In general terms, malfunctioning of epigenetic mechanisms regulating gene expression leads to diseases such as neoplastic transformation. Biomarker assays targeting disease related epigenetic changes can effectively be utilized as biomarkers at all stages of clinical disease management, from risk assessment, through early diagnosis and treatment personalization, to post treatment surveillance. Recently, large-scale clinical trials have shown that methylation biomarker-based cancer detection in liquid biopsies allows early detection of cancer in patients with remarkable specificity and sensitivity Specifically, detection of BRCA1 gene methylation in blood has been proposed as a biomarker of predisposition to breast and ovarian cancers. Additionally, methylation of the MGMT gene has long been used to guide treatment of glioblastoma multiforme patients. And recently, the genome wide profiling methylation has been suggested by the WHO as an alternative to standard histopathology for the classification of brain tumors. In my talk I will review recent developments in methylation biomarker research and applications of epigenetic biomarkers in clinical disease management.

Main Target Audience: Oncologists, Geneticists, Pathologists; Clinical Laboratories; Hospitals; - Researchers interested in the following topics: Cancer, Epigenetics, Biomarkers, Clinical Diagnostics, Cytogenetics, Pathology, DNA Regulation/Transcription, Genomics/Molecular Biology, Drug Discovery

Why should you attend?: Whether you are a scientist, a student, a lab technician, or a curious citizen, this webinar will provide fascinating insights into new tools to monitor epigenetic cancer biomarkers that will deepen our understanding of cancer emergence, pathology, diagnostics, and outcome.

Presented by: Prof. Dr. Tomasz K. Wojdacz
Associate Professor of personalized medicine
Department of Biomedicine, Aarhus University, Denmark and CEO & Co-Founder Methyldetect ApS

Topic: Epigenetics, Clinical

In vertebrates, a special secondary lymphatic organ, the spleen, is responsible for immunological survey of the blood. This task necessitates an astonishing solution for directly confronting T- and B-lymphocytes and macrophages with blood-borne materials: In humans and rodents, the arterial and the venous side of the splenic microcirculation are completely separated by a gap. This gap is filled by connective tissue of the splenic cords. Thus, blood leaves the open ends of the arterial capillary network, freely traverses the cords and then enters the venous sinuses from the outside via functional slits in their walls. On its way across the cords, the blood flows along the cell membranes of fibroblasts and of a large population of highly active macrophages without any barrier formed by endothelial cells. In humans, in addition to the sinuses, there is a second spleen-specific type of microvessel, the sheathed capillaries, which feed the capillary network.
We used Enzo chromogens in light microscopic triple staining of serial sections to definitively demonstrate that the arterial and the venous side of the human splenic microvasculature lack any connections. This was possible by detecting open capillary ends and by visualizing their unique morphology in 3D models viewed in virtual reality. Our method also permitted defining sheathed capillaries as post-arteriolar vessels surrounded by sheaths consisting of special stromal sheath cells, macrophages and recirculating B-lymphocytes. The sheaths most likely represent the splenic entry compartment for all types of antigens and particulate substances from the blood, because they are irrigated by open side branches of their capillary. Using 3D models based on immunohistology in transmitted light we are able to settle the 170-year-long debate of open versus closed circulation in the human spleen and provide previously unseen insight into the tissue microanatomy of the spleen.

Main Target Audience: Anatomists, Physiologists; Histologists; Clinical Laboratories; Hospitals; - Researchers interested in the following topics: Anatomy, The cardiovascular system, Immunohistochemistry (IHC), Histology, blood circulation, Immunology, Pathology

Why should you attend?: Whether you are a scientist, a student, a lab technician, or a curious citizen, this webinar will provide fascinating new anatomic insight into the architecture of the spleen and highlight captivating, state-of-the art digital visualization of immunohistochemistry results, a method which forms the pillar of our anatomical understanding since over a century.

Presented by: Prof. Dr. Birte Steiniger
Professor emeritus and head of Department of Immunobiology
Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Marburg

Prof. Dr. Oleg Lobachev
Professor for IT-Security and Artificial Intelligence
Leibniz University of Applied Sciences, Hannover

Topic: IHC, Immunology

B cells are responsible for the humoral immune response against pathogens. They mature with age in response to the environment, refining their antigen receptors. Their functions are extremely complex and go beyond the production of specific antibodies. Therefore, any glitch occurring in the sophisticated B cell machinery can lead to pathology, from immunodeficiency to autoimmunity. Understanding the different subpopulations of human B cells and their functions is key to unravel defects in B cells in patients with immunodeficiency and autoimmunity.
We investigated B cell functions in infancy and throughout childhood, through in vitro functional tests. We show that T-independent stimulation with CpG measures proliferation and the differentiation potential of memory B cells. Switched memory B cells respond better than IgM memory B cells. During childhood, the production of plasmablasts in response to CpG increases with age mirroring the development of memory B cells. On the other hand, CD40L, a T-dependent stimulus, does not induce plasma cell differentiation, but causes proliferation of naive and memory B cells. The response to CD40L does not change with age. Finally, in patients with selective IgA deficiency (SIgAD), we observed that switched memory B cells are reduced due to the absence of IgA memory B cells. In agreement, IgA plasma cells are not generated in response to CpG. Unexpectedly, B cells from SIgAD patients show a reduced proliferative response to CD40L. Summary: I will report our experience on the study of B cell functions in infancy and throughout childhood and show how the proliferative potential, plasmablast differentiation and immunoglobulin secretion of B cell subsets can be reliably assessed in children through T-independent activation by the TLR9 agonist CpG. We also demonstrate how B cells respond to T-dependent co-stimulation. Finally, we show that in vitro functional tests can support physicians in assessing the state of the humoral immune system of patients with immune defects.

