Online Discussion Club (ODC) by the Young-EuNet-INNOCHRON

July 6th, 2023 15:30 - 16:30 CEST

Topic: "Aberrant lipid metabolism in Shwachman-Diamond syndrome"

Presentation by: 

Dr Usua Oyarbide, PhD
Project Staff
Cancer Biology Department
Cleveland Clinic Foundation
Cleveland, Ohio, USA

Organizer: Valentino Bezzerri, PhD
Principal Investigator
Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata di Verona, Italy

Zoom link: https://us02web.zoom.us/j/7781623506

Related:

• Somatic genetic rescue of a germline ribosome assembly defect (Tan et al 2021) 

• Loss of Sbds in zebrafish leads to neutropenia and pancreas and liver atrophy (Oyarbide et al 2020)

Online Discussion Club (ODC) by the Young-EuNet-INNOCHRON

May 4th, 2023 15:00 - 16:30 CEST

Topic: "Immunological features of autoimmune disorders: a focus on acquired neutropenia"

Presentation by: 
Dr Elena Turrini
Pediatric Oncology and Hematology Unit,
University Hospital of Parma, Italy

Dr. Andrea Beccaria
G.Gaslini Children Research Hospital
Genova, Italy

Organizer: Valentino Bezzerri, PhD
Principal Investigator
Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata di Verona, Italy

Zoom link: https://us02web.zoom.us/j/7781623506

Related:

• Autoimmune Cytopenias and Dysregulated Immunophenotype Act as Warning Signs of Inborn Errors of Immunity: Results From a Prospective Study
• Common Variable Immunodeficiency and Autoimmune Diseases: A Retrospective Study of 95 Adult Patients in a Single Tertiary Care Center
• Autoimmunity as a continuum in primary immunodeficiency

Online Discussion Club (ODC) by the Young-EuNet-INNOCHRON

February 9th, 2023 15:00 - 16:30 CET

Topic: "Age-associated B cells in Aplastic anemia"

Presentation by: Dr Elena Solomou
Associate Professor
Internal Medicine-Hematology,Medical school
University of Patras, Greece

Organizer: Valentino Bezzerri, PhD
Principal Investigator
Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata di Verona, Italy

Download the presentation

Zoom link: https://us02web.zoom.us/j/7781623506

Related:

• Age‑associated B cells in autoimmune diseases
• Shared transcriptional profiles of atypical B cells suggest common drivers of expansion and function in malaria, HIV, and autoimmunity

Online Discussion Club (ODC) by the Young-EuNet-INNOCHRON

December 1st, 2022 15:00 - 16:30 CET

Topic: "Could altered neutrophil protease activity have a pathophysiological role in acquired neutropenia?"

Presentation by: Ms Angelika Mazur, PhD Student
Department of Immunology
Faculty of Biochemistry, Biophysics and Biotechnology
Jagiellonian University, Krakow, Poland

Organizer: Valentino Bezzerri, PhD
Principal Investigator
Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata di Verona, Italy

Zoom link: https://us02web.zoom.us/j/7781623506

Related:

• Armed for destruction: formation, function and trafficking of neutrophil granules. 
• Neutrophil granules and secretory vesicles in inflammation. 
• Serine proteases of the human immune system in health and disease.
• The Pathophysiological Role of Neutrophil Extracellular Traps in Inflammatory Diseases. 
• Neutrophil Extracellular Traps and Their Implications in Cardiovascular and Inflammatory Disease.  

Online Discussion Club (ODC) by the Young-EuNet-INNOCHRON

October 27th, 2022 15:00 - 16:30 CEST

Topic: "Impact of sex on circulating neutrophils in Chronic Obstructive Pulmonary Disease"

Presentation by: Dr. Barbara Mariotti,
Section of General Pathology
Department of Medicine
University of Verona, Italy

Organizer: Valentino Bezzerri, PhD
Principal Investigator
Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata di Verona, Italy

Zoom link: https://us02web.zoom.us/j/7781623506

Related:

• Impact of Sex on Circulating Leukocytes Composition in COPD Patients

• Sex differences in neutrophil biology modulate response to type I interferons and immunometabolism

Online Discussion Club (ODC) by the Young-EuNet-INNOCHRON

September 22nd, 2022 15:00 - 16:30 CEST

Topic: "Late Onset and Long Lasting Neutropenia in Children: A Cross-Sectional Study"

Presentation by: Dr. Charikleia Kelaidi
Department of Pediatric Hematology and Oncology,
"Aghia Sophia" Children's Hospital,
Athens, Greece.

