Webinars

Home Meetings Webinars

Online NVF seminar series

Main organizer and chair: Prof. Amalia Dolga

 

Timetable and information about the webinars can be found here.

 

29th of June at 16:00-17:00 CET

Join Zoom Meeting
https://us02web.zoom.us/j/81636593063?pwd=qd2z864MeDqpH5YUsy5bf3VLAw63_x.
1

Meeting ID: 816 3659 3063
Passcode: 727286

Speaker: Prof. Dr. A.H. (Anke-Hilse) Maitland-van der Zee , Hoogleraar Precision Medicine in Respiratory, Amsterdam UMC

Title: Precision Medicine in Respiratory Diseases

Abstract: Chronic respiratory diseases are multifaceted diseases. They comprise multiple phenotypes, which might benefit from treatment with different types of targeted therapies. Refining these phenotypes and understanding their underlying biological structure would help to apply precision medicine approaches. Using different omics methods, such as (epi)genomics, transcriptomics, proteomics, metabolomics, microbiomics, and exposomics, allowed to view and investigate respiratory diseases from diverse angles. In this talk I will give some examples of precision medicine approaches that are (hopefully) close to
implementation in clinic.

 

 

 

13th of April at 16:00-17:00 CET

Speaker: Prof. dr. Laura Heitman, Professor of Molecular Pharmacology, Oncode Institute & Leiden Academic Centre for Drug Research (LACDR), Leiden University

Title: Targeting chemokine receptor CCR2 – From insurmountable antagonists to affinity-based probes.

Laura H. Heitman, PhD. is a full professor of Molecular Pharmacology at the Division of Drug Discovery and Safety at the Leiden Academic Centre for Drug Research (Leiden University), and at Oncode Institute. Her research interests are mainly focused on understanding and improving drug-receptor interactions, and more specifically, target binding kinetics and allosteric modulation of GPCRs and other membrane proteins, such as SLCs. She has obtained several competitive research grants, both personal and as part of consortia, all allowing her to study these novel, clinically relevant and highly translational concepts for drug action. Her research activities have currently led to an authorship on over 110 papers in this field, including one in Science (2012) and one in Nature (2016) with an H-index of 37. Lastly, she is the recipient of multiple awards (e.g. the ‘2017 MedChemComm Emerging Investigator’-award, runner up for the ‘2018 Prix
Galien Research’-award).

 

 

16th of March 2022 at 16:00-17:00 CET

 

Speaker 1: Prof. dr. R.H. (Rob) Henning, Professor of Pharmacology, Faculty of Medical Sciences, University of Groningen

Title: Hibernation inspired drug development.

Rob Henning explores the molecular mechanisms enabling the miracles of mammalian hibernation: a repetitive, rapid and reversible reduction of metabolism by over 90%, leading to a drop in body temperature close to freezing. Endogenous production of H2S takes center stage in protecting cells from damage during hibernation dictated swings in physiology. He will explain why hibernators inspired the team to search for allosteric modulators of cystathionine beta synthase (CBS) and how they approach the discovery of this new drug class.

 

 

Speaker 2: PhD candidate Mohammed Saleh, Leiden Academic Center for Drug Research

Mohammed Saleh is a PhD candidate at Leiden Academic Center for Drug Research, working under the supervision of Prof. Liesbeth de Lange and Dr. Jeroen Elassaiss-Schaap. The focus of his PhD research is to develop mathematical models to predict the pharmacokinetics of central nervous system in healthy and of diseased conditions. Mohammed studied pharmacy in Egypt and did his master’s in pharmaceutical sciences at Utrecht University. In between, he gained experience on the drug industry at Novartis.

 

Title: LeiCNS-PK3.0: a framework leveraging multiscale data for accurate brain PK predictions

Abstract: Assessment of the unbound drug concentration in the central nervous system (CNS) is crucial for drug development to evaluate efficacy of CNS drugs and the safety of non-CNS drugs. Measuring the unbound drug concentration in the CNS target sites, i.e. brain cells and the surrounding extracellular fluid (brain ECF), is limited by ethical restriction of the human brain sampling, while lumbar cerebrospinal fluid (CSF) has been shown to be an inaccurate surrogate of the drug concentrations in the brain. The Leiden CNS pharmacokinetic predictor (LeiCNS-PK3.0) is a physiologically based pharmacokinetic model that was previously demonstrated to adequately predict the CNS PK profiles. LeiCNS-PK3.0 accounts mechanistically for the CNS physiology, a feature that allows interpopulation and interspecies translations of the PK profiles. In this webinar, we will explore the LeiCNS-PK3.0 model development and application to predict the brain PK profiles in Alzheimer’s patients.

