Biomolecules Webinar series | Recent Advances on Lysosomal Storage Disorders Pathogenesis: An Emerging Gaucher Disease Paradigm Shift

Lysosomal Storage Disorders, Gaucher Disease, Cell Signaling

Webinar Information

**Webinar Series on Biomolecules - an Open Access Journal**

Recent Advances on Lysosomal Storage Disorders Pathogenesis: An Emerging Gaucher Disease Paradigm Shift

Gaucher disease, as the most common lysosomal storage disorder, affects populations worldwide and places a huge economic burden on healthcare systems. Despite the advent of enzyme replacement therapies and the most recent substrate reduction therapy, many phenotypical aspects of the disease, including skeletal abnormalities and central nervous system impairment, cannot be fully treated and remain unsolved clinical issues.

Recent advances in basic research of Gaucher disease pathogenesis have challenged the classical paradigm of lysosomal storage and collected new evidence showing that the loss of glucocerebrosidase activity may affect several key cellular pathways (ER stress, autophagy, signaling transduction, inflammasome). These novel pathways require more extensive research efforts but offer an alternative window of therapeutic strategies.

In this webinar, we will summarize these discoveries and open a fruitful discussion on growing research areas that could pave the way for the development of alternative approaches for Gaucher disease.

This Webinar relates to the Special Issue Lysosomal Storage Disorders: Molecular Basis and Therapeutic Approaches.

Date & Time: 23 October 2020 03:00pm (CEST)

Chair: Dr. Enrico Moro

Speakers: Dr. Ricardo A. Feldman, Dr. Andrea Dardis

Webinar ID: 825 9187 3796

Webinar Secretariat: biomolecules.webinar@mdpi.com

This webinar will include the following experts:

Dr. Enrico Moro

Dr. Enrico Moro is an Associate Professor of Cell Biology at the Medical School of the University of Padova (Italy). He has authored 60 full-length publications in peer-reviewed journals, including several high-impact journals, such as Endocrine Reviews, Lancet, Developmental Cell, Cell Reports and PNAS. He was Coeditor of two Special Issues of the Journal of Endocrinological Investigation, and he is currently Guest Editor of a Special Issue on Lysosomal Disorders in Biomolecules. His research publications present a total impact factor of 336, mean impact factor of 5.6 and h-index of 27. His research has been funded by different entities (Italian Ministry of Health 2010–2013, Genzyme-Sanofi 2012–2017 and MPS society 2019–2021). Dr. Moro has been invited to speak at several international and national meetings. He is also a member of the Scientific Advisory Board for the International Society for Mannosidosis & Related Diseases (ISMRD). He has a strong background in human cell biology and mouse and zebrafish manipulation, and his current research focuses on the study of lysosomal storage disorders, particularly Gaucher disease and Hunter syndrome (mucopolysaccharidosis type II).

Department of Molecular Medicine, University of Padova, Padova, Italy.

Dr. Ricardo A. Feldman

Dr. Ricardo A. Feldman is an Associate Professor at the University of Maryland School of Medicine (UMSOM). Dr. Feldman received his PhD from the Department of Cell Biology at New York University School of Medicine, working with Drs. Takashi Morimoto and David D. Sabatini. After that, he was a post-doctoral fellow in Dr. Hidesaburo Hanafusa's laboratory at the Rockefeller University, where he identified several new tyrosine kinase oncogenes that had been captured by RNA tumor viruses, along with their cellular homologs. Dr. Feldman then moved to the lab of Dr. Doug Lowy at the National Cancer Institute (NCI, USA). He then joined the faculty of the UMSOM Department of Microbiology and Immunology, where he currently studies the developmental and cellular abnormalities caused by GBA1 mutations in Gaucher disease and GBA1-associated Parkinson’s disease. Using patient-derived induced pluripotent stem cells (iPSC), his laboratory identified the Wnt/B-catenin and mTORC1 pathways as critical targets of the sphingolipid imbalance caused by GCase deficiency. Dr. Feldman is a founding member of the Center for Stem Cell Biology and Regenerative Medicine at UMSOM.