Organizer: Valentino Bezzerri, PhD
Principal Investigator
Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata di Verona, Italy

Zoom link: https://us02web.zoom.us/j/7781623506

Related:

• Severe aplastic anaemia in children: Impact of histopathology profile and treatment on very long-term outcomes
• The paradigm of hematological malignant versus non‑malignant manifestations, driven by primary immunodefciencies: a complex interplay 

Online Discussion Club (ODC) by the Young-EuNet-INNOCHRON

June 23rd, 2022, 15:00 - 16:30 CEST

Topic: "Kinetics of the granulocyte compartments: fast or slow, that is the question"

Presentation by: Prof. Dr. Leo Koenderman,
Department of Respiratory Medicine and
Center for Translational Immunology
University Medical Centre Utrecht
Utrecht, The Netherlands

Organizer: Valentino Bezzerri, PhD
Principal Investigator
Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata di Verona, Italy

Zoom link: https://us02web.zoom.us/j/7781623506

Related:

• Kinetics of Neutrophil Subsets in Acute, Subacute, and Chronic Inflammation - PubMed (nih.gov)

• The journey of neutropoiesis: how complex landscapes in bone marrow guide continuous neutrophil lineage determination - PubMed (nih.gov)

• The Neutrophil Life Cycle - PubMed (nih.gov)

• What's your age again? Determination of human neutrophil half-lives revisited - PubMed (nih.gov)

Online Discussion Club (ODC) by the Young-EuNet-INNOCHRON

May 5th, 2022, 15:00 - 16:30 CEST

Topic: "A novel IL-10 –DEL-1 axis promotes granulopoiesis and sepsis survival in early life"

Presentation by: Dr Eleni Vergadi,
Assistant Professor of Pediatrics, School of Medicine,
University of Crete, Greece

Organizer: Valentino Bezzerri, PhD
Principal Investigator
Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata di Verona, Italy

Zoom link: https://us02web.zoom.us/j/7781623506

Related:

• Del-1, an Endogenous Leukocyte-Endothelial Adhesion Inhibitor, Limits Inflammatory Cell Recruitment
• A novel IL-10 – DEL-1 axis promotes granulopoiesis and sepsis survival in early life
• Secreted protein Del-1 regulates myelopoiesis in the hematopoietic stem cell niche

Online Discussion Club (ODC) by the Young-EuNet-INNOCHRON

March 24th, 2022, 15:00 - 16:30 CET

Topic: "Development of Translational Readthrough Inducing Drugs for Inherited Bone Marrow Failure Syndromes"

Presentation by: Elena Baldisseri, M.Sc.
Cystic Fibrosis Center,
Azienda Ospedaliera Universitaria Integrata di Verona, Italy

Organizer: Valentino Bezzerri, PhD
Principal Investigator
Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata di Verona, Italy

Zoom link: https://us02web.zoom.us/j/7781623506

Related:

• Strategies against Nonsense: Oxadiazoles as Translational Readthrough-Inducing Drugs (TRIDs)
• Stop codon context influences genomewide stimulation of termination codon readthrough by aminoglycosides
• Nonsense Suppression Therapy: New Hypothesis for the Treatment of Inherited Bone Marrow Failure Syndromes

Online Discussion Club (ODC) by the Young-EuNet-INNOCHRON

February 24th, 2022, 15:00 - 16:30 CET

Topic: "Karyotype instabity in Shwachman-Diamond Syndrome: lights and shadows"

Presentation by: Giovanni Micheloni, Ph.D
Centro di Medicina Genomica
Department of Medicine and Surgery
University of Insubria
Varese, Italy

Organizer: Valentino Bezzerri, PhD
Head of the preclinical Research Lab
Cystic Fibrosis Center, Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona

Zoom link: https://us02web.zoom.us/j/7781623506

Related:

• Shwachman-Diamond syndrome with clonal interstitial deletion of the long arm of chromosome 20 in bone marrow: haematological features, prognosis and genomic instability
• The frequent and clinically benign anomalies of chromosomes 7 and 20 in Shwachman-diamond syndrome may be subject to further clonal variations

Online Discussion Club (ODC) by the Young-EuNet-INNOCHRON

January 27th, 2022, 15:00 - 16:30 CET

Topic: "High-resolution structures of the human ribosome to decipher the molecular basis of snoRNAs dysfunction in disease"

Presentation by: Dr. Simone Pellegrino
Cambridge Institute for Medical Research,
Department of Haematology, University of Cambridge, 
Cambridge, UK

Organizer: Valentino Bezzerri, PhD
Head of the preclinical Research Lab
Cystic Fibrosis Center, Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona

Download the presentation

Zoom link: https://us02web.zoom.us/j/7781623506

Related:

• The role of OncoSnoRNAs and Ribosomal RNA 2’O-methylation in Cancer
• Regulation of translation by site-specific ribosomal RNA methylation
• Visualization of chemical modifications in the human 80S ribosome structure
• A Pan-cancer Analysis of the Expression and Clinical Relevance of Small Nucleolar RNAs in Human Cancer

