Boston—The Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital (MGH) in partnership with ALS Finding a Cure (ALSFAC) selected four recipients for their inaugural global two-year ALS Scholars in Therapeutics program. The program received an outstanding pool of global applications from 6 countries. This year’s selected recipients are Juliet Goldsmith, PhD of University of Pennsylvania, Matthew Anthony White, PhD of Kings College London, Brian Jude Joseph, PhD of Harvard University and Su Min Lim, PhD of Massachusetts General Hospital, Harvard Medical School.
Juliet Goldsmith, PhD is recognized for her research in autophagic regulation of mitochondrial DNA in ALS with the guidance of her mentor Dr. Erika Holzbaur at the University of Pennsylvania. She earned her PhD in Biomedical Sciences at the University of California, San Francisco, where she studied the cellular recycling process called autophagy. She is currently investigating the essential role of autophagy to maintain neuronal homeostasis. In her initial postdoctoral research, she discovered that a normal function of autophagy in neurons is to clear mitochondrial fragments rich in mitochondrial DNA. She will be investigating whether perturbed autophagy in ALS leads to mitochondrial DNA accumulation, and thus contributes to inflammation associated with disease progression. She hopes that by understanding the fundamental biology, we can better identify therapeutic targets or early biomarkers for ALS.
Matthew Anthony White, PhD, is recognized for his research in targeting TDP-43 autoregulation for therapeutic benefit in ALS-FTD with guidance from his mentor Jemeen Sreedharan, PhD. He earned his PhD in Neuroscience from Cardiff University where he studied the role of the TNF superfamily in the development of the peripheral nervous system. He then began to focus on ALS at the Babraham Institute in Cambridge, where his studies focused on a new mouse model to understand why and how mutations in TDP-43 cause ALS. At the Maurice Wohl Clinical Neuroscience Institute, King’s College, London, he continued his TDP-43 research. Currently he has begun to use human pluripotent stem cells and CRISPR gene editing to create nerve cells with mutations in TDP-43 directly linked to human disease. His aim is to use these tools to identify small molecule drugs capable of altering TDP-43 in the central nervous system. By directly targeting this fundamental ALS and dementia protein, his hope is to discover new therapeutic routes that could benefit a wide range of patients.
Brian Jude Joseph, PhD, is recognized for his research into developing U1-inhibition as a treatment modality for SOD1 ALS with guidance from his mentor Kevin Eggan, PhD. He earned his PhD in Cancer Biology from Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences. He is deeply motivated to exploit the biology of nervous system disorders and advance novel therapies to address unmet clinical needs. In his focus of ALS, the underlying dysfunction is known to be genetically and/or molecularly connected to defects in RNA metabolism. He is utilizing his training to discover de novo transcript changes in ALS à la the recently reported truncated STMN2. In parallel, he is learning cell reprogramming and differentiation techniques to examine the potential of U1 inhibition for gene silencing in SOD1-mutant ALS patient cells. Using his research to advance biomarker discovery and develop gene silencing methods he hopes this will then yield improvements in the early detection and treatment of ALS.
Su Min Lim, PhD, is recognized for her research into a multiplexed image-based platform for therapeutic development in ALS with the guidance of her mentor Dr. Clotilde Lagier-Tourenne in the Department of Neurology at Massachusetts General Hospital, Harvard Medical School. She received her PhD in translational medical science at Hanyang University, Korea. Her research is focused on understanding the regulatory mechanism of RNA-binding proteins and RNA-protein aggregates and validating therapeutic targets through patient-specific cell models based on racial, genetic, and clinical characteristics. Her research project examines altered RNA metabolism and the aberrant aggregation of pathogenic RNA-binding proteins (RBPs) which have emerged as a central theme in ALS research. Despite tremendous progress in our understanding of the mechanisms underlying RBP alterations, it remains challenging to therapeutically target protein mislocalization and abnormal aggregation. For this project, she proposes to identify genes that modulate the abnormal accumulation of RBPs in ALS patient cells using a recently developed method called optical pooled CRISPR/Cas9 screen that combines high-content image profiling with in situ sequencing. Antisense oligonucleotides (ASOs) will then be used to validate the most promising targets with the goal of developing a new therapeutic approach for ALS patients. She also enjoys playing the violin for patients and their families.
The ALS Scholars in Therapeutics program provides funding for young investigators researching new treatments for people living with ALS. This two-year program is designed to engage clinician-scientists and post-doctoral fellows to gain training and experience in therapy development for ALS at their home institution with a unique optional industry experience in year two. All ALS scholars will be part of the broader Healey & AMG Center and ALS Finding a Cure’s global community. By engaging motivated and creative individuals with a passion for bringing treatments to people living with ALS, we are expanding the community of experts and expediting therapy development.
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