 

 

16th of February 2022 at 16:00-17:00 CET

Speaker 1: Dr. Amalia Dolga, Associate Professor in Regenerative Neuropharmacology at the University of Groningen

Upon appointment as a Rosalind Franklin Fellow at the Groningen Research Institute of Pharmacy, she established a molecular neurobiology unit within the molecular pharmacology department. Her laboratory aims at identifying the molecular mechanisms responsible for cell death and at elucidating their involvement in human diseases.

 

Abstract: Progressive neurodegenerative diseases, including Alzheimer’s or Parkinson’s disease afflict millions of people worldwide. To address this unmet clinical need, it is important to gain more insight into the molecular mechanisms that drive neurodegenerative disease pathology. As mitochondrial dysfunction and inflammation are responsible for the initiation and progression of the neuropathology, proteins that prevent deregulation of both pathways are considered as drug targets. During this talk, I will discuss about mitochondrial dysfunction in iPSC-derived neurons from Alzheimer’s disease, and metabolic reprogramming in mouse microglia and human iPSC-derived microglia.

 

 

 

Speaker 2: Dr. Cees Korstanje PhD, KorstanjePharma Consultancy, Scenic-Biotech B.V., LACDR RU Leiden.

Experienced Science Director in Pharma Development. Skilled in strategic programs to prepare for IND and POC, with hands-on experience in Pharmacology (in-vivo/vitro, model development, mode-of-action profiling, safety pharmacology, and PK/PD projects), Translational Science & Biomarkers, Clinical Pharmacology MOA/safety studies) in different therapeutic areas. Strong science and experience basis, with >25 IND’s and >5 Marketing Authorizations, Lead positions in collaborations with academic and CRO partners. Proven management and leadershipqualities. Graduated from Leiden University (Pharm D) and Amsterdam University (PhD), and worked at Utrecht University (Veterinary pharmacology) before entering the Pharma business. 70+ scientific publications. Visiting scientist at Leiden University, LACDR.

Pharmacology in a company setting: contributions to ‘go/no go’ for drug selectivity in a translational science context; to MOA, and Biomarkers.

Abstract: Pharmacologists fulfil essential roles in drug development projects, no matter if the drugs are biologics or chemical entities. In a company setting there is always multidisciplinary teamwork in the non-clinical, and clinical context. Activity of a potential drug is always considered in the context of its safety and ADME properties in humans as the ultimate goal. This presentation will give examples of projects with specific ‘context’ problems and how these problems were overcome to get a clear ‘go’ or ‘no go’ for the project.

 

19th of January 2022 at 16:00-17:00 CET

Antoinette Maassen van den Brink, Professor of Neurovascular Pharmacology, Internal Medicine, Erasmus MC

Professor Maassen van den Brink studied Biomedical Sciences in Leiden, and then obtained her PhD at the Department of Pharmacology at the (current) Erasmus MC, studying the coronary side effects of antimigraine drugs. She currently investigates the neurovascular aspects of migraine, with a special emphasis on the role of female sex steroids. She is also the head of the Junior Med School and PI of the Academic Centre of Excellence GESTURE (gender studies). She is a board member of the Dutch Headache Society, former board member of the Dutch Pharmacology Society and founding board member of the Dutch Society for Gender and Health. Further, she serves as a board member for the European Headache Federation and the Federation of European Pharmacological Societies.

Title: Neurovascular Pharmacology of Migraine

Abstract: Migraine is a neurovascular disorder, which is classified as the second disabler by the World Health Organisation.  While recently a lot of progress has been made in the treatment of migraine, still many aspects of migraine are not understood.  Calcitonin Gene-Related Peptide is one of the key players in the pathophysiology of migraine, but many aspects of its receptor pharmacology are still to be elucidated to enable the development of safer and more effective antimigraine medication in future.

