Integrative Science lab

Lysosomal membrane homeostasis and its importance in physiology and disease - Nature Reviews Molecular Cell Biology Lysosomes degrade cellular components, and their membrane is an important signalling hub. Recent insights into the mechanisms that maintain lysosomal membrane homeostasis — including the interplay bet...

Lysosomal membrane homeostasis and its importance in physiology and disease www.nature.com/articles/s41...

Systematic analysis of cellular cross-talk reveals a role for SEMA6D-TREM2 regulating microglial function in Alzheimer’s disease An analysis of cell-cell communication in Alzheimer’s disease reveals insights into disease biology and potential therapeutic targets.

Systematic analysis of cellular cross-talk reveals a role for SEMA6D-TREM2 regulating microglial function in Alzheimer’s disease | Science Translational Medicine www.science.org/doi/10.1126/...

Our latest review on the role of CSPα/DNAJC5 in neurodegenerative dementia #ANCL #Alzheimer #Parkinson #ALS #Huntington by a postdoc in the lab: Dr. Matthew Rosene @bidmcreseach.bsky.social @harvardmed.bsky.social via npj dementia www.nature.com/articles/s44...

Thanks to @erictopol.bsky.social for highlighting our study, led by Dr. @wrannlab.bsky.social , @mgbresearch.bsky.social & @harvardmed.bsky.social , with contributions from @tuckernr.bsky.social , @renhaol.bsky.social , & @kastanenka.bsky.social

Protective exercise responses in the dentate gyrus of Alzheimer’s disease mouse model revealed with single-nucleus RNA-sequencing - Nature Neuroscience Dissecting the adaptive exercise response of the neurogenic stem-cell niche in the dentate gyrus by single-nucleus RNA sequencing reveals the molecular mediators that underlie exercise’s protective ef...

Our latest collaboration on exercise & #Alzheimer's using #sn-RNA-Seq with Dr. Christiane Wrann @wrannlab.bsky.social @mgbresearch.bsky.social @harvardmed.bsky.social via @bidmcreseach.bsky.social @natneuro.nature.com www.nature.com/articles/s41...

JCI Insight - Stearoyl-CoA-Desaturase Inhibition normalizes brain lipid saturation, alpha-synuclein homeostasis, and motor function in mutant Gba1-Parkinson mice insight.jci.org/articles/vie...

TREM2 Activation by First-in-Class Direct Small Molecule Agonists: DEL Screening, Optimization, Biophysical Validation, and Functional Characterization https://www.biorxiv.org/content/10.1101/2025.05.22.655617v1

Excellent editorial by Dr. Saper on orexins in narcolepsy. @harvard-bidmc-pd.bsky.social @bidmcreseach.bsky.social @harvard.edu

Mechanism of Tau protein incorporation into exosomes via cooperative recognition of KFERQ-like motifs by LAMP2A and HSP70 Aggregates of the tau protein is a well-known hallmark of Alzheimer's disease (AD) and other Tauopathies, such as Frontotemporal dementia (FTD). Tau c…

Mechanism of Tau protein incorporation into exosomes via cooperative recognition of KFERQ-like motifs by LAMP2A and HSP70 www.sciencedirect.com/science/arti...

SLC38A9 is directly involved in Tat-induced endolysosome dysfunction and senescence in astrocytes Cellular senescence contributes to accelerated aging and the development of various neurodegeneration disorders including HIV-associated neurocognitive disorders. The development of HIV-associated neu...

SLC38A9 is directly involved in Tat-induced endolysosome dysfunction and senescence in astrocytes www.life-science-alliance.org/content/8/7/...

Rapid Response Bridge Funding Program In the face of recent abrupt shifts in federal funding for education research, including large-scale terminations of National Science Foundation (NSF) research grant awards, we have developed a rap...

I’m generally a cynic. Glass half empty kind of guy. But then I see something like this and think…there are good people out there. be positive and have hope. There is light in darkness. Early career scientists are being prioritized. Take a look! 🧪

www.spencer.org/grant_types/...

Cool stuff by the @malutansey.bsky.social lab

SLC7A11 is an unconventional H+ transporter in lysosomes SLC7A11 acts as an unconventional proton exporter in lysosomes regulating proteolytic degradation, ferroptotic cell death, and Parkinson’s disease pathology.

www.cell.com/cell/fulltex...

SMAD3 and PINK1 constitute a new positive feedback loop in regulation of mitophagy Mitophagy, selective degradation of dysfunctional mitochondria by the autophagy-lysosome pathway, is critical for maintaining cellular homeostasis. In recent years, significant progress has been ma...

SMAD3 and PINK1 constitute a new positive feedback loop in regulation of mitophagy www.tandfonline.com/doi/full/10....

Lysosomal TPC2 channels disrupt Ca2+ entry and dopaminergic function in models of LRRK2-Parkinson’s disease rupress.org/jcb/article/...

Characterization of Isolated Human Astrocytes from Aging Brain www.mdpi.com/1422-0067/26...

Lysosomal Dysfunction in Amyotrophic Lateral Sclerosis: A Familial Case Linked to the p.G376D TARDBP Mutation www.mdpi.com/1422-0067/26...