Online Discussion Club (ODC) by the Young-EuNet-INNOCHRON

December 16th, 2021, 15:00 - 16:30 CET

Topic: "Non typical autoimmune and idiopathic neutropenia in pediatric age: new perspectives"

Presentation by: Dr. Andrea Beccaria
G.Gaslini Children Research Hospital
Genova, Italy

Organizer: Valentino Bezzerri, PhD
Head of the preclinical Research Lab
Cystic Fibrosis Center, Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona

Zoom link: https://us02web.zoom.us/j/7781623506

Related:

1. Autoimmunity as a continuum in primary immunodeficiency
2. Late-onset and long-lasting autoimmune neutropenia: an analysis from the Italian Neutropenia Registry

Download the presentation

Online Discussion Club (ODC) by the Young-EuNet-INNOCHRON

November 4th, 2021, 15:00 - 16:30 CET

Topic: "Immune dysregulation in COVID-19"

Presentation by: Dr. Eleni Gavriilaki
G Papanicolaou Hospital,
Thessaloniki, Greece

Organizer: Valentino Bezzerri, PhD
Head of the preclinical Research Lab
Cystic Fibrosis Center, Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona

Zoom link: https://us02web.zoom.us/j/7781623506

Related:

1. Endothelial Dysfunction in COVID-19 Lessons Learned from Coronaviruses
2. Genetic justification of severe COVID-19 using a rigorous algorithm
3. Severe COVID‐19 infection and thrombotic microangiopathy success does not come easily

Download the presentation

Online Discussion Club (ODC) by the Young-EuNet-INNOCHRON

October 7th, 2021, 15:00 - 16:30 CET

Topic: "The molecular basis of neutropenia in Israel- who should be referred to the NGS panel"

Presentation by:
Dr. Oded Gilad 
Department of Hematology-Oncology
Schneider Children’s Medical Center of Israel
Petach Tikva, Israel

Organizer: 
Valentino Bezzerri, PhD
Head of the preclinical Research Lab
Cystic Fibrosis Center, Azienda Ospedaliero Universitaria Ospedali, Riuniti, Ancona

Presentation summary

Online Discussion Club (ODC) by the Young-EuNet-INNOCHRON

July 22th, 2021, 15:00 - 16:30 CET

Topic: "Identification of causative variants in patients with genetically unclassified severe congenital neutropenia using iPSCs and CRISPR/Cas9 gene-editing"

Presentation by:
Dr. Maksim Klimiankou
Division of Translational Oncology
Department of Oncology, Hematology, Clinical Immunology and Rheumatology
University Hospital Tübingen, Germany

Organizer: 
Valentino Bezzerri, PhD
Head of the preclinical Research Lab
Cystic Fibrosis Center, Azienda Ospedaliero Universitaria Ospedali, Riuniti, Ancona

Online Discussion Club (ODC) by the Young-EuNet-INNOCHRON

June 24th, 2021, 15:00 - 16:30 CET

Topic: "Studying the immune deregulation in Chronic Idiopathic Neutropenia (CIN): Myeloid-Derived Suppressor Cells (MDSCs) and T regulatory cells (T-regs)"

Presentation by:
Nikoleta Bizymi, MD, MSc, PhDc,
Haemopoiesis Research Laboratory, Medical School, University of Crete, Heraklion, Crete, Greece

Invited Moderator: 
Panagiotis Verginis, PhD
Associate Professor of Biochemistry, Medical School, University of Crete
Affiliated Researcher in ΙΜΒΒ-FORTH

Organizer: 
Valentino Bezzerri, PhD
Head of the preclinical Research Lab
Cystic Fibrosis Center, Azienda Ospedaliero Universitaria Ospedali, Riuniti, Ancona

Summary

"Studying the immune deregulation in Chronic Idiopathic Neutropenia (CIN): Myeloid-Derived Suppressor Cells (MDSCs) and T regulatory cells (T-regs)"

Myeloid-Derived Suppressor Cells (MDSCs) are a heterogeneous population of immature immunoregulatory myeloid cells, which are elevated in various human diseases that involve chronic inflammation and tumor progression. They are divided in two subpopulations, HLA-DRlow/-CD11b+CD33+CD15+ (polymorphonuclear-PMN-MDSCs) and HLA-DRlow/-CD11b+CD33+CD14+ (monocytic-M-MDSCs). Through activation of the enzymes arginase 1 and nitric oxide synthase 2, and production of reactive oxygen species, they lead to suppression of T‑cell proliferation, inhibition of natural killer (NK) cell cytotoxicity, modulation of macrophage polarization and induction of development of regulatory T-cells (T-regs). T-regs suppress also the T-cell responses and are important for the immune homeostasis. (Bronte et al. Nat Commun 2016, Bruger et al. Cancer Immunol Immunother 2019, Bizymi et al. HemaSphere 2019)