Main Target Audience: Anyone interested in human B cell biology. Research scientists in the academic and clinical field, at any career stage.

Why should you attend?: A clear and detailed description of in vitro B cell responses to different stimuli is crucial in order to design standardized and reproducible functional tests. Dr Marasco will talk about his experience on the study of B cell functions in children and young adults, providing an example of how in vitro functional tests could be conducted and interpreted in everyday clinical practice.

Presented by: Dr Emiliano Marasco, MD
Physician-scientist
Division of Rheumatology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Topic: Immunology

ADolutegravir (DTG) is a first-line antiretroviral drug used in combination therapy for the treatment of human immunodeficiency virus type-1 (HIV-1) infection. Due to roll out of generic DTG-based regimen and rising pretreatment resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) in resource limited countries (RLCs), 15 million HIV-1 infected people will be treated with DTG by year 2025. This includes women of child-bearing age who remain a significant infected population. However, growing data have suggested that DTG is associated with birth defects and postnatal developmental neurologic abnormalities following periconceptional usage and thus, concerns have emerged for its usage in pregnant women or those of child-bearing age. To this end, uncovering an underlying mechanism for DTG-associated adverse fetal neurodevelopmental outcomes has gained clinical and basic research interest. We now report that DTG inhibits matrix metalloproteinases (MMPs) activities that could affect fetal neurodevelopment. DTG was found to be a broad-spectrum MMPs inhibitor. It was more potent MMPs inhibitor than doxycycline. DTG was found to bind Zn++ at the catalytic domain to inhibit MMPs activities. Moreover, inhibition of MMPs activity was found to be an integrase strand transfer inhibitor (INSTI) class effect. Studies performed in pregnant mice showed that DTG readily reaches to the fetal central nervous system (CNS) during gestation and inhibits MMPs activity during critical period of brain development. Further postnatal evaluation of brain health in mice pups identified neuroinflammation and neuronal damage following in utero DTG exposure. Thus, we conclude that DTG inhibition of MMPs activities during gestation has the potential to affect pre- and post-natal neurodevelopment.

Summary: With an increased coverage of antiretroviral therapy (ART) for pregnant and breastfeeding women worldwide, >1 million HIV-exposed uninfected (HEU) children are born every year. With recommended wide-spread use of DTG-based regimen worldwide during pregnancy and increased concerns about DTG-associated neurodevelopmental abnormalities, there is an urgent need to identify unknown adverse drug effects on CNS development and underlying mechanism. Prior works focused on determining relationships between folate levels or transport pathways and DTG-associated birth defects failed to conclusively generate any cause-effect relationships. To this end, we show, for the first time, that DTG inhibits activity of matrix metalloproteinases (MMPs) during critical period of fetal CNS development, which could affect postnatal neurologic outcomes.

Main Target Audience: Anyone studying neural development, neuroscience, metalloproteinases (MMPs), pharmacology, immunology, inflammation, or human immunodeficiency virus type 1 (HIV-1). Also has relevance to clinicians.

Why should you attend?: In this webinar, Dr. Bade will discuss a potential link between neurodevelopmental abnormalities and antiviral dolutegravir treatment in pregnant women. You will learn how a mechanism of metalloproteinase inhibition in the prenatal brain of mice may explain these abnormalities.

Presented by: Aditya N. Bade, PhD
Instructor
University of Nebraska Medical Center; Department of Pharmacology and Experimental Neuroscience

Topic: Neuroscience

Presented by: Dr. Gerard J. Nuovo
Professor of Pathology
Ohio State University Comprehensive Cancer Center

Topic: Clinical

Gut dysbiosis is increasingly associated with the pathogenesis of protein conformational diseases such as Parkinson’s and ALS. Therefore, understanding the microbial contribution to protein stability and disease is critical for developing more effective interventions. The Czyz lab employs C. elegans with Enzo’s PROTEOSTAT® AGGREGATION ASSAY kit to detect bacteria-induced changes in the protein folding environment resulting in aggregation and pathogenicity. Overall, the Czyz lab reveals that detrimental bacteria disrupt host proteostasis and contribute to disease pathogenesis in the C. elegans model.

Who should attend this webinar?
Anyone interested in neurological health and disease.

Why should you attend this webinar?
Whether you are a scientist, a student, or a curious citizen, this webinar will exemplify real world applications of cutting edge technology for the advancement of neuroscience and treatment of neurodegenerative diseases by identifying underlying causes of protein misfolding.

Presented by: Dr. Daniel Czyz
Assistant Professor
University of Florida

Topic: Neuroscience

Are you in the bioprocessing field?
If so, let Enzo help you navigate the daunting quality control aspects of your operation by providing 7 simple tools to maximize your bioprocess pipeline. Whether you work in drug discovery, upstream, or downstream bioprocessing, Enzo offers a range of products to help you optimize product integrity, monitor contamination, and maximize yield.

Who should attend this webinar?
Anyone in the bioprocessing field who wants to know more about characterizing their biologic, protein aggregation, formulation optimization, storage and packaging of their biologic, and how to monitor and detect contamination.

Why should you attend this webinar?
To ensure that you are optimizing your bioprocess pipeline to facilitate rigorous and reproducible quality control in order to produce the highest quality product while consistently and reliably scaling your operation.

Presented by: Heather Brown, PhD
Application Scientist
Enzo

Topic: Bioprocess