DYRK1A, related kinases & human disease conference

Laurent Meijer, President of Perha Pharmaceuticals, initiated the DYRK1A conference. This Roscoff-based biotech company focuses on the research and development of protein kinase inhibitor molecules for the prevention of hearing loss and the treatment of cognitive deficits associated with trisomy 21 and Alzheimer's disease. For the 2021 edition of the conference, he has joined forces with Masatoshi HAGIWARA (Kyoto, Japan), and Peter P. DE DEYN (Antwerp, Belgium), specialists like him in the DYRK1A gene.

All major physiological phenomena are regulated by protein phosphorylation which is catalysed by protein kinases. Many diseases are associated with abnormal phosphorylation. Consequently, the last four decades have seen considerable efforts in the study of function and regulation of protein kinases in essentially all aspects of biology. In parallel, pharmacological inhibitors of kinases have become a major R&D area for the pharmaceutical industry in its search for new therapies. As of early 2020, 49 kinase inhibitors have reached the pharmaceutical market.

General presentation

DYRKs (‘dual specificity, tyrosine phosphorylation regulated kinase 1’) (DYRK1A, 1B, 2, 3, 4) play key roles in mRNA splicing, chromatin transcription, DNA damage repair, cell survival, cell cycle, differentiation, endocytosis, neuronal development and functions, synaptic plasticity, folate and methionine metabolism. Inhibition of DYRKs may find applications in Down syndrome, Alzheimer’s disease and tauopathies, Parkinson’s disease, CDKL5 Deficiency Disorder diabetes, osteoarthritis, viral infections and various cancers. The closely related CLKs (‘cdc2-like kinases) (CLK1, 2, 3, 4) also play essential functions in Alzheimer’s disease and tauopathies, alternative splicing, various viral infections, cancers, body temperature sensing. DYRK and CLK orthologs are found in plants, yeast and unicellular parasites.

The conference will focus on DYRK1A and related kinases, including structural, regulatory and functional aspects, substrates and interactors, functions at cell and organism levels as well as development and potential therapeutic use of selective pharmacological inhibitors.

Invited speakers (tentative titles)

• Mariona ARBONES, Barcelona, Spain
  • Control of neuron numbers by DYRK1A: lessons from mouse models
• Walter BECKER, Aachen, Germany
  • DYRK1B – a cancer drug target?
• Thierry BESSON, Rouen, France
  • Novel DYRKs/CLKs inhibitors
• Mara DIERSSEN, Barcelona, Spain
  • Clinical trials with EGCG, PERSEUS trial
• Peter DE DEYN, Antwerpen, Belgium
  • Down syndrome, Alzheimer’s disease & DYRK1A
• Susana DE LA LUNA, Barcelona, Spain
  • DYRK1A & DNA damage
• Masatoshi HAGIWARA, Kyoto, Japan
  • Development of inhibitors of CLK1 and DYRK1A, and their clinical applications
• Yann HERAULT, Strasbourg, France
  • The role of DYRK1A dosage in Down syndrome deficits
• Florian HEYD, Berlin, Germany
  • CLK in body temperature cycles
• Nathalie JANEL, Paris, France
  • DYRK1A interactants, a link between Down's syndrome and Alzheimer’s disease
• Stefan KNAPP, Frankfurt, Germany
  • Selective targeting of kinases regulation RNA splicing
• Akiko KOBAYASHI, Kyoto, Japan
  • Neuroprotection through suppression of inflammation by DYRK inhibitors
• Conrad KUNICK, Braunschweig, Germany
  • New DYRK1B inhibitors
• Laurent MEIJER, Roscoff, France
  • Leucettinibs, a second-generation family of DYRKs/CLKs inhibitors: from natural products to clinical applications
• Lenka MUNOZ, Sydney, Australia
  • Phosphoproteomic screen in cells upon DYRK1A inhibition: identification of new DYRK1A down-stream substrates
• William M. OLD, Boulder & Aurora, USA
  • Revealing new functions of DYRK1A through interactome and substrate profiling
• Sang Ki PARK, Pohang, Korea
  • Sequential phosphorylation of NDEL1 by the DYRK2-GSK3β complex is critical for neuronal morphogenesis
• Lucas PELKMANS, Zurich, Switzerland
  • Kinase-controlled phase transition of membrane-less organelles in mitosis
• Amélie PITON, Illkirch, France
  • DYRK1A, a gene frequently mutated in intellectual disability
• Randall J. ROPER, Indianapolis, USA
  • DYRK1A and skeletal deficits associated with Down syndrome
• Andrew F. STEWART, New York, USA
  • DYRK1A inhibitors for beta cell proliferation to treat diabetes

Program

The final program will be available in September 2021.

Abstract submission

Organization: Arial 11, 1 page maximum, title (bold), authors (underline presenting author), address, e-mail contact, abstract, 1-3 compact references, (funding). Save under ‘yourname.doc’ or ‘yourname.docx’.

Submit abstract as an attached Word document, through the Conference e-mail address (dyrk-conference@perha-pharma.com), with your name as ‘subject’.

Abstract submission deadline: August 31, 2021.

Instructions for speakers

There will be no poster sessions. We will try to have as many people as possible, especially students and post-docs, presenting their results. Besides invited speakers, submitted abstracts will be selected for long (15 min) or short (5 min) oral presentations (+ 5 min discussion).

Call for authors

We plan to put together an open-access e-book collating articles on the conference topic. It will be published by Frontiers in Neurology (www.frontiersin.org). Contribution to this e-book will be open to everyone, whether attending or not to the conference. The plan is to have the final e-book ready by the opening of the conference. Please consider this opportunity. More information will be sent to the DYRKs/CLKs community in the coming months.