department. Her current research involves biochemical and cellular-based approaches to prevent and unmask the initial steps in breast and ovarian cancer formation. She received her phd from Universidad de Valencia, Spain and UCL, London. She is a member of ECUSA, NYAS and WISAY and she strongly believes in supporting new generation of students in STEM.
University of Helsinki, Finland
Date palm (Phoenix dactylifera L.) is widely grown in the hot arid regions, and provides nutrition, as a staple food for centuries, food security, and raw material to the food industry. Even though date fruits are rich in nutrition, minerals, sugar and phytochemicals and its global market share is extremely low. Date fruit is a rich source of sugar, nutrients and pharmaceutical secondary metabolites, and provide 3150 calories per kilogram, and contain a high percentage of carbohydrate (total sugars, 44/88%), fat (0.2 /0.5%), 15 salts and minerals, protein (2.3 /5.6%), vitamins and a high percentage of dietary fibre (6.4 /11.5%). They contain calcium, magnesium, phosphorus, potassium, iron, zinc, copper, manganese, selenium, vitamins A, A1, B, B1, B2, B3, B5, B6, and C as well as a variety of amino acids. The seeds contain aluminum, cadmium, chloride, lead and sulphur in various proportions. Date fruits have protective property against chronic diseases, which is attributed to phytochemicals. They have antioxidant activity, cholesterol-lowering properties, chemoprevention of cancer, prevention of diabetes, and cardiovascular diseases. Date fruits contain many classes of bioactive components including carotenoids, polyphenols especially phenolic acid, isoflavons, lignins, and flavonoids, tannins, and sterols. In date palm cultivars, phytosterols are in abundance in shoot tips and pollen grains, calli and somatic embryos Thin layer chromatography revealed a number of phytosterols including cholesterol, beta-sitosterol and stigmasterol, which are beneficial as anti-inflammatory, anti-atherogenicity, and anti-cancer Fresh date fruits are an excellent source of energy and remedy for alcoholic intoxication, stimulation of the uterus by regulating contractions, and treatment of constipation, However, more detailed work is needed for the identification, characterization, and quantification of phytochemicals in different date varieties at different stages of fruit ripening; systematic studies on the date health benefits and hardly recognized as a healthy food, and this aspect will be highlighted.
Dr. S Mohan Jain received M. Phil, 1973 and Ph.D., 1978, Jawaharlal Nehru University, New Delhi, India. He was postdoctoral fellow in Israel, and USA; visiting Professor in Japan and Italy; Technical Officer, International Atomic Energy Agency (IAEA), Vienna, Austria, 1999-2005. He is a consultant, serves on the editorial Board of several international journals; published 150 papers in peer reviewed journals, book chapters, and conference proceedings, and edited 50 books; invited speaker and acted as a Chair person in several international conferences worldwide. He was awarded Nobel Peace Prize, 2005, in commemoration the awarding to IAEA of the Nobel Peace Prize for 2005.
Director of research, Riordan Clinic, USA
The use of ascorbate in oncology has long been passionately debated. Vitamin C has been shown to protect against oxidant injury at physiological concentrations and has been suggested as having both a preventative and therapeutic role in a number of pathologies when administered at pharmacological levels. We presented the summary of our and other researchersʼ studies that has included in vitro and animal experiments, pharmacokinetic analyses, clinical trials and analysesof the effect of ascorbic acid in monotherapy and as adjuvant of conventional therapy in the treatment of cancer patients.
The rationales for using high-dose ascorbate infusions to treat cancer can be summarized as follows: high dose vitamin C is preferentially toxic to cancer cells, inhibits angiogenesis, improves patient well-being, decreases the markers of inflammation and tumor growth and reduces the side effects of chemotherapy. Clinical studies are ongoing in pancreatic cancer, ovarian cancer, prostate cancer and several types of other cancers. Ascorbate has the advantage of being low-toxic, which is now well documented by more than 10 clinical trials. Its efficacy has been demonstrated in preclinical and clinical trials when paired with standard radiation and chemotherapy regimens.