 

Erwin L Roggen, Managing director at ToxGenSolutions

Dr Roggens obtained a degree in Biochemistry at the University of Antwerp in 1984. He has been involved for over 18 years in development, implementation, dissemination and acceptance of alternative methods to animal testing. His long-term vision is better human and environmental health and safety through the application of non-animal approaches for testing and assessment. In line with this vision, he established 3Rs Management and Consulting (3rsmc-aps.com), SenzaGen (senzagen.com) and ToxGenSolutions (toxgensolutions.eu), providing tools for driving promising non-animal tools from the bench to industry.

Title: Application of the Adverse Outcome Pathway (AOP) concept to understand the impact of environmental risk factors on the progression of age-related memory loss leading to Alzheimer’s Disease.

Abstract: While aging and genetics are important risk factors for acquiring sporadic Alzheimer’s disease (sAD), systemic and environmental factors are increasingly recognized to contribute to this risk in a still poorly understood way. Inspired by the tau-cascade hypothesis, a tau-driven AOP towards memory loss was constructed using existing (primarily) human data selected according to predefined selection/rejection criteria. Sequences of key events (KEs) and plausible key event relationships (KERs) triggered by the bidirectional relationship between brain cholesterol and glucose dysmetabolism were captured. To portray how environmental factors may contribute to sAD progression, information on chemicals and drugs, that experimentally or epidemiologically associate with the risk of sAD were mapped on this AOP. The result suggests that chemicals may accelerate sAD progression by plugging into 26 different sAD relevant molecular initiating events (MIEs). A complex network of aging-related homeostatic pathways that are sensitive to an accelerated deterioration in the presence of risk factors is implicated in the pathogenesis of e.g., sAD. Since sAD pathology and neurotoxicity share microRNAs (miRs) regulating common as well as overlapping pathological processes, literature was searched for miRs associated with human sAD and environmental neurotoxicity. Functional miR analysis using PathDip resulted in miR-target interaction networks linked to brain cholesterol and glucose dysmetabolism as well as KEs of the tau-driven AOP. While miR analysis confirmed most of the retrieved findings, 40 miRs were found to be involved in both sAD and neurotoxicity and to dysregulate key processes of the AOP. Creating miR-target interaction networks related to the pathological processes involved in early sAD progression, and environmental chemical-induced neurotoxicity, respectively, provided overlapping miR-target interaction networks. This overlap offers an opportunity to create an alternative picture of the mechanisms underlying early sAD progression. Looking at initiation and progression of sAD from this new angle may open for new biomarkers and novel drug targets for sAD before the appearance of the first clinical symptoms.

15th of December at 16:00-17:00 CET

Prof. Martina Schmidt, Department of Molecular Pharmacology, University of Groningen

Title: Pharmacological targeting of nanocompartments in COPD and Alzheimer’s disease.

Abstract: Chronic diseases afflict millions of people of our worldwide aging society causing individual suffering and an enormous economic burden on our health care system. Chronic obstructive pulmonary disease (COPD) and Alzheimer’s dementia are common chronic diseases threatening the world population. COPD and Alzheimer’s dementia show tissue degeneration, inflammation and oxidative stress. Environmental stressors such as air pollutants and smoke are traditionally linked to COPD. Recent research had shown that people living in highly polluted areas have a higher risk in developing Alzheimer’s dementia. Despite the global impact of COPD and Alzheimer’s dementia, there have been very limited breakthroughs in our understanding and insights into the underlying mechanisms into their causes, treatment or cure. Clustering of cyclic nucleotide (and calcium) signaling in defined subcellular compartments/microdomains (signalosomes) has developed as a promising route to pursue to shed light into the mechanism enabling cells to exert their highly specialized tasks. Drugs used to alleviate COPD and Alzheimer’s dementia symptoms are beta-agonists and phosphodiesterase (PDE) inhibitors. The molecular drug targets of these drugs – beta-adrenergic receptors and PDEs – are key players in compartmentalization. Our research team enrolled unconventional compartment players such as A-kinase anchoring proteins and exchange proteins directly activated by cAMP, and yet to be further characterized targets. We showed that endogenous signaling properties of these multi-protein complexes define drug action – processes being disturbed under disease conditions. To increase the probability to reprogram these multi-protein complexes and to subsequently restore their cellular function, we used approved drugs in combination with novel druggable components to achieve direct pharmacological targeting of nanocompartments. Our concept potentially not only holds for COPD and Alzheimer’s dementia but also for other chronic diseases.