Chronic Idiopathic Neutropenia (CIN) is the prolonged, otherwise unexplained reduction in the number of PMN below the lower limit of the normal range. The main pathogenetic mechanism for CIN implicates the increased, Fas-mediated apoptosis of the CD34+/CD33+ myeloid progenitor cells. Chronic inflammation driven by an inhibitory bone marrow (BM) microenvironment consisting of activated T-lymphocytes (oligoclonal profile) and pro-inflammatory mediators (TNF-α, TGF-b1, Fas-ligand, IFN-γ, IL-1b, and IL-6) is also involved. Data from our lab have shown that CD14++/CD16+ monocyte subpopulation is increased in patients, which can be associated with the enhanced antigen presentation and T-cells over-activation in the disease. (Bizymi et al. J Clin Immunol 2019)

Our study aims to explore, besides the pro-inflammatory factors, the possible involvement of these immuno-regulatory cell populations in the pathogenesis of CIN, through the investigation of their number and functional characteristics in CIN patients compared to healthy subjects.

Online Discussion Club (ODC) by the Young-EuNet-INNOCHRON

May 6th, 2021, 15:00- 16:30 CEST

Topic: "Lab-on-chip for studying Shwachman-Diamond Syndrome"

Presentation by: Nora Selicato, Research fellow,
Cystic Fibrosis Center of Verona, Azienda Ospedaliera Universitaria Integrata,Verona, Italy
CNR NANOTEC – Institute of Nanotechnology, Lecce, Italy

Invited Moderator: Dr Alessandro Polini,
Principal Investigator
CNR NANOTEC - Istituto di Nanotecnologia del CNR, Lecce, Italy

Organizer: Dr Valentino Bezzerri
Head of the preclinical Research Lab
Cystic Fibrosis Center, Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona

Summary

Lab-on-chip for studying Shwachman-Diamond syndrome mechanisms

Shwachman-Diamond syndrome (SDS) is a rare inherited multisystemic syndrome characterized by bone marrow failure, exocrine pancreatic insufficiency, skeletal dysplasia, failure to thrive, associated with juvenile myelodysplastic syndrome and high risk of leukemic transformation. 1 SDS is mainly caused by mutations in the Shwachman-Bodian-Diamond Syndrome (SBDS) gene (located on chromosome 7q11.22) encoding a protein involved in ribosomal biogenesis.2

There is no cure for SDS and the treatment is based on managing the symptoms.

One of the pathogenetic hallmark of the SDS patients is the impaired neutrophil and monocyte chemotaxis defect, that was previously studied with traditional cell migration assays, which cannot provide the temporal and spatial control of the chemical gradients, neither study the single cell behaviour. 3,4

In this project we would like to generate a lab-on-chip as a tool for a reduced scale chemotaxis assay, easy to use. It should represent a new research platform for in vitro drug screening in SDS primary cell lines.

Lab-on-chips are able to overcome the limitations of traditional chemotaxis assays due the advantage of visualization, precise control of the chemical gradient and small consumption of reagents.5

We fabricated a flow-free microfluidic prototype with three different perfusable compartments with distinct inlets and outlets, interconnected through a series of parallel microchannels that can be used to control cell migration on chip. The platform has been fabricated by multi-level photolithography and PDMS replica molding. Gradient profiles were previously evaluated to ensure an adequate time to perform the chemotaxis experiments and a preliminary cell line was used to set up the device for the purpose of this study.

The final aim of this project will be to evaluate a drug candidate potential in restoring the chemotaxis of SDS primary mononuclear cells (MNCs).

Bibliography

1. Shimamura A. Shwachman-Diamond Syndrome. Semin Hematol. 2006;43(3):178-188. doi:10.1053/j.seminhematol.2006.04.006
2. Bezzerri V, Cipolli M. Shwachman-Diamond Syndrome: Molecular Mechanisms and Current Perspectives. Mol Diagnosis Ther. 2019;23(2):281-290. doi:10.1007/s40291-018-0368-2
3. Orelio C, Kuijpers TW. Shwachman-diamond syndrome neutrophils have altered chemoattractant- Induced F-actin polymerization and polarization characteristics. Haematologica. 2009;94(3):409-413. doi:10.3324/haematol.13733
4. Dror Y, Ginzberg H, Dalal I, et al. Immune function in patients with Shwachman-Diamond syndrome. Br J Haematol. 2001;114(3):712-717. doi:10.1046/j.1365-2141.2001.02996.x
5. Zhao W, Zhao H, Li M, Huang C. Microfluidic devices for neutrophil chemotaxis studies. J Transl Med. 2020;18(1):1-19. doi:10.1186/s12967-020-02335-7