Frick Foundation for ALS Research
Frick Foundation for ALS Research
Group 1: Contribution of neuronal and muscular expression to the toxicity of FUS truncation Luc Dupuis & Clotilde Lagier-Tourenne

Luc DupuisLuc Dupuis is research director in INSERM (France). His research in conducted in Strasbourg in the INSERM unit called "central and peripheral mechanisms of neurodegeneration". He defended his PhD in 2003, was recruited as junior researcher in INSERM in 2005 and was recently promoted as research director (equivalent of full professor).His research is entirely focused on motor neuron diseases. He is using animal models of ALS to undercover the mechanisms of disease pathogenesis. To this aim, he creates novel models, based on genetic forms of ALS, and characterizes how these mutant genes can be toxic to motor neurons but also to other neuronal types, leading to the whole clinical picture. He is especially focusing on the causes of weight loss and hypermetabolism in patients and models. In 2013, he was awarded the young investigator award of the European network to cure ALS. He also participates since 2009 to the scientific advisory board of the French ALS association.

Clotilde Lagier-Tourenne M.D. Ph.D., University of California San Diego.

Clotilde Lagier-TourenneClotilde Lagier-Tourenne is Assistant Professor in the Department of Neurosciences and Assistant Investigator in the Ludwig Institute for Cancer Research at the University of California San Diego. She was trained as a Medical Geneticist with Pr. Jean-Louis Mandel and Pr. Michel Koenig in Strasbourg and with Pr. Michio Hirano at Columbia University where her research focused on the identification of new genetic causes of neurological disorders. During her postdoctoral training in the laboratory of Pr. Don Cleveland, she has explored the regulatory network between two ALS-related RNA binding proteins, TDP-43 and FUS/TLS, and their RNA targets. She has applied approaches in genomics to study the impact of TDP-43 and FUS/TLS on RNA splicing and gene regulation and demonstrated the broad role of these proteins in RNA processing.

Her recent efforts have characterized the accumulation of abnormal expanded RNAs transcribed from both directions in patients with a C9orf72 hexanucleotide expansion. With her colleagues, she has provided evidence supporting the therapeutic potential of Antisense Oligonucleotides (ASOs) in ALS and FTD linked to C9orf72 expansion. Her objectives as independent investigator are to develop patient-oriented research at the interface of her medical and postdoctoral training to understand the mechanisms of neurodegenerative diseases and develop therapeutic strategies.

She received the Alphonse Laveran Prize, the Milton-Safenowitz Postdoctoral Fellowship from the Amyotrophic Lateral Sclerosis Association and the Muscular Dystrophy Association Career development Award.

Group 2: Neuronal signaling as a therapeutic target for ALS.

Dr. Brian D. McCabe, Assistant Professor at Columbia University in New York, U.S.A

Brian Mc CabeDr. Brian D. McCabe is an Assistant Professor at Columbia University in New York, U.S.A. He is a graduate of Trinity College Dublin in Ireland, received his Ph.D. from the University of Cambridge in England and was a postdoctoral fellow at the University of California at Berkeley before moving to New York City.

The research of the McCabe group is directed towards understanding the motor system at two levels - the genetic network that regulates the development and function of motor synapses and circuits and the molecular mechanisms through which human motor neuron diseases disrupt motor function. In pursuit of both of these aims, they primarily investigate the motor circuits of the fruit fly Drosophila melanogaster. To isolate new synapse regulatory molecules, the McCabe lab has carried out forward genetic screens for mutants with disrupted neuromuscular junction synapse development. This approach has revealed novel trans-synaptic signaling pathways that regulate synaptic development in both Drosophila and mammals. To gain insight into motor neuron disease, they have used reverse genetics to generate mutant Drosophila strains designed to recapitulate the genetics of inherited human motor neuron diseases. Recently, they used this approach to demonstrate that the disruption of motor circuit activity is a major contributor to disease in a Drosophila model of Spinal Muscular Atrophy (SMA). Based on this finding pharmacological strategies designed to ameliorate motor circuit dysfunction are currently being evaluated in SMA patients. They also recently found that some ALS associated proteins, in particular FUS and TDP-43, work together in a common molecular genetic pathway. They are currently endeavoring to exploit this discovery to reveal the molecular mechanisms underlying ALS pathophysiology.