Gluck ALS Research Laboratory Group

Overview

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease characterized by a rapid loss of motor function, for which there are a limited number of disease-modifying treatments available. The multifactorial biology of the disease suggests that therapeutic strategies targeting a single biological pathway are unlikely to yield significant clinical benefit for the broad patient population. Establishing a multi-disciplinary platform to rigorously interrogate the biology of these different factors enables the identification of novel synergistic therapies that, when combined, may yield a therapeutic benefit far exceeding that of any individual intervention.

The Gluck ALS Research Laboratory Group serves as a collaborative nexus, bringing together five Principal Investigators and over 50 researchers to propel science and train the next generation of researchers. By centralizing the sharing of specialized knowledge, cutting-edge in vitro and in vivo models, and advanced screening capabilities, this platform creates a world class environment for identifying and validating the mechanisms of neurodegeneration and developing novel disease modifying therapeutics.

The group's leadership includes Drs. Mark Albers, Clotilde Lagier-Tourenne, Ghazaleh Sadri-Vakili, Yuyu Song and Brian Wainger.

Research Projects

Albers Lab

The Albers Laboratory integrates chemical biology and computational biology in human cellular and animal models as well as olfactory neurons from living patients to elucidate mechanisms of neurodegenerative diseases. The focus is on mechanisms that are detectable early in the course of disease. By utilizing advanced computational tools like TRIALS and DRIAD, the lab has identified synergistic drug targets and evaluates repurposed existing therapies in emulated clinical trials in the electronic health record and in the recently completed NADALS basket trial of ALS and Alzheimer’s patients. This multi-modal approach enables the discovery of precision therapeutics and companion biomarkers that bridge the gap between complex pathology and effective clinical intervention.

Lagier-Tourenne Lab

The Lagier-Tourenne Laboratory investigates the regulatory networks of RNA-binding proteins and RNA metabolism to uncover the molecular drivers of ALS and dementia. By integrating functional genomics across iPSC-derived neurons and animal models, the team elucidates how protein mislocalization and genetic expansions, such as C9ORF72, trigger the neurodegenerative cascade. These mechanistic insights are translated into clinical reality through collaborations with academic and industrial partners that have pioneered the development of RNA-targeting antisense oligonucleotides and immunotherapies for ALS and FTD.

Sadri-Vakili Lab

The Sadri-Vakili Laboratory investigates how transcriptomic instability and dysregulation of RNA processing contribute to the pathogenesis of ALS and related neurodegenerative disorders. The laboratory further examines the role of disrupted proteostasis in driving neuronal dysfunction and degeneration. Using high-resolution transcriptomic profiling integrated with cellular and in vivo disease models, the team identifies mechanistic pathways, candidate biomarkers, and therapeutic targets aimed at restoring immune homeostasis and preserving functional gene expression. This multidisciplinary approach enables the development of next-generation neuroprotective strategies to mitigate motor neuron degeneration in ALS.

Song Lab

The Song Laboratory integrates advanced imaging, structural biology, and multi-omics to explore the molecular mechanisms of selective neuronal vulnerability in ALS. By investigating the signaling pathways that connect protein misfolding, cytoskeletal disruption, and synaptic dysfunction, the team identifies the convergent drivers of ALS and related neurodegenerative diseases. These insights are leveraged to develop innovative therapeutic approaches that could restore neuronal structure and functional resilience.

Wainger Lab

The Wainger Lab utilizes iPSC-derived motor neurons, co-cultures, and mouse models to investigate the molecular mechanisms of ALS, with a primary focus on TDP-43 pathology and C9ORF72. By leveraging high-throughput screening and additive co-culture systems, the team interrogates motor neuron survival, neuromuscular junction integrity, and STING-mediated inflammatory pathways. This iPSC-derived discovery platform has successfully transitioned two repurposed FDA-approved therapies into the clinic: retigabine, which reduces pathological hyperexcitability, and digoxin, which was tested in the ACACIA Trial, a Phase 2a trial in Healey ALS MyMatch.

Collaborative Projects and Publications

Integrated Target Discovery Program 43 (iTDP43)
An important step in drug development is to demonstrate that the potential new therapy corrects pathological changes in different models of the disease. To date, validation studies have been conducted under varying conditions, with distinct outcomes, and different analysis methods. To improve this drug development pipeline, the laboratories of Drs. Clotilde Lagier-Tourenne, Mark Albers and Brian Wainger have come together to launch the integrated Target Discovery Program 43 (iTDP43). In this program, careful curation of multiple ALS disease models with clinically relevant endpoints forms a suite of assessments for new drugs that target TDP-43 mislocalization and pathology. This suite was developed in part by applying learnings from our own clinical trial experience.