Sphingolipidoses: expanding the spectrum of α-synucleinopathies - Journal of Neural Transmission Although α-synuclein pathology is typically associated with Lewy body diseases and multiple systems atrophy, increasing evidence indicates that it also occurs in a group of lysosomal storage disorders...

Sphingolipidoses: expanding the spectrum of α-synucleinopathies link.springer.com/article/10.1...

Phase I trial of hES cell-derived dopaminergic neurons for Parkinson’s disease - Nature Bilateral grafts of cryopreserved human embryonic stem cell-derived dopaminergic neuron progenitor cells into the putamen of patients with Parkinson’s disease in a phase I clinical trial sho...

Phase I trial of hES cell-derived dopaminergic neurons for Parkinson’s disease www.nature.com/articles/s41...

Progranulin deficiency in the brain: the interplay between neuronal and non-neuronal cells - Translational Neurodegeneration Heterozygous mutations in GRN gene lead to insufficient levels of the progranulin (PGRN) protein, resulting in frontotemporal dementia (FTD) with TAR DNA-binding protein 43 (TDP-43) inclusions, classi...

Progranulin deficiency in the brain: the interplay between neuronal and non-neuronal cells translationalneurodegeneration.biomedcentral.com/articles/10....

Lysosomal lipid peroxidation contributes to ferroptosis induction via lysosomal membrane permeabilization - Nature Communications The early events in ferroptosis are not clear. Here, the authors report that intra-lysosomal lipid peroxidation (LPO) induces lysosomal membrane permeabilization (LMP) and consequent iron leakage, fos...

Lysosomal lipid peroxidation contributes to ferroptosis induction via lysosomal membrane permeabilization www.nature.com/articles/s41...

Biochemical and Genetic Testing of GAA in Over 30.000 Symptomatic Patients Suspected to Be Affected With Pompe Disease Pompe disease (PD) is a rare autosomal recessive lysosomal disorder caused by loss-of-function of the α-glucosidase (GAA) gene. The deficient GAA enzyme activity may result in potential life-threaten...

Biochemical and Genetic Testing of GAA in Over 30.000 Symptomatic Patients Suspected to Be Affected With Pompe Disease onlinelibrary.wiley.com/doi/10.1155/...

Glia phagocytose neuronal sphingolipids to infiltrate developing synapses The complex morphologies of mature neurons and glia emerge through profound rearrangements of cell membranes during development. Despite being integral components of these membranes, it is unclear whe...

Glia phagocytose neuronal sphingolipids to infiltrate developing synapses."Disrupting sphingolipid catabolism in glia impairs endolysosomal processing, blocking sphingolipid biosynthesis in neurons & glia disrupts autophagy in glia" #GBA #SMPD1 #Parkinsons #Gaucher www.biorxiv.org/content/10.1...

Targeting RPSA to modulate endosomal trafficking and amyloidogenesis in genetic Alzheimer's disease The “amyloid cascade hypothesis” for Alzheimer's disease (AD) pathogenesis, highlights the accumulation of amyloid-β (Aβ) as a crucial trigger for the…

Targeting RPSA to modulate endosomal trafficking and amyloidogenesis in genetic Alzheimer's disease www.sciencedirect.com/science/arti...

Our lab at the NIH (Bethesda, MD) is looking for postdoctoral fellows to join our team studying the molecular mechanisms of protein trafficking and their links to neurodevelopmental disorders starting on or after 10-1-2025. Send your application to juan.bonifacino@nih.gov. Please share and repost!

Immune checkpoint TIM-3 regulates microglia and Alzheimer’s disease - Nature The immune-checkpoint molecule TIM-3 regulates microglial homeostasis, and its microglial-specific deletion reduced cognitive impairment in a mouse model of Alzheimer’s disease.

Immune checkpoint TIM-3 regulates microglia and Alzheimer’s disease www.nature.com/articles/s41...

Commander complex regulates lysosomal function and is implicated in Parkinson’s disease risk Variants in GBA1 resulting in decreased lysosomal glucocerebrosidase (GCase) activity are a common risk factor for Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Incomplete penetrance o...

Commander complex regulates lysosomal function and is implicated in Parkinson’s disease risk www.science.org/doi/10.1126/...

Quiescent cell re-entry is limited by macroautophagy-induced lysosomal damage To maintain tissue homeostasis, many cells reside in a quiescent state until prompted to divide. The reactivation of quiescent cells is perturbed with…

Quiescent cell re-entry is limited by macroautophagy-induced lysosomal damage www.sciencedirect.com/science/arti...

TFEB and TFE3 regulate STING1-dependent immune responses by controlling type I interferon signaling STING1 is an essential component of the innate immune defense against a wide variety of pathogens. Whereas induction of type I interferon (IFN) responses is one of the best-defined functions of STI...

TFEB and TFE3 regulate STING1-dependent immune responses by controlling type I interferon signaling www.tandfonline.com/doi/full/10....

A novel mouse model of chronic neuronopathic Gaucher disease exhibits Parkinson's disease-like phenotypes Gaucher disease (GD), the most common lysosomal storage disorder, is an autosomal recessive inherited disease caused by mutations in GBA1. It can be c…

A novel mouse model of chronic neuronopathic Gaucher disease exhibits Parkinson's disease-like phenotypes www.sciencedirect.com/science/arti...