Clinical studies of chemotherapy with vitamin C demonstrated that intravenous vitamin C (IVC) does not interfere with antitumor effects of chemotherapy. IVC may improve time to relapse, enhance reductions in tumor mass and improve survival in combination with chemotherapy. IVC treatment improves quality of life, physical function, and toxicities associated with chemotherapy. The mechanisms underlying the preferential toxicity of vitamin C in cancer cells are not well understood. Several mechanisms are proposed that include the alterations of redox balance and cell metabolism, downregulation of several gene expressions that are involved in cancer proliferation, survival and angiogenesis, boosting immune system, strengthening the collagen structure, and inhibition of hyaluronidase. Available data provide a solid scientific rationale for the continued investigation of parenteral ascorbate as a chemotherapeutic agent.
Dr. Mikirova is director of research at the Riordan Clinic. After 15 years as the senior researcher at the Institute of Bio-Medical Problems in Russia, she joined the Riordan Clinic in 1997. Her efforts have included in vitro studies, animal studies, pharmacokinetic analyses, and clinical studies. She has published numerous articles including more than 50 in the area of the translational cancer medicine and 50 articles in the field of bio-medical aspects of radiation. Her areas of research focus include: effect of high dosage intravenous vitamin C on inflammation, cytokines, angiogenesis, gene expression and viral infection; potential of using high dose IVC alone or as the adjuvant therapy to treat cancer; and energy metabolism and functioning of mitochondria in cancer and normal cells.
Bogazici University, Turkey
Catheter based approaches have revolutionized the treatment of cardiovascular diseases. Nowadays, interventional cardiac trans-catheter therapies are targeting more complex pathologies, but X-ray fluoroscopy is not a sufficient medical imaging modality due to its poor soft tissue contrast. On the other hand, Magnetic Resonance Imaging offers ionizing radiation-free imaging modality with increased soft tissue contrast and unconstrained imaging planes but suffers from a lack of dedicated MRI compatible interventional devices for cardiac procedures. This presentation will highlight novel MRI compatible and visible interventional device technologies and also will introduce pre-clinical complex cardiovascular applications such as ventricular septal defect repair, cardiac biopsy and trans-catheter aortic valve implantation under MRI.
Dr. Ozgur Kocaturk is Associate Professor at Bogazici University, Institute of Biomedical Engineering Istanbul, Turkey.
1Harvard Medical School, USA
2Monash Biomedicine Discovery Institute, Australia
3The University of Texas at Austin, USA
4Weill Cornell Medicine, New York, USA
5Harvard Medical School, USA
ESCs are capable of indefinite self-renewal and differentiation into all lineages. Although much has been learned, the components that establish and maintain ESC state/identity are incompletely defined. In this study, we took a high-throughput CRISPR-Cas9 mediated gene editing functional genomics approach to study the functions of 324 epigenetic regulators in mouse ESCs, for its identity. We designed 6 single guide RNAs (sgRNAs) that target coding sequences of per epigenetic genes. This produced a library of ~1938 sgRNAs. The library also included 127 non-targeting sgRNAs as negative controls, as well as 119 sgRNAs targeting GFP (of the Oct4-GFP reporter) and 150 sgRNAs targeting coding sequence of mESC-TFs as positive controls. This “epigenetic pooled library” comprises all sgRNAs that were synthesized, cloned into a lentiviral vector and transduced in Oct4-GFP reporter (OCT4 is the master regulator of ESCs) mESCs, which constitutively expressed Cas9. Most importantly, transduction was done at low multiplicity to ensure that nearly all selected cells contain one sgRNA. The GFP-low/ GFP-negative and GFP-high cells were sorted; genomic DNA was isolated and deeply sequenced to enumerate sgRNAs present. An “enrichment score” was calculated by comparing sgRNA frequency in the GFP-low/GFP-negative cells over to GFP-high cells. Enrichment for each sgRNAs was scored to their corresponding epigenetic genes, as candidates. The list of novel candidate epigenetic genes was functionally validated through secondary screens. Finally, we selected two epigenetic regulators- TAF5L and TAF6L, part of the Histone Acetyltransferase (HAT) complex, for further mechanistic studies. Currently, we are using multidirectional biochemical, genetics, molecular and genomics approaches to understand the detailed mechanism by which TAF5L and TAF6L control ESC state. Altogether, I anticipate, this comprehensive study will reveal new important epigenetic regulators and their detailed functions for ESCs state.
