Thursday, October 12, 2023
- 08:00 – 09:00 Registration | Poster Mounting
- 09:00 – 13:00 Management Committee Meeting | Hybrid format | MC members only. Chairs: Antonio Cuadrado, Spain, and Gina Manda, Romania
- 11:00 – 11:20 Coffee break
- 13:00 – 14:00 Lunch | Registration
- 14:00 – 16:00 Scientific Session I: NRF2 Regulatory Mechanisms Chairs: Anna-Liisa Levonen-Harju, Finland, and Elena Milanesi, Romania
Anna Grochot-Przeczek is an associate professor in the Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University in Krakow, Poland. She studies the molecular mechanisms that regulate the function of endothelial cells and blood vessels with a focus on NRF2/KEAP1 pathway, ageing and S-nitrosation. Currently, she investigates the importance of NRF2/KEAP1 imbalance and loss of proteostasis in the function of blood vessels.
Tugba Boyunegmez Tumer is currently Full Professor of Biochemistry at the Department of Molecular Biology and Genetics, at the Çanakkale Onsekiz Mart University, Turkey. She earned her MSc and PhD degrees from the Middle East Technical University, Turkey in 2004 and 2009, respectively. In 2013 and 2014, she worked as a post-doc researcher in NIH Funded International Research Training Center for Botanicals and Metabolic Syndrome, at Rutgers University, New Jersey, USA. Upon her return to Turkey, she was recruited to Çanakkale Onsekiz Mart University, where she has established a research team focusing on understanding the molecular effects of natural product-derived and synthetic small molecules on chronic inflammatory conditions and is working towards development of pharmacological lead compounds for prevention and treatment of chronic diseases particularly, cancer and neuroinflammation. Her lab combines in vitro/in vivo assays, multi
omic tools and in silico computation, modelling and ADMET approaches for rational lead discoveries.
Ana Čipak Gašparović is a Senior Research Associate in the Division of Molecular Medicine at the Ruđer Bošković Institute in Zagreb, Croatia. Her research focuses on the role of oxidative stress and antioxidative response in the resistance to cancer treatment. Recently, her research included aquaporins in breast and colon cancer. Special emphasis is given to peroxiporins, specific aquaporins which, in addition to water and glycerol, channel hydrogen peroxide, and as a consequence contribute to oxidative and antioxidative response of the cell. She is interested in the regulation of NRF2 pathway in response to peroxiporins, and their influence on the development of therapy resistance.
Hatice Esenkaya recently graduated with a PhD from the Department of Molecular and Cell Biology at the University of Leicester, UK, supervised by Professor Ian Eperon and Dr Cyril Dominguez, and working on RNA splicing. My recent research was studying the effects of the G-quadruplex stabilising ligand GQC-05 on alternative splicing of Mcl-1 pre-mRNA. My interests are in pre-mRNA splicing and the interaction between spliceosome proteins and RNA. I am particularly interested in how their interaction affect the outcome of alternative splicing. and if their interactions can be altered, using a variety of methods, to see if the splicing pattern can be shifted to obtain more favourable isoform.
Ana I Rojo. Ana I Rojo studied Biochemistry and Molecular Biology at the Autonomous University of Madrid (2001 and 2002), holds a PhD in Biochemistry (graduated in 2006), and since 2017 is professor in Biochemistry at the Autonomous University of Madrid (Faculty of Medicine). As professor, she has participated in multiple teaching activities for the degrees of Biochemistry, Medicine, and Nursing, with special focus on research training. She has been holder of different competitive fellowships and contracts. Her professional career is focused on the study of the molecular basis of neurodegenerative diseases and in the search for novel brain protective therapies with a special focus on redox biology and NRF2 transcription factor. Nowadays, she is exploring the role of NRF2 in the pathogenesis of Alzheimer’s disease and lateral amyotrophic sclerosis as principal investigator. She has published over 50 primary and review articles and participated in more than 30 congresses.
- 15:40 – 16:00 Coffee Break | Poster Viewing
- 16:00 – 18:00 Scientific Session II: NRF2 Monitoring, Drug Targets and Delivery Chairs: Monika Jakubowska, Poland, and Elke Heiss, Austria
Albena Dinkova-Kostova is a Professor of Chemical Biology at the University of Dundee School of Medicine (UK). She graduated in Biochemistry and Microbiology from Sofia University (Bulgaria) and obtained her PhD degree in Biochemistry and Biophysics from Washington State University (USA). She subsequently trained in Pharmacology at Johns Hopkins University School of
Medicine (USA), where she continues to hold an Adjunct Professor position. She joined the University of Dundee in 2007 as a Research Councils UK Academic Fellow. Her group collaborates with basic scientists and clinicians, and with the pharmaceutical industry. In her research, at the interface of Chemical Biology and Medicine, she is committed to understanding how cells and organisms respond to oxidative, inflammatory, and metabolic stress, and is working towards development of strategies for protection against chronic disease. She was named among the top influential academics in Clarivate’s Highly Cited Researchers 2019, 2020, 2021 and 2022 lists.