Department of Microbiology and Immunology, University of Maryland School of Medicine (UMSOM), Baltimore, USA.

Dr. Andrea Dardis

Dr. Andrea Dardis is Head of the Laboratory of the Regional Coordinator Centre for Rare Diseases, Udine, Italy. She obtained her PhD in Molecular Biology from the University of Buenos Aires, Argentina, and continued her training as a post-doctoral fellow at the Metabolic Unit, University of California, San Francisco, USA. During her training, she was awarded Fellowship of the Lawson Wilkins Pediatric Endocrine Society. She then moved to Italy where she obtained a Specialist Degree in Medical Genetics at the University of Genoa. In 2003, she joined the Metabolic Diseases Unit, Pediatric Hospital “Burlo Garofolo”, Trieste, Italy, as a Research Scientist. In 2009, she moved to the Regional Coordinator Centre for Rare Diseases in Udine, Italy, where she became Head of the laboratory. Dr. Dardis’s laboratory is mainly focused on the biochemical and molecular diagnosis of lysosomal storage diseases, the functional characterization of defective lysosomal enzymes and the study of molecular mechanisms involved in the pathogenesis of lysosomal storage disorders. Dr. Dardis is a board member of the European Working Group on Gaucher Disease and a member of the board of trustees of the International Niemann Pick Disease Registry (INPDR).

Laboratory of the Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, Italy.

Webinar Program

The webinar will start at 3:00 pm (CEST) 23 October 2020 and will last a maximum of 2 hours.

Presentation	Time
Dr. Andrea Dardis "Cellular models for the study of the pathogenic cascade in Gaucher disease"	03:00 pm (CEST)
Q&A	03:20 pm (CEST)
Dr. Ricardo A. Feldman "GBA1 mutations cause neurodevelopmental defects and lysosomal dysfunction"	03:30 pm (CEST)
Q&A	03:50 pm (CEST)
Dr. Enrico Moro "Blowin’ in the Wnt: how glucocerebrosidase may shape a cell differentiation program"	04:00 pm (CEST)
Q&A	04:20 pm (CEST)
Discussion and Concluding Remarks	04:30 pm (CEST)

Webinar Content

The fourth Biomolecules webinar, entitled “Recent Advances on Lysosomal Storage Disorders Pathogenesis: An Emerging Gaucher Disease Paradigm Shift”, was held on Friday 23 October 2020. This online seminar included the scientific contribution of Dr. Andrea Dardis (Udine, Italy), Prof. Ricardo Feldman (Baltimore, USA) and Prof. Enrico Moro (Padova, Italy), and depicted the current view of Gaucher disease (GD) pathogenesis.

The use of inducible pluripotent stem cells (iPSCs), novel CRISPR-Cas9-based mutant cell lines and experimental models is giving a complex picture of the variety of pathogenic pathways implicated in the tissue-specific related GD abnormalities. The macrophage-centric paradigm of GD pathogenesis is being challenged by the growing idea of concurrent cellular defects occurring because of glucocerebrosidase loss of function. Abnormalities of the mTOR pathway, the canonical Wnt signaling cascade and the ER stress/mitochondrial axis emerge as key drivers in the onset of irreversible damages, which precede the glucosylceramide storage. In addition, there are still unexplored aspects of the disease (implication of epigenetic factors and modifier genes, and the contribution of mitochondrial–lysosomal and ER–endolysosomal defective tethering) that may deserve future investigations.

A shift in the paradigm of GD pathogenesis is taking shape, and it will certainly enable clinicians to better address the development of targeted therapeutic strategies that could prevent the onset of irreversible brain and bone impairments in affected patients.

The webinar was offered via Zoom, and registration was required for attendance. The full recording can be found below.

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Relevant Special Issues

Special Issues in Biomolecules

Lysosomal Storage Disorders: Molecular Basis and Therapeutic Approaches
Guest Editor: Dr. Enrico Moro
Deadline for manuscript submissions: 30 October 2020.