Dr. Partha Pratim Das did his Masters in Molecular Biology from International Max Planck Research School, Gottingen, Germany. He has done his PhD with Prof. Eric Miska to study-Role of short RNAs/piRNAs in Caenorhabditis elegans germline development at Gurdon Institute, University of Cambridge, UK. For post-doctoral research, he joined Prof. Stuart Orkinʼs laboratory at Harvard Medical School to study how chromatin changes regulate transcriptional gene regulation in embryonic stem cells (ESCs). He recently started independent lab at Biomedicine Discovery Institute, Monash University. His present and future interest of studies elucidate how epigenetic and epi-transcriptomic changes regulate gene expression in ESCs and differentiated cells under normal and pathological conditions.
Duquesne University School of Nursing, USA
Fragmentation of physical, mental, and chemical dependency care delivery systems has led to significant gaps in care for individuals with severe mental illness and substance use disorders. A shifting international focus to chronic illness and the default provision of mental health care demands new approaches. In the US, the rise in numbers of those identified with mental health conditions has risen, while the resources to care for those patient have declined, creating a gap in service to a vulnerable population. This DNP project is a program evaluation of an integrated behavioral health and mental health program provided by a Patient Cantered Medical Home Primary Care Clinic. This DNP Projectʼs purpose was to evaluate the impact of the implementation of integrated behavioral and mental health services within a primary care clinic on patientʼs adherence to the treatment plan, staff and patient experiences and cost of care for patients with severe mental illness. Qualitative and quantitative data was collected 12 months prior to and after the program change which included the addition of a licensed mental health expert and workflow adjustments. Upon completion of data collection and analysis, results showed that the integration of mental health into primary care has had a positive impact on patient adherence to treatment, patient satisfaction and staff satisfaction.
Dr. Paulette Sides Sasser has completed her Doctorate in Nursing Practice from Duquesne University with a focus on the integration of mental health into primary care systems. During her 25 years in the fields of mental health and primary care she has worked as a graduate school faculty, and manager of community, emergency, and forensic mental health programs. She acted as a clinical expert for the National Medicare Reimbursement Pilot for the United States. She has also presented topics in ambulatory nursing, reimbursement, primary care, and mental health at national and international conferences.
Shanghai Institute of Biochemistry and Cell Biology, China
Skeletal muscle regeneration involves a series of physical responses after injury or disease, including activation of quiescent satellite cells (muscle stem cells), proliferation of satellite cells and myoblasts, differentiation of myoblasts, and formation of new myofibers. In recent years, more and more evidences suggested that inflammation plays important roles during muscle regeneration process. However, how inflammation affects muscle regeneration remains to be elusive. Here we focused on T cells mediated inflammation and found that it is a required positive regulator at early stage of skeletal muscle regeneration. Upon muscle injury, we observed large amount of T cell infiltrated at injury site. In immunodeficient mice, where the T cell infiltration is diminished while other liphocytes such as macrophage infiltration remains normal, reparation of muscle injury was dramatically delayed. To further investigate the mechanism of T cell promoting muscle regeneration, we characterized the protein profile of activated T cells. A combination of four factors was identified to be able to promote satellite cell proliferation and long term expansion dramatically in culture. The cultured expanded satellite cells continue to express muscle stem cell marker, and were able to regenerate functional myofiers in vivo. Furthermore, muscular injection of the four factor cocktail could rescue the muscle regeneration defects caused by T cell deficiency. Our results demonstrate that T cell mediated inflammation is required for muscle stem cell proliferation at early stage of post-injury regeneration.
Dr. Ping Hu, Ph.D. is a Principal Investigator in Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences. She graduated from Peking University and obtained her Ph.D. degree from the joint graduate program of State University of New York, Stony Brook/Cold Spring Harbor Laboratory. She performed her postdoc research in University of California, Berkeley/Howard Hughes Medical Institute. Hu Lab is focused on the regulation of muscle stem cell functions and myogenesis, especially on the microenvironment of muscle stem cells and the epigenetic regulation of muscle stem cell functions.
Karolinska Institute, Sweden
Placental amnion tissue has been used for decade in clinical practice, while amnion--derived cells has been proved successful only recently. We reported that human amnion epithelial cells (hAEC) from term placenta are not tumorigenic, have immunomodulatory and anti-inflammatory properties and once transplanted differentiate into functional hepatocyte-like cells. In preclinical studies with immune-competent mice, hAEC engrafted and survived without administration of immunosuppressive drugs, resulting in correction of metabolic liver diseases (iMSUD and PKU) and reversal of acute liver failure. Immunogenicity of the hAEC has been confirmed on purified immune effector cells (T-, B- and NK-cells).