Sibel Kalyoncu Uzunlar graduated from Molecular Biology & Genetics and Chemistry departments in Boğaziçi University (Istanbul, Turkiye) with a double major in 2008. After receiving her master’s degree on Chemistry and Biological Engineering from Koç University (Istanbul, Turkiye) in 2010, she started her PhD at Georgia Institute of Technology (Atlanta, GA, USA). In 2016, she completed her doctorate with her studies in the fields of protein biochemistry and structure. Then, she started her postdoctoral research in the field of antibody engineering at Rensselaer Polytechnic Institute. Her research in the USA has been funded by both public (NIH, NSF) and industry (Novo Nordisk). Returning to Turkey in 2018, she established the Antibody Engineering laboratory as the research group leader at Izmir Biomedicine and Genome Center. By the help of government- and industry supported projects in her laboratory, she aims to develop innovative therapeutic/diagnostic products based on antibody, protein and enzyme engineering.
Enabling Precision: Chemogenetic Tools for Ultralocal Redox- and pH-Control in Nrf2 Pathways
Asal Ghaffari Zaki, Mohammad Miri, Şeyma Çimen, Emrah Eroğlu
Regenerative and Restorative Medicine Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul 34810, Türkiye
Email: emrah.eroglu@medipol.edu.tr
We present a pioneering chemogenetic advancement, focusing on a novel approach for ultralocal pH manipulation. Contrary to conventional understanding, we have revealed the intricate interplay between hydrogen peroxide (H2O2) and Nrf2 activation yet cellular pH in this relationship remains enigmatic. Our chemogenetic tools offer targeted enzyme-based pH modulation within subcellular compartments, enabling controlled pH dynamics. By exploiting these tools, we hope to open a new avenue for investigating Nrf2 signaling complexities. Our modest aim is to shed light on the potential of ultralocal pH manipulation and its impact on Nrf2-related studies.
Emrah Eroğlu serves as a Principal Investigator at Istanbul Medipol University and is the Deputy Director of the Research Institute for Health Sciences and Technologies (SABITA) in Turkey. With a background in biotechnology and molecular biology, his research primarily focuses on investigating intricate cellular processes at the single-molecule level. At Istanbul Medipol University, Dr. Eroğlu’s lab is at the forefront of developing genetically encoded biosensors and chemogenetic tools. These cutting-edge advancements enable the visualization of reactive oxygen and nitrogen species pathways in vascular cells, facilitating a deeper understanding of their roles in signaling cascades and neurodegenerative diseases. Having held significant positions at institutions such as Harvard Medical School and MedUni Graz, Dr. Eroğlu has garnered recognition through honors like the EMBO Installation Grant and the Leopold Flohé Redox Pioneer Young Investigator Award. He actively participates in scientific organizations (SFRR-E) and contributes to esteemed journals such as Redox Biology, FRBM, Redox biology biochemistry and chemistry.
Innovative Drug Delivery Platforms:
Tailoring Carbon Nano-onions for Targeted Therapeutic Applications
Silvia Giordani
School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland
Email: silvia.giordani@dcu.ie
Numerous challenges accompany conventional drug delivery methods, such as adverse side effects, multi-drug resistance, premature drug degradation, inadequate tissue penetration, and non-specific toxicity. Targeted delivery, employing nanocarriers as transport vessels for payloads, holds promise in mitigating these critical concerns. This strategy involves functionalising nanoparticles with targeting agents, which enables their selective uptake by cells that overexpress specific receptors, such that they can transport the therapeutic payload across the cellular membrane of target neoplastic cells. Consequently, this approach enhances drug concentration in the target cells while simultaneously reducing the exposure of healthy cells to the therapeutic agent.
In this oral presentation, carbon nano-onions (CNOs) will be introduced as a promising candidate for nanocarrier-based drug delivery systems. CNOs, also known as multi-layer fullerenes, comprise multiple concentric layers of sp2 hybridised carbon. Our research focuses on the synthesis and functionalisation of CNOs to investigate their potential in drug delivery. A novel CNO-based nanocarrier, incorporating hyaluronic acid— an optimised targeting agent—for the specific delivery of gemcitabine to cells overexpressing CD44 receptors has been developed in my lab (Fig 1). After examining CD44+ and CD44- human pancreatic adenocarcinoma (PDAC) cells, we observed that fluorescently labelled CNOs were selectively internalised by CD44+ cells, with no significant toxicity detected within a biologically significant concentration range. We demonstrate that CNOs possess low toxicity and could potentially be employed to deliver gemcitabine directly to CD44+-PDAC cells. Our results highlight this; the CNO-based nanocarriers demonstrated excellent in vitro outcomes in PDAC cells that are otherwise particularly difficult to treat due to various chemoresistance-pertinent factors.
Fig 1. Schematic of a CNO-based (grey) nanocarrier designed to deliver gemcitabine (green) to tumours via hyaluronic acid (orange) mediated targeting of cancer cells overexpressing CD44 receptors.
