Frick Foundation for ALS Research
Frick Foundation for ALS Research
Group 1: Sandrine Da Cruz, Ludwig Cancer Research Institute, Univ. California San Diego USA. “Elucidating the contribution of oligogenic mutant gene synergy to ALS

dacruzDr. Da Cruz is Assistant Investigator of the laboratory of Neurobiology in the Ludwig Institute for Cancer Research at the University of California San Diego. She was trained with Professor Jean-Claude Martinou at the University of Geneva on fundamental aspects of mitochondria biology and established the first proteome of the mitochondrial inner membrane leading to the identification of several key mitochondrial components essential for cellular homeostasis. She then joined the laboratory of Professor Don Cleveland, recipient of the Breakthrough Prize in Life Sciences, to focus her postdoctoral efforts on mechanisms of neurodegeneration, initially to elucidate the contribution of mitochondrial damage to ALS pathogenesis. Her work demonstrated that loss of mitochondrial activity is critical for motor neuron cell death and muscle degeneration but not for distal motor neuronal degeneration and overall disease course, thus underscoring the importance of developing therapeutic strategies that counteract the initial muscle denervation and not uniquely focused on the subsequent motor neuron cell death.

As an independent investigator she is pursuing her long-standing interest in disease mechanism and therapy development for ALS and frontotemporal dementia (FTD), combining sophisticated mouse genetics and new in vitro human cellular models using neurons from ALS/FTD patient-induced pluripotent stem cells and muscle cells.

She received the Milton-Safenowitz Postdoctoral Fellowship from the Amyotrophic Lateral Sclerosis Association, the Fellowship for Advanced Researchers from the Swiss National Science Foundation and awards from the Muscular Dystrophy Association, the Robert Packard Center for ALS Research at Johns Hopkins, the Amyotrophic Lateral Sclerosis Association, and the Neurological Diseases and Stroke Institute of the NIH.

Group 2: Meredith Jackrel, Dept. Chemistry, Wash. Univ. St. Louis, USA. “Engineering Substrate-Optimized Hsp104 Disaggregases to Counter TDP-43, FUS, and DPR Protein Misfolding and Aberrant Phase Transitions in ALS”

jackrelMeredith Jackrel is an Assistant Professor in the Department of Chemistry at Washington University in St. Louis. She received her PhD in 2010 from Yale University where she studied protein – protein interactions and protein engineering. She then joined James Shorter’s laboratory in the Department of Biochemistry and Biophysics at the University of Pennsylvania as a postdoctoral fellow. There she developed techniques to re-engineer the protein disaggregase, Hsp104, to counter the misfolding of TDP-43 and FUS implicated in ALS. She has shown that these agents can directly solubilize TDP-43 and FUS aggregates and restore their proper localization. She was awarded a postdoctoral fellowship from the American Heart Association as well as a Target ALS Springboard Fellowship.

Currently Dr. Jackrel is working to test these agents against dipeptide repeat (DPR) protein accumulations implicated in C9orf72-ALS. The Jackrel Lab is also developing new approaches to engineer substrate-optimized variants that solubilize TDP-43, FUS, DPRs, and other proteins that aggregate in ALS. Additionally, the lab aims to define the effects that disaggregation of TDP-43, FUS, and DPR proteins have on aberrant phase transitions that underpin ALS. These disaggregases have therapeutic potential and can also be employed to further our understanding of the mechanisms of ALS.

Dr. Jackrel has also received a grant from the ALS Association.