Placental expression of non-canonical HLA proteins has been identified as key regulator in maternal-fetal immune-toleration. Amnion characteristically lacks HLA class 2 expression, and expresses both class 1a and 1b. We measure HLA-G and HLA-E expression both as membrane-bound and soluble isoforms. Recently, purinergic mediators, such ATP and NADPH, hydrolyzed by plasma membrane nucleotidases, have been identified to regulate immune cell response. High level expression of ecto-enzymatic axis and non-canonical HLA molecules likely play a key role in immunological tolerance and long-term acceptance of the human xeno-cell graft in immunocompetent mice. Based on their safety and the successful preclinical studies, approval was granted to begin banking of hAEC under cGMP condition at Karolinska Institute, and to perform hAEC transplants on 10 patients with liver disease without immunosuppression.
Dr. Roberto Gramignoli, PhD, is presently is an Assistant Professor at Karolinska Institute, Department of Laboratory Medicine Stockholm, Sweden. From May 2012 - Dec 2014 he obtained Postdoc Position in Karolinska Institute, Department of Laboratory Medicine Sweden. From Jul 2007 - Apr 2012 he was a visiting fellow at University of Pittsburgh, Department of Pathology Pittsburgh, United States. And from Nov 2002 - May 2008 he was a research fellow at Fondazione IRCCS Caʼ Granda - Maggiore Policlinico Hospital, Regenerative Medicine Area (Riparazione e Sostituzione di Cellule, Organi e Tessuti) Milano, Italy. In Apr 2000 - Jul 2002 he was an undergraduate student, from National Research Council, Milan, Italy.
Dr. Robertoʼs primary interest has always been to investigate human liver biology, pathology and disease; in particular, human liver cells (hepatocytes) transplantation as an alternative treatment to liver diseases. Gramignoliʼs group was the first facility approved for clinical HTx, and they performed infusions in patients with metabolic liver diseases. His group optimized methods to isolate human hepatocytes in GMP conditions; they identified several roadblocks that prevent a more successful implementation of HTx, including paucity of human hepatocytes. They investigated alternative sources, such as fetal liver cells, iPS and placental amnion epithelial (AE) cells. Encouraged by the lack of tumorigenicity and the expression of genes that could correct human metabolic liver diseases, in addition to immunomodulatory and anti-inflammatory effects, Gramignoliʼs group proved efficacy of human AE cells in several preclinical models, leading to AE cell banking for clinical purposes.
Skills and Expertise:
Cell Culture Molecular Biology, Cell Biology Tissue Engineering, Gastrointestinal Diseases, Stem Cell Biology, Liver Diseases, Clinical Trials, Regenerative Medicine, Hepatocellular Carcinoma, Stem Cells, Liver Cirrhosis, Liver Cirrhosis Hepatobiliary, Surgery Liver Transplantation, Transplantation Biliary Tract Diseases, Liver Surgery Pancreatic Diseases, Hepatitis Liver Failure Cholangiocarcinoma, Liver Diseases and Immunology, Pluripotent Stem Cells, Embryonic Stem Cell, Liver Regeneration Cell Therapy, Transplant Surgery, Cell Transplantation, Radiofrequency Ablation, Hepatocytes Stem Cell Therapy, RFAH epatoblastoma.
Yale Center for Genome Analysis (YCGA), Yale University, USA
The Yale Center for Genome Analysis (YCGA) is a state-of-the-art DNA Sequencing Center launched in 2010 to provide an open access centralized facility for genomic analysis, equipment and expertise required for carrying out large-scale sequence analysis studies (http://ycga.yale.edu/). Our group foresaw the scientific opportunities for the development and use of exome sequencing in Mendelian genetics and was the first to develop the method for exome capture on the NimbleGen/Roche platform. We were also the first to demonstrate the biological utility of exome sequencing for clinical diagnostic and translational applications. Over the last couple of years, exome sequencing approach developed by us has identifieddisease causing variations from wide variety of phenotypes that has broadened understanding of the underlying biology linking mutations to human phenotypes. In addition, it fueled the development of essential tools for diagnosing, preventing and treating both rare and common diseases in the clinical setting. In the past five years, we have successfully applied exome analysis approach to complete whole-exome sequencing and analysis of over 75,000 samples of a wide spectrum of phenotypes to identify hundreds of novel genes. The presentation will focus on overview of translational research, biomarker discovery efforts and precision medicine efforts at Yale.