Silvia Giordani joined the School of Chemical Sciences at Dublin City University as Professor Chair of Nanomaterials in 2018. Previously she received her PhD in Chemistry from the University of Miami, USA and carried out postdoctoral research at Trinity College Dublin (TCD) and at the University of Trieste, Italy. In 2007 she received the prestigious President of Ireland Young Researcher Award and was a Research Assistant Professor at TCD from 2007 to 2013. In 2013 she founded and directed the new “Nano Carbon Materials” research lab at the Istituto Italiano di Tecnologia (IIT) and in December 2016 she was appointed Associate Professor in Organic Chemistry at the University of Turin, Italy. Her main research interests are in the design, synthesis, and characterization of a wide range of nanomaterials for applications in smart and responsive bio related nanotechnologies. She is the author/co-author of more than 150 manuscripts, reviews and book chapters. She is the recipient of many international prizes and honours including the L’Oreal UNESCO for Women in Science fellowship, the William Evans visiting fellowship from the University of Otago (New Zealand) and is a Visiting Scientist to the Bio-Nano Institute at Toyo University (Japan). Her research has been recently featured in “Where I work” published in Nature on the 20th May 2021.
Harald Sourij is Full Professor for Interdisciplinary Metabolic Medicine, the Head of the Interdisciplinary Metabolic Medicine Trials Unit, the Head of the Diabetes, Lipid and Metabolism Outpatient Clinics and Deputy Head of the Division of Endocrinology and Metabolism at the Medical University of Graz, Austria. After completing his studies sub auspiciis presidentis (summa cum laude) in 2004 and his training at the Medical University of Graz, Dr Sourij specialised as a consultant in internal medicine, as well as diabetes and endocrinology.
In 2010 Dr Sourij joined the Diabetes Trials Unit lead by Prof Rury Holman at the University of Oxford, UK, where he acted as the clinical lead for the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) until he returned to Graz, Austria in 2013. Since 2020 he is heading the Interdisciplinary Metabolic Medicine Trials Unit specialized in designing and executing mono- and multicenter clinical trials in the cardiometabolic field. Harald has published >185 manuscripts in peer reviewed journals including Lancet, European Heart Journal or Diabetes Care.
- 18:00 – 19:30 Guided City Tour of Old Town of Graz (start: Meeting venue, end: City hall)
- 19:30 – 21:30 Reception by the Mayor of the City of Graz (City Hall)
Friday, October 13, 2023
- 09:00 – 11:00 Scientific Session III: Modulation of NRF2 Chairs: Kattri-Liis Eskla, Estonia, and Ivana Stojanović, Serbia
Roberto Motterlini is Director of Research (DR1) at INSERM U955 within the Faculty of Health, University of Paris Est, France. He has a long-standing interest in the regulation, activity and biological significance of heme oxygenase-1 (HO-1), a ubiquitous defensive protein that degrades heme to carbon monoxide (CO) and biliverdin. His studies focused on the role of Nrf2 as a transcription factor in controlling HO-1 gene expression and uncovered the vasodilatory, anti-ischemic and anti-inflammatory properties of CO. His research led to the development of CO
releasing molecules (CO-RMs), small active compounds that deliver controlled amounts of CO in vivo and have been shown to exert important pharmacological actions to counteract vascular, inflammatory and metabolic disorders. Dr. Motterlini’s group has also characterized a new class of hybrid compounds, termed HYCOs, which have the ability to activate Nrf2 and simultaneously release CO. He is currently investigating whether CO and molecular O2 can compete for the same cellular targets to act as antagonists in the modulation of metabolic dysfunction and inflammatory conditions.
Roberta Foresti (PhD) is Professor of Biochemistry at the Faculty of Health at the University Paris Est Créteil and working as a scientist at the Mondor Institute of Biomedical Research (IMRB). Dr Foresti teaches different subjects, such as human nutrition, energetic metabolism and oxidative stress, to bachelor and master students. She has dedicated more than two decades to investigating the protective action of the heme oxygenase-1 (HO-1) pathway in the cardiovascular system and inflammation, additionally focusing on drug discovery approaches targeting Nrf2/HO-1. She contributed to demonstrate an important role for the HO-1-derived products bilirubin and carbon monoxide (CO) in the protection of cardiovascular function during stress and is currently interested in the study of CO in obesity and metabolism. Dr Foresti is responsible of International Relations at IMRB, organizing a series of activities for the international recognition of our institute, including a summer school on environmental aggressions and health/chronic disease.
Đorđe Miljković is a Research Professor and the Head of the Department of Immunology at the Institute for Biological Research “Siniša Stanković”, University of Belgrade. He studies cellular and molecular mechanisms involved in the pathogenesis of autoimmune diseases. His current main research interests are: role of gut immune cells in autoimmunity, mechanisms of autoimmunity progression/regulation, cell-based therapy of autoimmunity, modulation of autoimmune diseases by synthetic and natural compounds.