I reach out to colleagues – both at university and company settings – to share knowledge, tools and compounds to develop novel compartmentalized treatment strategies.

 

Naďa Majerníková, PhD candidate, Department of Molecular Pharmacology, University of Groningen and UMCG

Supervisors: Prof Amalia Dolga and Prof. Wilfred den Dunnen

Title: Underlying mechanisms of ferroptosis in Alzheimer’s disease.

Abstract: Alzheimer’s disease (AD), the most common form of dementia, currently affects 40–50 million people worldwide. Despite the extensive research into amyloid β (Aβ) deposition and tau protein hyperphosphorylation (p-tau), an effective treatment to stop or slow down the progression of neurodegeneration is missing. Emerging evidence suggests that ferroptosis, an iron-dependent and lipid peroxidation-driven type of programmed cell death, contributes to neurodegeneration in AD. Therefore, how to intervene against ferroptosis in the context of AD has become one of the questions addressed by studies aiming to develop novel therapeutic strategies. However, the underlying molecular mechanism of ferroptosis in AD, when ferroptosis occurs in the disease course, and which ferroptosis-related genes are differentially expressed in AD remains to be established. Our objectives are to 1. analyze which ferroptosis-related genes are differentially expressed in AD brain dependent on cell type, disease progression and gender, and 2. to compare the expression of ferroptotic markers between a) white and grey matter, b) Aβ versus non Aβ areas containing areas and c) high p-tau versus low p-tau-related areas of human post-mortem brains. Future studies should focus on developing new tools able to demonstrate where and when cells undergo ferroptosis in AD brain and build more translatable AD models for identifying anti-ferroptotic agents able to slow down neurodegeneration.

 

Wednesday 10th of November, 17-18:00 o’clock

Prof. Anton Roks, Department Internal Medicine, Erasmus MC

Title: Modeling of vascular aging and drug target identification with DNA repair mutant mice.

Aging is the single largest cause of disease in economically advanced societies. Cardiovascular disease is strongly represented in this context. Non-atherosclerotic vascular aging is a growing topic, its implications in health and life span being increasingly appreciated. This used to be a problematic filed of research due to the lack of convenient methods. In recent years I have developed mouse models to explore this type of vascular aging, namely by partial inactivation of DNA repair in vascular cells. Persistent activation of DNA damage response leads to accelerated development of aging features independently from the presence of risk factors. In my presentation I will illustrate how this impacts cardiovascular function in comparison to the typical risk factor-induced problems.  Also, I will show how my lab has identified relevant drug targets using accelerated vascular aging mice.

Very recently I have developed an interest in redox regulation, and I am trying to develop this as a research line, again placing drug development center stage. My lab does not have all the required experience and facilities to examine important aspects of redox regulation, and I kindly invite anyone skilled for collaboration. Furthermore, we are collecting tissues continuously and I would be happy to share tissues with anyone who is interested.

 

7th of July, 17-18:00 o’clock

Prof Reinoud Gosens, Department of Molecular Pharmacology, University of Groningen

Title: Pharmacological targeting of tissue remodeling and repair in the respiratory tract.

My current research interests are focused on mechanisms that regulate structural remodelling and repair of the airways and lung parenchyma in asthma and COPD. Identifying novel therapeutics for chronic lung disease is my long-term scientific goal. In this endeavour, I focus my work on the one hand on asthmatic airway remodeling, and in particular on the regulation of this pathological process by cholinergic receptors and the airway cholinergic system. Using in vivo and in vitro models the aim is to unravel the muscarinic receptor subtypes and signaling involved. Moreover, we are interested in the mechanisms that regulate plasticity of the airway neural network in asthma for which we recently established stem cell-derived airway cholinergic neurons. A second focus of my work is regenerative pharmacology of the distal lung in COPD and IPF. Here, my research interests are mainly centered around the function and dysfunction of distal lung stem cells/progenitors in health and disease. In particular, I am interested in understanding progenitor cell-niche interactions in disease as a potential background for the discovery of novel drug targets. In my presentation, I will shortly discuss both research lines and invite collaboration in each of these areas.