Understanding the endosomal network in neurodegeneration

Professor Dario Alessi FRS, University of Dundee, UK

Dario is biochemist whose  research focuses on unravelling the roles of poorly characterised components which regulate protein phosphorylation or ubiquitylation pathways linked to human disease. He has contributed to our understanding of several disease relevant signal transduction pathways including PDK1 (diabetes and cancer), LKB1 (cancer), WNKs (blood pressure). Much of Dario’s current work is focused on understanding LRRK2 and how mutations in this enzyme cause Parkinson’s disease. In 1997 Dario became a program leader in the MRC Protein Phosphorylation and Ubiquitylation Unit, where he was appointed as its Director in 2012. He also serves as the Director of the Dundee Signal Transduction Therapy Unit, that  is a collaboration between scientists at the University of Dundee and pharmaceutical companies. Dario is passionate about the role that biochemical analysis can play in opening up our understanding of human health and disease. Dario Alessi’s publications have accumulated over 9,0000 citations (h-index 145). He has obtained several awards including the Francis Crick Medal and Lecture (2006) and election to the UK Royal Society (2008). Dario obtained a BSc (1988) and PhD (1991) from the University of Birmingham and carried out postdoctoral at the University of Dundee from (1991 to 1996).

Dr Natalie Connor-Robson, Dementia Research Institute, Cardiff University, UK

Having completed her PhD on the role of the synuclein family in health and disease with Prof Vladimir Buchman, Dr Connor-Robson joined the Oxford Parkinson’s Disease Centre in 2014 as a Career Development Fellow in the group of Prof Richard Wade-Martins. During this time, she worked on understanding the earliest cellular pathogenic events to occur in Parkinson’s Disease using both rodent and iPSC models. Her work highlighted the extensive roles of LRRK2 mutations in the endocytic and autophagic pathways as well as the role of GBA in Parkinson’s. In 2021, Dr Connor-Robson was awarded an Alzheimer’s Research UK Research Fellowship and joined the UK DRI at Cardiff as an Emerging Leader. Her research programme focuses on understanding the role of endocytic risk genes and polygenic risk in the development of Alzheimer’s disease.

Professor Darren Moore, Van Andel Research Institute, USA

Dr Darren Moore received an undergraduate degree from the University of East Anglia in 1998 and a PhD in molecular neuroscience from the University of Cambridge in 2001 in the laboratory of Dr Piers Emson. He conducted postdoctoral training with Professor Ted Dawson in the Department of Neurology and Morris K. Udall Parkinson’s Disease Research Center of Excellence at the Johns Hopkins University School of Medicine in Baltimore. Dr Moore joined the faculty at Johns Hopkins in 2005 as an instructor and became assistant professor in 2006. In 2008, Dr Moore moved to the Swiss Federal Institute of Technology (EPFL) in Lausanne as an assistant professor in the Brain Mind Institute. In 2014, Dr Moore joined the faculty at VAI as an associate professor in neurodegenerative science. He subsequently was promoted to professor in 2017 and to chair of the Department of Neurodegenerative Science in 2020. His laboratory is interested in understanding the biology and pathophysiology of gene products associated with inherited Parkinson’s disease.

Dr Kerri Kinghorn, University College London, UK

Dr Kerri Kinghorn is a Wellcome Trust Clinical Research Career Development Fellow at the Institute of Healthy Ageing, University College London (UCL) and an Honorary Consultant Neurologist at the National Hospital for Neurology and Neurosurgery. She completed the MB/PhD programme at the University of Cambridge and post-doctoral research at UCL as a Wellcome Clinical Fellow. This was followed by an Academic Clinical Lecturer post in neurology at Kings College London and a Rosetrees UCL Excellence Fellowship.  