Mihaela Matovina is the Senior Research Associate in the Laboratory for Protein Biochemistry and Molecular Modeling at the Division of Organic Chemistry and Biochemistry of Ruđer Bošković Institute in Zagreb, Croatia, and Assistant Professor at Josip Juraj Strossmayer University of Osijek, Croatia. During her PhD, she has studied the molecular epidemiology of human papillomavirus and its involvement in cervical cancer progression and earned her PhD in the field of biology from the Science Faculty of the University of Zagreb in 2006. From 2006 to 2009 she worked as a Postdoctoral Associate at Brown University, Providence RI, USA where she worked in the laboratory of Prof. Arthur Landy on the mechanisms of site specific integration of lambda phage DNA in the bacterial chromosome. Currently, she is investigating pathophysiological role(s) of dipeptidyl peptidase 3 (DPP3). Her main focus are protein-protein interactions of DPP3, including its interaction with KEAP1 which is involved in the regulation of KEAP1-NRF2 pathway. She is also searching for novel interactors of DPP3 in order to gain more insight into its physiological role.
Neuroprotective role of Nrf2 activation in Parkinson´s disease
Noemí Esteras1,2 & Andrey Y Abramov1
1 Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, UK
2 Department of Biochemistry and Molecular Biology, School of Medicine, Complutense University of Madrid, Spain
Email: nesteras@ucm.es
Parkinson´s disease (PD) is one of the most prevalent neurodegenerative conditions, affecting more than 10 million people worldwide. About 10% of all patients present a genetical form of this movement disorder linked to autosomal dominant mutations in genes such as SNCA, PINK1, Parkin, LRRK2 or DJ-1. PD is characterized by the aberrant aggregation of alpha synuclein (α-SYN) protein and the loss of nigro-striatal dopaminergic neurons, responsible for fine movement control. Oxidative stress and mitochondrial dysfunction are well-known molecular hallmarks of PD and are believed to underlie the neurodegeneration process. Importantly, both have been previously shown to be targeted by pharmacological Nrf2 activation in other disorders.
Here, we have explored the ability of the potent Nrf2 activator omaveloxolone (omav) in recovering the mitochondrial function and antioxidant capacity in human in vitro models of Parkinson´s disease such as fibroblasts obtained from seven patients with the familiar form of the disease harbouring mutations in different genes (SNCA, PINK1, PARK2, DJ-1 and LRRK2). Our results show that omav is able to enhance the antioxidant defence of these cells by increasing glutathione levels both in basal conditio ns and when they are challenged with tert-butyl hydroperoxide, therefore protecting against oxidative stress. In addition, omav improved mitochondrial bioenergetic function as shown by the recovery of the mitochondrial membrane potential, which is typically reduced in the patient´s cells. We show that the underlying reason for this improvement is the role of omav in increasing mitochondrial NADH availability.
Our results show that Nrf2 activation is able to tackle two essential pathogenic pathways in PD: it enhances the antioxidant defence and promotes mitochondrial bioenergetics, opening new avenues for the potential neuroprotective role of omav in PD.
This research is sponsored by Reata Pharmaceuticals, Inc.
Noemí Esteras is currently a recent PI holding a Ramón y Cajal Fellowship at Complutense University of Madrid, Spain, where she first graduated in Pharmacy (2007) and obtained a PhD in Biochemistry and Molecular Biology (2012). She then developed most of her research career as a postdoc (from 2014) and Senior Research Fellow (from 2019) at the Queen Square Institute of Neurology, University College London, UK. Her work is focused in understanding the molecular mechanisms leading to neurodegeneration, and particularly, the interaction of mitochondria, oxidative stress and calcium signalling in the pathogenesis of disease. She is very interested in the role of Nrf2 as a modulator of mitochondrial function, both in brain physiology and as a therapeutic strategy in neurodegeneration, and has published several original and review articles on the topic.
- 10:40 – 11:00 Coffee Break | Poster Viewing
- 11:00 – 11:50 Keynote Lecture Chairs: Antonio Cuadrado, Spain, and Albena Dinkova-Kostova, UK
Masayuki Yamamoto graduated from Tohoku University School of Medicine in 1979 and Graduate School of Medicine in 1983. From 1983 to 1986, he worked as a postdoctoral fellow at Northwestern University under the guidance of Professor Engel. Collaboratively, they identified the GATA family of transcription factors, now widely recognized as a foundational transcription factor family that regulates lineage commitment and cellular differentiation. In 1995, Yamamoto initiated an in depth analysis of the CNC-sMAF family of transcription factors. He had identified and established the KEAP1-NRF2 system, which controls the cellular response to electrophilic and oxidative stresses. His research in this domain continues to break ground. Throughout his career, Yamamoto has been honored with awards, such as: Leading Edge in Basic Science Award (SOT, 2011), Medal of Honor with Purple Ribbon (The Emperor of Japan, 2012), Japan Academy Prize (2014), Award for Research Excellence (FAOBMB, 2020), Lester Packer Award (2021). In a move to assist in the reconstruction efforts following the devastation of the Great East Japan Earthquake, Yamamoto founded the Tohoku Medical Megabank organization in 2012 and currently serving as an Executive Director.