Dr. Shrikant Mane completed his PhD at The University of Bombay and Postdoctoral studies from The Johns Hopkins University School of Medicine. He is the Professor of Genetics, Director of MBB Keck Biotech laboratory & Director of Yale Center for Genome Analysis, one of the most scientifically productive and accomplished Genome Centers. He has published more than 100 papers in reputed journals and has been serving as an ad hock reviewer of several journals. He is currently one of the principle investigators of a $12 million grant from NIH/NHGRI to establish The Yale Center for Genome Analysis
1Hospital Universitari Vall dʼHebron, Vall dʼHebron Research Institute (VHIR), Barcelona, Spain
2Universitat Autònoma de Barcelona, Barcelona, Spain
3Hospital Universitari Vall dʼHebron, Barcelona, Spain
4IIBB-CSIC-IDIBAPS, Barcelona, Spain
4IIBB-CSIC-IDIBAPS, Barcelona, Spain
5CIBER-BBN, (CIBER-BBN), Barcelona, Spain
Background: In Lupus Nephritis (LN), there is still a need to identify a biomarker to better monitor disease activity, guide clinical treatment and predict patientʼs long-term outcome. Several studies have suggested a possible role of Neuropilin-1 (NRP-1) in renal repair, therefore its relevance in predicting clinical response was investigated.
Methods: Urinary NRP-1 expression and protein levels were evaluated in two cross-sectional cohorts of patients with biopsyproven LN (N=45 and 25) and in three controls cohorts (N=25 for each). Thirty-eight (54%) patients from the combined cohorts achieved complete remission following standard therapy in a median time of 18.5 months. A prospective cohort of LN (N=39) was used to evaluate the changes of NRP-1 levels over time.
Results: Significantly higher urinary NRP-1 levels in patients with active LN compared with control groups were found. Patients who achieved complete response had high urinary and tissue NRP-1 levels at the time of renal biopsy (p<0.001 and p<0.01, respectively). Areas under the receiver operating characteristic curve, comparing baseline creatinine, proteinuria, urinary NRP-1 and VEGFA protein levels, showed NRP-1 levels to be an independent predictor factor for clinical response (AUC 0.8384, p=0.003). By longitudinally tracking patients, we found that NRP-1 levels remained markedly increased in the patients with complete response (median levels 1112 ng/mg Cr, p=0.003).
Conclusions: These findings indicate that urinary levels of NRP-1 may predict clinical response and could be used as an early biomarker for the prognosis of therapy response in lupus nephritis patients.
Dr. Cristina Sole obtained her PhD in chemistry and biochemistry in Rovira Virgili University (Tarragona, Spain) with 12 publications. She was in the Molecular Biology Department of the Island Balearic University (Mallorca, Spain), in the Reading University with Dr. Katja Strhohfeldt (UK), in Durham University with Prof. Andy Whitting (UK) and in Anacor Pharmaceutical Company (Palo Alto, California, USA). In 2014, she received a post-doctoral grant to work with Lupus Unit with Dr.Ordi in Vall dʼHebron Institute Research (VHIR, Barcelona). She is currently interested in translational research based on urinary biomarkers in lupus nephritis and molecular mechanism of action in cutaneous lupus.