Dr Kinghorn's research group seeks to understand the underlying pathogenic mechanisms of neurodegenerative disorders using the fruit fly Drosophila melanogaster, as well as cellular models of disease. Her research is focused on unravelling the underlying mechanisms linking genes involved in endosomal-lysosomal intracellular trafficking pathways and Parkinson’s disease. Her current works seeks to understand how endo-lysosomal autophagic defects in the gut and associated changes in its microbiome influence brain pathology via gut-brain axis communication. 

Dr Mark Cookson, NIA, NIH, USA

Dr Mark R Cookson is a cell biologist whose current research interests include the effects of mutations in the genes associated with neurodegeneration at the cellular and molecular level. His laboratory efforts are directed at finding the underlying pathways that lead to Parkinson's disease and related disorders. Dr Cookson received both his BSc and PhD degrees from the University of Salford, UK in 1991 and 1995, respectively. His postdoctoral studies included time spent at the Medical Research Council laboratories and at the University of Newcastle, UK. He joined the Mayo Clinic, Jacksonville, Florida, as an Assistant Professor in 2000 and moved to the NIA in February 2002. Within the Laboratory of Neurogenetics, Dr Cookson's group works on the effects of mutations associated with Parkinson's disease on protein function.

Professor Christine Klein, University of Lübeck, Germany

Dr. Christine Klein is a Professor of Neurology and Neurogenetics. She studied medicine in Hamburg, Heidelberg, Luebeck, London, and Oxford (UK) and did internships in Stockholm (Sweden), Rennes (France), Wollongong (Australia) and Vitebsk (Belarus). She moved to Boston from 1997-1999 for a fellowship in Molecular Neurogenetics with Dr. X.O. Breakefield and completed her neurology training at Luebeck University in 2004, followed by a series of summer sabbaticals in movement disorders with Dr. A.E. Lang in Toronto, Canada in 2004-2015. She was appointed Lichtenberg Professor at the Department of Neurology of Luebeck University in 2005, where her research has focused on the clinical and molecular genetics of movement disorders and its functional consequences. In 2009, Dr. Klein was appointed Schilling Professor of Clinical and Molecular Neurogenetics at the University of Luebeck and became Director of the newly founded Institute of Neurogenetics in 2013.

Dr. Klein has published >500 scientific papers and has an h-factor of 100 with >42,000 citations. She is Deputy Editor of ‘Movement Disorders’ and ‘Science Advances’ and former Associate Editor of ‘Annals of Neurology’ (until 2021), served as chair of the Congress Scientific Program Committee of the 2016/2017 Annual Congresses of the International Parkinson and Movement Disorder Society, is the acting Past-President of the German Neurological Society (~11,000 members) and Chair-elect of the European Section of the International Parkinson and Movement Disorder Society (MDS-ES). She has been elected a member of the National Academy of Sciences Leopoldina in 2021. Ten of her former doctoral students or mentees have been promoted to the level of assistant, associate, or full professor.

Professor Peter St George-Hyslop FRS, Cambridge Institute for Medical Research, UK and University of Toronto, Canada

Peter St George-Hyslop FRS is a medical scientist, neurologist and molecular geneticist who is distinguished for his research into neurodegenerative disorders, including Alzheimer’s disease (AD). In particular, he discovered several genes that when mutated lead to early onset hereditary AD, accelerating our understanding the disease and the development of potential treatments.

His discovery that defective genes encoding presenilins are a cause of familial AD led to presenilins becoming a new target for treatments. He went on to show that mutated presenilins contribute to the generation of the amyloid beta protein — deposition of which is the earliest sign of AD in those carrying such genes. His work on several other neurodegeneration-related genes and proteins (including SORLA, TREM2, FUS and ANXA11) has led to an understanding of the role of vesicular transport, inflammation and perturbed RNA granule biology.

Peter has led an AD research programme as Professor of Experimental Neuroscience at the University of Cambridge since 2007. He was awarded the Howard Hughes Medical Institute International Scholar Award in both 1997 and 2002, and has received several other notable awards.