- 11:50 – 13:10 Scientific Session IV: Modulation of NRF2 Chair: Santiago Cuevas Gonzalez, Spain, and Marlene Santos, Portugal
Chakradhara Rao S Uppugunduri holds a PhD in Medical Pharmacology. He is currently working at CANSEARCH Research platform of pediatric oncology and hematology of University of Geneva and heading the experimental research at this platform. He is a recognized Clinical Pharmacologist from Swiss Society of Clinical Pharmacology and Toxicology (SSCPT). His research is focused on pharmacogenetics and personalized medicine with particular contributions in elucidating drug responses, drug-drug interactions in relation to genetic variants.
Gerasimos (Gerry) Sykiotis is Senior Staff Physician at Lausanne University Hospital and Associate Professor at the University of Lausanne. He specializes in clinical and basic endocrinology with a particular focus on thyroid physiology and thyroid diseases, including thyroid cancer. Since 2015, he is responsible for the thyroid clinic at the Endocrine Division of Lausanne University Hospital. His basic research, funded primarily by the Swiss National Science Foundation, focuses on the roles of cellular antioxidant response systems in thyroid physiology and pathophysiology. His clinical research focuses on the needs of patients with benign and malignant thyroid diseases.
Iveta Bernatova is a senior scientist, head of the Department of Experimental Hypertension at the Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia. She studied Biochemistry (1991), holds Ph.D. from Chemistry (1997) and a title Doctor of Sciences (D.Sc.) in the field of Animal Physiology (2009). Her research is focused on the regulatory mechanisms of blood pressure in various experimental models of hypertension and the ways of prevention and treatment of high blood pressure with special attention paid to the role of nitric oxide and oxidative stress in regulation of blood pressure and vascular functions. Significant part of her research is focused on the vascular effects of various natural substances in prevention and treatment of hypertension. The most recent studies are focused on the research of the role of NRF2- activator dimethyl fumarate (DMF) in the cardiovascular system. She is the author of ~120 peer-reviewed publications in extenso with more than 2000 citations.
Dilara Akcora Yildiz is an Assistant Professor at Biology Department, Mehmet Akif Ersoy
University. She graduated from the Biology Department, Faculty of Science, Ege University, Turkey in 2004. She received her master’s degree from the Medical Biology Department, Faculty of Medicine, Ankara University, Turkey in 2007 and studied the effect of T315I, E255K and M351T mutations in imatinib resistance in chronic myeloid leukaemia patients. In the same year she was awarded with a Postgraduate Education Scholarship in Australia by the Ministry of National Education of Turkey (MEB) (2008-2012). She then earned her Ph.D. degree in intestinal stem cell biology at Department of Pathology at The University of Melbourne in 2012. During her doctoral studies, she characterized the role of colony stimulating factor 1 receptor-ligand pair (Cfms/CSF1) and granulocyte macrophage colony stimulating factor (GM-CSF) in intestinal biology. She was the principal investigator of a research projects which were supported by The Scientific And Technological Research Council Of Turkey (TUBITAK). She is currently working as an investigator in other projects focused on multiple myeloma biology, brain tumors, cancer stem cells and antibody production. Dr. Akcora Yildiz was a participant at 9th HOPE Meeting with Nobel Laureates in 2017.
- 13:10 – 14:10 Lunch | Poster Viewing | Group Photo
- 14:10 – 16:10 Scientific Session V: NRF2 from Pathomechanisms to Therapeutics Chairs: Nesrin Kartal Ozer, Turkey, and Theo Zacharis, Greece
Antonio Cuadrado is a full professor of Biochemistry and Molecular Biology at the Department of Biochemistry, Medical School, Autonomous University of Madrid. He obtained his PhD degree in Biology in 1985 and enjoyed several postdoctoral stays in the National Cancer Institute-NIH with the help of Fulbright and Fogarty fellowships. He established his independent laboratory as Professor of Biochemistry in 1997 with a main interest on the study of molecular mechanisms involved in initiation and progression of chronic diseases. For the past years his main lane of research has been the validation of transcription factor NRF2, master regulator of cellular homeostasis as a new therapeutic target in chronic diseases with particular emphasis in neurodegenerative diseases (Alzheimer and Parkinson) and in fatty liver diseases. His current interest is the development of new NRF2-modulating drugs. Dr. Cuadrado has published over 160 primary and review articles, of which more than 80 are related to the role of NRF2 in physiological and pathological responses to disease.
Brigitta Buttari is a Researcher at Istituto Superiore di Sanità (ISS- Italian National Institute of Health), Italy. She was awarded Specialty in Applied Biotechnology in 2003 and PhD in Medical Microbiology and Immunology in 2008. Her main research interest is the study of cellular and molecular mechanisms involved in initiation and progression of inflammatory chronic diseases. A special research interest include the investigation of the natural compounds as modulators of oxidative stress and cellular processes to prevent cell damage and to suppress inflammation through modulation of the Keap1-NRF2 signaling pathway.
