Breaking the Wall of Lysosomal Brain Disease

Breaking the Wall of Lysosomal Brain Disease

Global Call 2026 Finalist Interview: Life Sciences

Monther Abu-Remaileh is an Assistant Professor of Chemical Engineering and Genetics at Stanford University. His lab uncovers how lysosomal metabolism enables adaptation to metabolic stress, revealing mechanisms in neurodegeneration and cancer while creating widely used tools to probe subcellular metabolism, and his work has been recognized with multiple major early-career awards.

Which wall does your research or project break?  

Our lab pioneers quantitative tools for high-resolution molecular analysis of cellular organelles, particularly lysosomes. Using LysoIP, they profile lysosomal metabolomes and proteomes in cells and living organisms—the first approach to directly chemically profile lysosomes in vivo, now widely adopted globally.

Key breakthroughs include: (1) Identifying glycerophosphodiesters (GPDs) as the primary toxic storage material in Batten disease (CLN3 deficiency), solving a decades-old mystery and establishing GPDs as clinical biomarkers; (2) Discovering CLN5 as the lysosomal BMP synthase, proving that lysosomes actively synthesize bioactive lipids; (3) Identifying PLA2G15 as the lysosomal BMP hydrolase and demonstrating that its inhibition rescues neurodegeneration; (4) Developing tagless LysoIP enabling lysosomal profiling from patient blood samples for biomarker discovery.

His work positions BMP metabolism as a central therapeutic target for Parkinson's and Alzheimer's.

What is the main goal of your research or project?  

The main goal of my research is to decode how lysosomes orchestrate cellular and organismal adaptation to metabolic stress and to translate this knowledge into new diagnostics and therapies for lysosomal and neurodegenerative diseases. My lab develops and applies quantitative organelle-isolation tools such as LysoIP and tagless LysoIP to profile the metabolomes, lipidomes and proteomes of lysosomes directly from cells, tissues and patient samples, allowing us to pinpoint which molecular changes are causal drivers of disease rather than downstream correlates.

A central objective is to build a mechanistic framework for BMP-centered lysosomal lipid metabolism—from synthesis to degradation—and to understand how tuning these pathways can restore cellular resilience in the brain and other tissues. Our work on Batten disease, where we identified glycerophosphodiesters as the primary toxic storage material, illustrates this strategy by linking a long-standing pathological hallmark to specific metabolites that can be tracked as clinical biomarkers. In parallel, defining CLN5 as the lysosomal BMP synthase and PLA2G15 as the BMP hydrolase shows that lysosomes actively generate and remodel bioactive lipids, opening therapeutic opportunities for Parkinson’s, Alzheimer’s and related conditions.

Ultimately, the goal is to connect lysosomal metabolism to clinical phenotypes in a way that enables rational drug design and early diagnosis. By integrating organelle-resolved omics with functional genetics, we aim to move the field from descriptive storage pathology toward targeted interventions that can prevent or reverse neurodegeneration and other consequences of lysosomal dysfunction.

What impact does your research or project have on society?

Lysosomal dysfunction underlies over 70 rare diseases and contributes to Alzheimer's and Parkinson's, collectively affecting tens of millions worldwide. Our lab's organelle-isolation tools are now used globally to identify disease mechanisms and drug targets. The discovery of the BMP synthase and hydrolase has directly enabled therapeutic programs for small-molecule BMP modulators. The tagless LysoIP enables biomarker discovery from patient blood samples, advancing clinical translation.

What advice would you give to young scientists or students interested in pursuing a career in research, or to your younger self starting in science?

The advice I would give to young scientists, and to my younger self, is to choose problems that genuinely matter to you and stay stubbornly curious about them, even when progress feels painfully slow. Research is not a straight path of successes but a long sequence of failed experiments, partial answers and unexpected detours; the people who make breakthroughs are usually those who keep showing up, refining their questions and learning from every setback rather than reading it as a verdict on their talent.