The McGowan Institute of Regenerative Medicine, University of Pittsburgh, USA
Extracorporeal CO2 removal represents an effective treatment strategy for patients with acute and acute-on-chronic respiratory insufficiency. The technology holds the most promise as a means of avoiding intubation and mechanical ventilation in patients with an acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD), and as a means of allowing for lung protective ventilation in patients with Acute Respiratory Distress Syndrome (ARDS). Unlike oxygen supply, carbon dioxide can be removed at therapeutic levels from blood at relatively low extracorporeal blood flowrates, similar to those used in acute hemodialysis. To do so effectively, a novel integrated artificial lung and blood pump system called the Hemolung® Respiratory Assist System (RAS) has recently been developed and commercialized. The talk will describe the early design and development work leading to the Hemolung RAS, and features which distinguish it from other systems focused on CO2 removal. Key results from recent animal and human clinical trials of the Hemolung RAS will be presented, along with current work on novel enzymatic coatings and other approaches being developed in the laboratory for next generation respiratory dialysis systems. For patients requiring oxygenation in addition to CO2 removal, the Medical Devices Laboratory at the University of Pittsburghʼs McGowan Institute of Regenerative Medicine is developing wearable artificial lungs for adults and children as a bridge to lung transplant or lung recovery. Bench and animal studies of these technologies will be presented along with the vision on how the next generation of wearable artificial lungs will evolve to provide both low blood flow CO2 removal, along with higher blood flow oxygenation in an integrated platform. The challenges of spinning out technology from a university laboratory and commercializing that technology through a startup company, ALung Technologies, will also be discussed.
Dr. William J Federspiel received his PhD in 1983 in Chemical Engineering from the University of Rochester and currently is the William Kepler Whiteford Professor of Bioengineering in the Swanson School of Engineering at the University of Pittsburgh, with a secondary appointment in Critical Care Medicine. He is a Co-Founder of Alung Technologies, a Pittsburgh based medical device company that develops respiratory assist systems, and currently serves as Head of the Scientific Advisory Board for Alung. Dr. Federspiel is an elected Fellow of the American Institute of Medical and Biological Engineering (AIMBE) and the Biomedical Engineering Society (BMES). He has over 100 research publications and book chapters and holds numerous patents related to devices and methods for respiratory assist and inflammatory modulation. He directs research in the Medical Devices Laboratory, a core laboratory of the McGowan Institute for Regenerative Medicine.
University College London, UK
Farlanʼs talk will focus on the development of robust, reproducible and cost effective production processes in the emerging field of cell therapy. His team are establishing novel processing technologies which will underpin the commercialisation of these types of products. Their work uses a whole bioprocessing and ultra scale-down methodologies pioneered at UCL to ensure that new production process are considered as whole rather than individual operations in isolation. Farlanʼs group are developing new methods for the majority of steps involved in the production of cellular therapies. Current projects include the application of bioprocessing methodologies to (i) the expansion of stem cells, (ii) their directed differentiation into regenerative populations, (iii) the non-destructive dissociation of differentiated cellular aggregates into single cell suspensions, (iv) purification techniques for positive selection and (v) point-of-care processing which includes cryopreservation, shipping, thawing, washing and presentation of the final therapy ready for administration.
Dr. Farlan Veraitch gained his Ph.D. from the University of Birmingham where his research focused on the optimisation of mammalian cell culture processes. He then moved to UCL where he worked as a Post Doctoral Research Assistant on the automation of embryonic stem cell processing. Since gaining his lectureship, and subsequent senior lectureship, Farlan has helped to establish the UCLʼs Cell Therapy Bioprocessing programme which has been applying ultra scale-down, bioprocess modelling and a whole bioprocessʼ vision to the development of robust stem cell production processes.
1Experimental and Clinical Research Center, Charité – Universitaätsmedizin Berlin, and Max-Delbruck-Center for Molecular Medicine, Germany
2Berlin School of Integrative Oncology, Charité – Universitaätsmedizin Berlin, Germany
3Medical Department of Hematology, Oncology, and Tumor Immunology, and Molecular Cancer Research Center (MKFZ), Charité - Universitaätsmedizin Berlin, Germany
4German Cancer Consortium, German Cancer Research Center (DKFZ), Germany
5Department of Hepatology and Gastroenterology, Charité – Universitaätsmedizin Berlin, Germany
6Mathematical Modeling Group, Max Delbruck Center for Molecular Medicine, Germany
7Department of Nuclear Medicine, Charité - Universitaätsmedizin Berlin, Germany
8Berlin Experimental Radionuclide Imaging Center (BERIC), Charité - Universitaätsmedizin Berlin, Germany
9Piramal Imaging, Germany
MACC1, a master regulator of metastasis, is involved in most hallmarks of cancer, including deregulated metabolism. Fragmentary data on the role of MACC1 in gastric and hepatocellular cancers exist, whereas its role in colorectal cancer metabolism remains totally unknown. Here, we report a systematic analysis of MACC1-driven metabolic networks by elucidation of context dependent alterations of nutrient utilization, metabolic tracing using 13C-labeled metabolic substrates and flux analysis. In this context, the relation of MACC1 to the utilization of glucose, glutamine, pyruvate, lactate and palmitate metabolic substrates was investigated. Our results demonstrate that MACC1 exerts multiple effects on CRC cell metabolism, where most of them can be subdivided onto those which mediate increased nutrient depletion and those where MACC1 alters the metabolic pathways by affecting metabolite production or turnover from metabolic substrates. In particular, MACC1 was found to supportutilization,on multiple levels,of glucose, glutamine and pyruvate metabolic substrates in environment-dependent manner. Our results suggest that MACC1 is a novel regulator of cancer cell metabolism, and its targeting will affect cancer metabolic pathways thus leading to homeostatic imbalance and reduced cancer cell survival.