Harry van Goor is a fundamental researcher and a translational scientist who completed a PhD program at the University of Groningen and a post-doctoral fellowship at the Penn State University, Hershey, PA, USA. He is currently involved in various projects focusing mainly on the role of the reactive species interactome (ROS, NO and H2S) and NRF2 in COVID-19, aging, neurodegeneration, CV disease and the metabolic syndrome. His research group consists of MD/PhD students and PhD students from different nationalities and backgrounds. Harry van Goor has received several research grants from the Dutch Kidney Foundation. He was past President of the International society of Antioxidants, Nutrition and Health, Associate Editor of Renal Pharmacology and Management team member of the Cost Action on “Bench to bedside transition for pharmacological regulation of NRF2 in non-communicable diseases (BenBedPhar)” representing the Netherlands.
Fabio Di Domenico is Full professor of Biochemistry at Sapienza University of Rome. He obtained his PhD degree in Biochemistry in 2009. Before gaining his current position, he performed his research under the supervision of Prof. Butterfield at University of Kentucky, where he has been involved in the application of redox proteomics studies. His research is currently focused in understanding the mechanisms that associates increased redox imbalance, defective proteostasis and brain dys-metabolism in the development of Alzheimer-like dementia. Collected data from his laboratory postulate that aberrant proteostasis, observed in both Alzheimer and Down syndrome patients, is strictly associated with the increase of oxidative damage as result of compromised antioxidant response and faulty protein
degradative systems. Recently, his studies revealed that the chronic induction of the unfolded protein response and its aberrant relationship with Nrf2 response hold a prominent role in the development of dementia in the brain from Alzheimer and Down Syndrome patients.
Paulo Matafome holds a PhD in Biomedical Sciences since 2012 (Faculty of Medicine, University of Coimbra). He is a Professor in the Polytecnic University of Coimbra and a Integrated member of CIBB (research center of University of Coimbra). He has published 91 research articles and 4 book chapters (>2000 citation, h=25). He has supervised or co-supervised 12 Ph.D. students (4 concluded), 18 MSc students, and 21 BSc Students. He has participated in 19 Research Projects and is one of the co-coordinators of PAS GRAS (Horizon Europe). Paulo Matafome has collaborations with the Departments of Surgery and Endocrinology of the University Hospital Center of Coimbra, with Brazilian, Spanish and Portuguese groups in the field of metabolic programming, and with the Institute of Health Applied Nuclear Sciences, developing new state-of-the-art bioimaging biomarkers (human and animal PET and MRI) for metabolic diseases complications. He has studied the neuroendocrine mechanism controlling the gut-adipose tissue crosstalk. He has access to human blood and adipose tissue samples, animal models of diabetes (Goto-kakizaki colony) and his lab has developed methods to evaluate angiogenesis and adipose tissue blood flow ex vivo and in vivo. He has studied several new antioxidant molecules in diabetic models in order to prevent vascular decline in adipose tissue.
Marisa Antunes (Master’s in Biochemestry). Research fellow at Centro de Química
Estrural (CQE) of the Faculty of Sciences of the University of Lisbon. Marisa was a
biomedical laboratory scientist at the Germano de Sousa Group – Center for
Laboratory Medicine, and now she is a research fellow at the CQE. She is
developing the following projects as a researcher: (1) Microcalorimetry and
fluorescence nanothermometry in early detection of immune T cell exhaustion; and
a systematic review (2) Clinical trials assessing Nrf2/ARE pathway as a therapeutic
target.
- 16:10 – 16:30 Coffee Break | Poster Viewing
- 16:30 – 17:20 Guided Poster Sessions (parallel sessions, 3 min presentation and 2 min discussion) | Session A Chairs: Irina Milisav, Slovenia, and Isabel Lastres-Becker, Spain
Ana Sofia Falcão holds a PhD in Pharmacy since 2006 and she is currently working as a post doctoral researcher at the Molecular Mechanisms of Disease Lab, at Nova Medical School (NMS), from Universidade Nova de Lisboa. At NMS, she became interested in exploring innovative therapeutic approaches for neurodegenerative disorders or other age-related diseases, such as AMD. She is focused on in vitro systems to study retinal pigment epithelial cells that will be used for fundamental studies as well as for potential translational applications to treat retinal disorders.
