Frick Foundation for ALS Research
Frick Foundation for ALS Research
FRICK FOUNDATION FOR ALS RESEARCH
Drs. Kevin P. Kenna & James Mills

Drs. Kevin P. Kenna, Assistant Prof., Univ. Medical Center, Utrecht, NL & James Mills, Principal research fellow, Department of Clinical and Experimental Epilepsy, UCL, London, United Kingdom & Dept Neuropathology, Academic Medical Center, Amsterdam : Integrating genetics & neuropathology to identify causal RNA dysregulations in ALS

Dr Kevin Kenna is an assistant professor at the University Medical Centre Utrecht (Netherlands). He received his PhD from Trinity College Dublin (Ireland) in 2015, for analyses of rare genetic variation across genes, networks and biological pathways implicated in amyotrophic lateral sclerosis (ALS). He conducted his postdoctoral training at the University of Massachusetts Medical school, in the laboratory of Prof John Landers. During this time, Dr Kenna worked to develop methods for the integration and analysis of large exome sequencing datasets (>20,000 ALS patients/ healthy controls). Through rare variant analyses of >1,100 familial ALS exomes, Dr Kenna’s work led to the discovery of TUBA4A, NEK1 and KIF5A as novel ALS susceptibility genes. These findings were substantiated using additional exome, GWAS and genome sequencing datasets which revealed that patients can carry a range of higher frequency low impact risk variants (< 2 fold risk increase) as well as ultra rare high impact mutations that associate with specific clinical subtypes of ALS. The work also provided new insights into the contributions of cytoskeletal defects, neuronal transport, DNA damage and cilia function in ALS.

As a group leader, Dr Kenna continues to work on using genomic technologies to guide translational research and informative genetic testing in ALS. His group combines advanced computational techniques with genetic methods and multi-omic profiling of human post mortem tissue and stem cell models. In particular, Dr Kenna is focused on extending his work to the 98.5% of human genetic variants with effects in the non-coding genome. He does this in close collaboration with project MinE, the Dutch ALS centre and additional collaborators in Europe and the US.

Dr Kenna has received a vidi award from ZonMW, compute grants from NWO and additional funding awards from the Dutch ALS foundation (ALS Stichting).

Dr James Mills is a principal research fellow who holds a dual posting at the University College London (United Kingdom) and the Amsterdam University Medical Centre (Netherlands). He received his PhD in 2016 from the University of New South Wales (Australia) for his research that focused on the role of non-coding RNAs (previously classified as “junk” RNA) in the evolution of the brain in the context of neurodegenerative diseases. Here, his work led to the identification of the non-coding RNA, OLMALINC, as a key player in oligodendrocyte maturation in the human brain. On completion of his PhD he commenced a post-doctoral position at the Amsterdam University Medical Centre under the supervision of Prof Eleonora Aronica. Here, he worked on integrating different levels of transcriptomic data, with a specific focus on regulation of the protein-coding transcriptome by non-coding RNA. This led to the identification of several microRNAs (a class of non-coding RNA) as crucial regulators of important disease related pathways in epilepsy associated diseases.

In his current positions, Dr Mills leads computational biology teams that focus on utilising and integrating multi-omic approaches, including whole genome sequencing, transcriptomics, and DNA-methylation, to elucidate pathogenic mechanisms in complex diseases such amyotrophic lateral sclerosis, Parkinson’s disease and epilepsy. He continues to investigate regulation of the protein-coding transcriptome via non-coding RNA, as well as expanding his research lines to investigate structural variation in the human genome and gene expression changes at the level of a single cell.

Dr Mills has received grants from the Netherlands Parkinson Foundation (Stitching Parkinson’s fonds), the Top Sector for Knowledge and Innovation, and Amsterdam Neuroscience.

Dr Bradley Smith

Maurice Wohl Clinical Neuroscience Institute, Kings College London, Camberwell, London, UK. “Identifying ALS associated molecular and cellular changes in an Annexin A11 mutant knock-in mouse Model.”

Dr Smith is a Senior Research Fellow at the Maurice Wohl Clinical Neuroscience Institute in Camberwell, London. He obtained a PhD in 2007 studying the neurogenetics of ALS in the laboratory of Professor Chris Shaw. From 2010 as a Postdoctoral Researcher in Professor Shaw’s lab he led the UK arm of the Familial ALS Exome Sequencing Consortium and identified mutations in TUBA4A and most recently in the calcium and phospholipid binding gene Annexin A11. Dr Smith identified that one specific N-terminal Annexin A11 mutation, D40G was over-represented in familial cases, had a common founder and formed abundant, ubiquitous Annexin A11–positive protein aggregates in spinal cord motor neurons and hippocampal neuronal axons in post-mortem tissue from a D40G carrier. Since 2015, with Fellowship funding from the Medical Research Foundation (MRF), the Van Geest Foundation and grant funding from the Motor Neurone Disease Association (MNDA), he has been studying Annexin A11 specific disease mechanisms by developing and characterising Zebrafish over-expression and CRISPR-Cas9 models at Kings College. Dr Smith’s lab also continues to conduct novel ALS gene hunting studies in familial and sporadic Caucasian and Middle Eastern ALS populations. At present, Dr Smith is investigating a CRISPR-Cas9 mouse mutant knock-in model of Annexin A11 to assess conserved and translational disease mechanisms gained from Zebrafish studies. Furthermore, he is focussed on vesicle and organelle trafficking mediated by Annexin A11, identifying neuronal specific pathways associated with Annexin A11 and clarifying the role the protein plays at an endogenous level in RNA biology of motor neurons. An aim of this study will be identifying early cellular and molecular specific disease signatures associated with the replicated N-terminal Annexin A11 D40G mutation