Inna Zaimenko is a PhD student at Charitè University Medicine & Max Delbruck Centre (from January 2015–Present), was a Student Research Assistant (December 2013 – November 2014) and Master thesis (April 2014 – October 2014) from DKFZ German Cancer Research Centre. She was a fellow from University of Tartu in April 2011 – May 2011. She obtained her Masterʼs Degree, Oncology and Cancer Biology from Heidelberg University.
She was awarded the PhD fellowship-Berlin School of Integrative Oncology (BSIO) at Charitè University Medicine, Master Study scholarship from German Academic Exchange Service (DAAD). And Travel Grant to attend FEBS Practical Course from Federation of European Biochemical Societies (FEBS). Certification from edX - Verified Certificate for Case-Study: RNA-Seq data analysis and for Making Science and Engineering Pictures: A Practical Guide to Presenting Your Work.
WideCells Group, UK
The term blood substitute is actually a misnomer because only a part of the total functions of the blood is replaced by any available so-called substitute, i.e., oxygen delivery and volume expansion only. Therefore, a more accurate term should be red cell substitute. Cord blood, because of its rich mix of fetal and adult hemoglobin, high platelet and WBC counts, and a plasma filled with cytokine and growth factors, as well as its hypoantigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood during emergencies due to any etiology of blood loss and anemia.
Our experience of 192 units of cord blood transfusion in patients with beta thalassaemia with severe anaemia (haemoglobin concentration varying from 3.5 to 6 g/dl with mean haemoglobin 4.67g/dl) proved to be extremely effective in 84 patients as an emergency substitute of adult RBC transfusion (male: female ratio 1:1, age varying from 6 months to 38 years). In the present series, the collection of the blood varied from 57 ml-136 ml mean 84 ml +/- 7.2 ml SD, median 87 ml, mean packed cell volume 45 +/- 3.1 SD, mean haemoglobin concentration 16.4 g/dl +/- 1.6 g/dl SD. After collection the blood was immediately preserved in the refrigerator and transfused within 72 hours of collection from the consenting mother undergoing lower uterine cesarean section.
We did not encounter a single case of immunological or non immunological reaction till date. We suggest that the medical fraternity use this precious gift of nature, which is free from infection, hypoantigenic with an altered metabolic profile, filled with growth factor and cytokine filled plasma with potential higher oxygen carrying capacity than for adult blood, as an emergency source of blood for the management of transfusion-dependent beta thalassemics.
Professor Peter Hollands PhD (Cantab), FRSB, Cbiol; trained at Cambridge University under the supervision of the co-inventor of IVF and Nobel Laureate Professor Sir Bob Edwards FRS. His PhD was in stem cell technology with a focus on the transplantation of stem cells from the developing fetus. His post-doctoral position was as a Senior Embryologist at Bourn Hall Clinic which was the first IVF clinic in the world. Peter has been the Scientific Director of Cells for Life in Toronto and Smart Cells in the UK and was HTA Designated Individual for Smart Cells. He has carried out research in stem cell technology and has written numerous papers and book chapters on stem cell technology. He has been an invited speaker to many international conferences including personal invitations to speak twice at the Vatican, the UK House of Lords and The Canadian Parliament. Peter also has experience in creating new stem cell technology laboratories and the related accreditation and regulatory aspects of stem cell laboratories. Peter currently works as the Group Chief Scientific Officer of the worldwide stem cell services company WideCells Group. Peter was awarded a Visiting Chair in Regenerative Medicine from Calcutta School of Tropical Medicine in November 2017.