NRF2 (Nuclear factor erythroid 2-related factor 2) is a transcription factor that plays an important role in cellular defence against oxidative stress and inflammation. NRF2 has also been implicated in various other pathologies, including neurodegenerative diseases, metabolic disorders, and cancer. TP53 is the most commonly mutated gene in multiple cancers including breast carcinoma and its targets could be upregulated by depletion of CHRNA5, a cholinergic receptor, or doxorubicin, a topoisomerase inhibitor used as an anticancer agent. However, the association between the TP53 status, CHRNA5 levels and/or doxorubicin and the expression of NRF2 target genes is largely unknown. Here, we performed RNA sequencing using MCF7 cells treated with siRNAs against CHRNA5, TP53 or both as well as wildtype TP53 over-expressing and isogenic heterozygous mutant TP53 expressing MCF7 cells. We obtained the NRF2 target lists from different online sources and generated heatmaps and treatment -gene bipartite co expression networks to identify the NRF2 targets influenced by TP53 expression or mutation status in the presence or depletion of CHRNA5. Interestingly we observed that HMOX1, a known mutant TP53 repressed target, was upregulated significantly in mutant cell lines when treated with the siCHRNA5. Moreover, we tested whether addition of doxorubicin, another TP53 inducer, modulated further the targets specific to NRF2. For example, TXN was upregulated in wildtype TP53 over-expressing siCHRNA5 treated cells but downregulated when doxorubicin was present together with the siCHRNA5. Our pipeline can be applied to other datasets consisting of combinatorial treatments to better understand the mechanisms governing genotypic and drug induced variability in NRF2 signalling in different cancers. This study has been funded by a research grant from TUBITAK (Project no. 219Z029).
Monika Mlinarić is a PhD student working in the Laboratory for Oxidative Stress, Division of Molecular Medicine at Ruđer Bošković Institute. Under the guidance of Dr. Ana Čipak Gašparović, her research focuses on “Elucidating the role of aquaporins 3 and 5 in the development of breast cancer resistance to oxidative stress (AquaBCaRe).” Her PhD investigation involves studying the interaction between NRF2 and aquaporins, as well as their response to chronic oxidative stress conditions.
Ivan Koprivica is a Research Associate at the Department of Immunology, Institute for Biological Research “Siniša Stanković” – National Institute of the Republic of Serbia, University of Belgrade, Serbia, where he has been a part of the Diabetology Research Laboratory since 2016. His main research interest is focused on identifying cellular and molecular mechanisms responsible for Type 1 Diabetes (T1D) development in mice, as well as pharmacological modulation of experimental T1D, using a range of bioactive compounds in order to treat T1D autoimmunity. Recently, his research interests have also included investigating the role of gut immune cells in T1D development, as well as exploring the immunomodulatory potential of several novel synthesized AhR ligands.
Susana G Martins: I am a PhD Student at the Development and Evolutionary Morphogenesis Laboratory at cE3c (Faculty of Sciences, Lisbon University) under the supervision of Drs. Ana Rita Carlos and Sólveig Thorsteinsdóttir, with a MSc in Molecular Genetics and Biomedicine from FCT/UNL. The project I have been working on contributed to 2 oral presentations (one awarded with the prize for best short talk) and 12 posters presented in national and international meetings. Additionally, I actively contributed to the writing of two review articles, “Linking Oxidative Stress and DNA Damage to Changes in the Expression of Extracellular Matrix Components” and “NFIXing Cancer: The Role of NFIX in Oxidative Stress Response and Cell Fate”. I am also directly involved in mentoring master and undergraduate students and, last year, I was one of the winners of the Participatory Budget of cE3c. Recently, I received a grant for a Short-Term Scientific Mission within BenBedPhar Cost Action.
Biljana Miova is Full professor at the Institute of Biology, Faculty of Natural Sciences and Mathematics, “Ss Cyril and Methodius” University, Skopje, R. North Macedonia. The main interest of her scientific work is Experimental diabetes (treatments with plant extracts or some drugs, exploring the potential utilization in vitro plant cultures for treatment of experimental diabetes); Oxidative stress; Carbohydrate metabolism (key enzymes and substrates); Heat shock proteins, signaling molecules of apoptosis and cell death; High environmental temperature (acute and chronic heat stress, heat preconditioning and cross tolerance). She works with laboratory rats and animal cell cultures.
Tamara Saksida is a Principal Research Fellow at the Department of Immunology at the Institute for Biological Research “Siniša Stanković”, University of Belgrade. Her research interest are pathogenesis and modulation of autoimmune and inflammatory disorders with a focus on connection between gut immune system and distant sites, like pancreas in diabetes or the brain in Alzheimer’s & Parkinson’s disease.
- 16:30 – 17:20 Guided Poster Session | Session B Chairs: Sermin Genc, Turkey, and Christina Morgenstern, Austria
Sumesh Sasidharan is Senior Research Engineer at University College Dublin.His primary area of research is the development and application of insilico models in the treatment strategy of various cardiovascular pathological conditions like aneurysms and valvular heart diseases. He is recepient of international awards namely Civis3i Laureate (2023), Marie Curie Individual Fellowship (21-23), Australia Awards Endeavour Fellowship (2018), Elseiver Outstanding Reviewer (2018).