Dr Henne Holstege, Clinical Genetics and Alzheimer Center Amsterdam UMC, The Netherlands

Henne Holstege is an Associate Professor at the Amsterdam University Medical Center. After she majored in biochemistry at the University of Leiden she did her PhD at the Netherlands Cancer Institute. During this time Dr Holstege was intrigued by the extraordinary case of a Dutch woman who died at age 115 without any symptoms of cognitive decline because this woman proved that cognitive decline is not inevitable. Holstege set up the 100-plus Study, a cohort study of cognitively healthy centenarians to identify protective genetic and biomolecular factors that associate with the escape of cognitive decline. She analyses the data from the centenarians in context of the genetics and biomolecular factors of (early onset) Alzheimer’s Disease; both extremes on the same cognitive spectrum. Therefore, her lab is involved in large international collaborative joint analysis of sequencing data thousands of Alzheimer Disease cases and cognitively healthy controls the collected by European ADES and American ADSP consortia. Holstege and collaborators are currently identifying novel genes associated with the increased or decreased risk of AD. Here, she applies specific focus on the identification of rare pathogenic variants in the SORL1 gene, which next to APOE-e4 allele, is the most common and strongest risk factor of AD. One of her major goals is, therefore, is to implement adequate clinical counselling strategies of SORL1 variant to the carriers and their family members. For this reason, a part of her lab is embedded in the clinic, and involved in counseling genetically predisposed Alzheimer Disease patients. For her work, Holstege was awarded the Alzheimer Research Prize by the Hans und Ilse Breuer Foundation in 2020. For more information see: www.holstegelab.eu.

Professor Peter Cullen, University of Bristol, UK

Biography not available

Professor Peter St George-Hyslop FRS, Cambridge Institute for Medical Research, UK and University of Toronto, Canada

Peter St George-Hyslop FRS is a medical scientist, neurologist and molecular geneticist who is distinguished for his research into neurodegenerative disorders, including Alzheimer’s disease (AD). In particular, he discovered several genes that when mutated lead to early onset hereditary AD, accelerating our understanding the disease and the development of potential treatments.

His discovery that defective genes encoding presenilins are a cause of familial AD led to presenilins becoming a new target for treatments. He went on to show that mutated presenilins contribute to the generation of the amyloid beta protein — deposition of which is the earliest sign of AD in those carrying such genes. His work on several other neurodegeneration-related genes and proteins (including SORLA, TREM2, FUS and ANXA11) has led to an understanding of the role of vesicular transport, inflammation and perturbed RNA granule biology.

Peter has led an AD research programme as Professor of Experimental Neuroscience at the University of Cambridge since 2007. He was awarded the Howard Hughes Medical Institute International Scholar Award in both 1997 and 2002, and has received several other notable awards.

Professor Scott Small, Columbia University, USA

Scott A. Small MD is the Director of the Alzheimer’s Disease Research Center at Columbia University, where he also directs the Psychosis Research Program.

Dr. Small focuses on disorders that affect the hippocampus, a brain structure targeted by Alzheimer’s disease, schizophrenia, and the normal wear & tear of the aging process. The hippocampus is a circuit comprised of a handful of microscopic regions. The overarching hypothesis motivating Dr. Small’s lab is that if hippocampal regions most vulnerable to a disorder can be pinpointed, this anatomical information can guide a search for the disorder’s root cause.

Accordingly, Dr. Small’s ‘anatomical biology’ lab has pioneered the development of MRI tools best suited to isolate vulnerable hippocampal regions. His lab has then used this information to identify mechanisms that are now thought to underlie Alzheimer’s disease, schizophrenia, and ‘cognitive aging’. Most recently, his lab has begun developing interventions for each condition. To date, the lab has completed two clinical trials for cognitive aging and one for schizophrenia, and the lab’s Alzheimer’s disease findings was the cornerstone around which a new biotechnology company, Retromer Therapeutics. was formed.