Minocycline attenuates the effects of H2O2 in subcutaneous connective tissue cells
Gülay Sezer
Department of Pharmacology, Faculty of Medicine, University of Erciyes, Kayseri, Turkey
Email: gulayszr@erciyes.edu.tr
Minocycline (Mino) is a tetracycline derivative antibiotic used in clinical practice mainly for the treatment of infectious diseases. Studies have shown that minocycline exerts neuroprotective and anti-inflammatory effects and combats oxidative stress. In this study, Mino-induced protective effects against hydrogen peroxide (H2O2)- induced cell damage and the involvement of nuclear factor erythroid 2-related factor 2 (Nrf2) was investigated. To examine the protective effect of Mino on H2O2-induced cytotoxicity, L929 mouse subcutaneous connective tissue cells were treated with Mino 1 h prior to H2O2 treatment. After incubation with H2O2 for 30 min, medium was decanted and cells were continued to incubation with Mino for 24 h and then MTT cell viability assay was performed. Wound healing assay was performed to investigate whether Mino has any effect on wound closure delay with H2O2. Effect of Mino on H2O2 induced apoptosis was determined by Annexin V labelling. The effect of Mino on H2O2-induced intracellular ROS generation was examined using DCFH-DA assay. qRT-PCR was performed to investigate the expression of Nrf2, Heme oxygenase (Hmox)-1, NAD(P)H quinone dehydrogenase 1 (Nqo1) and Collagen type Ia (Col1a) mRNAs.
Mino did not cause any significant changes in cell viability, but significantly reduced cytotoxicity induced by H2O2 treatment. Wound area was significantly reduced in the Mino-treated cells compared to the untreated control group. Mino pretreatment significantly reduced wound area compared to the H2O2-treated cells. The rate of apoptotic cells increased significantly in H2O2-treated cells, and Mino effectively reversed H2O2-induced apoptosis. ROS levels increased significantly in H2O2-treated cells compared with untreated cells and were significantly inhibited in the presence of Mino. Mino pretreatment significantly increased the mRNA expressions of Nrf2 and Hmox-1 compared to the control and H2O2 groups. Col1a mRNA expression was significantly decreased in the H2O2-treated group, and pretreatment of Mino was not effective in reversing, but Mino administration alone significantly increased the expression level compared to the control group.
The findings of this study suggest that Mino plays a protective role against the cytotoxic, wound closure delaying, apoptotic and oxidative effects of H2O2 probably by reducing ROS production and inducing Nrf2 and Hmox-1 mRNA expressions. Therefore, we propose the further development of minocycline as a cytoprotective and wound-healing agent.
Gülay Sezer Dr. Gülay Sezer is an Associate Professor at the Department of Pharmacology of the Faculty of Medicine at the Erciyes University (Turkey). After studying Pharmacy at Ankara Hacettepe University, she graduated from Erciyes University in 2002 with an MS degree. She received her doctorate degree from the same institution, Faculty of Medicine, Department of Pharmacology in 2007. During her doctorate, she had the opportunity to work in the Department of Pharmacology of the Polish Academy of Sciences in Krakow, Poland. She also teaches at the Genkok Genome and Stem Cell Center, Department of Molecular Biology and Genetics, Erciyes University. Currently, her interests focus on stem cells, cancer treatment and prevention of chemotherapy-related side effects.
Erkan Tuncay is an associate professor in Biophysics. He completed his MSc and PhD in the Department of Biophysics at Ankara University. His research is mainly focused on cardiac electrophysiology, particularly diabetic cardiomyopathy and heart failure. He has an interdisciplinary background with outstanding academic experience in various fields including physics, physiology, biology, imaging, medical device design, and biophysics. He had been at Imperial College London and New York University for his PostDoc studies. As a PI and co-investigator in national and international projects, he laid the groundwork for the proposed position by studying the effects of NAD+-dependent deacetylases, and intracellular ions on glucose homeostasis, protein trafficking, electrical and mechanical activity of the contractile cells in aging, insulin-resistant and diabetic animal models. With his active engagement in numerous national and international collaboration projects, he has earned distinguished international recognition for research excellence. He has published over 50 articles and holds 2 patents.
Kemal Yelekci graduated from Middle East Technical University, Chemistry Department. He was granted the Fulbright scholarship to pursue his Ph.D. degree in Ohio University in synthetic organic chemistry. He worked at Northwestern University (Chicago, USA) as a Post Doc. in medicinal chemistry and drug design and synthesis. Research and development involving studies of drug design and drug action, receptor ligand interaction and transporter protein mechanisms. In silico screening, calculation of free energy profile, elucidation of the flexibility and dynamical behavior of the protein-substrate complex are some of the major goals. Molecular docking methods to investigate the structure, kinetics and thermodynamics of biological molecules, especially enzyme-ligand complexes.
Dilruba Büşra ÇAKIR graduated with a bachelor’s degree in Genetics and Bioengineering in 2018. Currently, she is a master’s student at Karadeniz Technical University, Institute of Health Sciences, Department of Bioinformatics in Trabzon. Her research areas are based on bioinformatics, computer-aided drug design (CADD), and Next Generation Sequencing (NGS). A significant part of her studies has been focusing on the determination of protein structure & dynamics and understanding the molecular interaction between protein and protein or ligand through computational molecular modeling (in silico) methods.
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