Overview
My lab investigates pathogenesis of age-dependent neurodegenerative diseases, like Alzheimer's disease and Parkinson's disease, at the cellular-molecular level. To study these diseases, we combine biochemistry, cell biology, mouse genetic models and mouse behavior.
Short-term GoalsNeurodegenerative diseases are associated with varied genetic and environmental factors, yet age remains a universal risk factor. Age-associated failure of protein homeostasis, or “proteostasis”, causes disease-linked proteins to misfold into non-physiological oligomers and aggregates, producing a myriad of cellular dysfunctions. Long lifetime of a neuron enhances the need for proteostatic mechanisms, such as molecular chaperones that stabilize native protein folds and degradation pathways that eliminate misfolded proteins. My lab is interested in the mechanisms that mediate proteostasis in neurons and how their failure over time leads to neurodegeneration.
We are investigating this topic by:
a) Studying how proteostasis of Tau protein is regulated by two co-chaperones of Hsc70: CHIP (C-terminus of Hsc/Hsp70 interacting protein) and CSP-α (cysteine string protein-α).
b) Investigating how neurodegeneration is caused by recently found human mutations in CSP-α which cause neuronal ceroid lipofuscinosis, an adult-onset neurodegenerative disorder.
c) Comparing lysosomes from brains of normal mice and from neurodegenerative mouse models to identify changes that accompany the decline of neuronal proteostasis.
Our research will uncover proteostatic mechanisms in neurons which allow them to live and function for a lifetime, and how these mechanisms fail in aging neurons. Understanding neuronal proteostasis in health and disease may lead to treatment strategies for multiple neurodegenerative disorders, like Parkinson’s disease and Alzheimer’s disease, which share age-dependent proteostatic defects.
Highlights
- 1Nature communications · 2022
- 2Nature structural & molecular biology · 2020
Publications
Funding
Active
5 grants- MPIR01NS136423-01A1Changes in synaptic vesicle-binding of alpha-synuclein as an early biomarker for synucleinopathiesNational Institute of Neurological Disorders and Stroke · 2024–2029
- MPIR01AG083949-03Tau proteostasis by chaperone-complexes in tauopathies including Alzheimer's diseaseNational Institute on Aging · 2024–2029
- Co-IRF1AG084635-01A1Small molecule inhibitors of CAPON-induced tau aggregationNational Institute on Aging · 2024–2027
- KPF31NS143430-01A1Mechanism and rescue of lysosomal defects in Adult-onset Neuronal Ceroid LipofuscinosisNational Institute of Neurological Disorders and Stroke · 2025–2027Fellowship
- MPIR01NS126342-02The impact of beta- and gamma-synucleins on alpha-synuclein's synaptic functionNational Institute of Neurological Disorders and Stroke · 2022–2027
Completed grants (4)
- PIR01NS095988-05Cellular Mechanism of Adult Onset Neuronal Ceroid Lipofuscinosis (ANCL) Caused by Mutations in Cysteine String Protein-Alpha (CSPalpha)National Institute of Neurological Disorders and Stroke · 2017–2025
- PIR01AG052505-05DnaJ Co-Chaperones Which Modify Tau Aggregation and NeurodegenerationNational Institute on Aging · 2016–2024
- KPF31AG069416-01Biophysical Characterization of Covalently Modified Protein Tau: Oligomers, Aggregation, and Tubulin InteractionsNational Institute on Aging · 2020–2022Fellowship
- KPF31NS098623-02Disease Causing Mutations in Cysteine String Protein-Alpha Disrupt SNARE-Dependent Lysosomal ExocytosisNational Institute of Neurological Disorders and Stroke · 2017–2020Fellowship
Available technologies
News mentions
- Looking Beyond Beta-Amyloid: New Paths in Alzheimer's ResearchJune 3, 2025
At the 12th annual Helen and Robert Appel Alzheimer’s Disease Research Institute Symposium, scientists and clinicians shared their latest research which is advancing how Alzheimer’s disease is diagnosed and treated.
- Discovery Illuminates How Parkinson’s Disease Spreads in The BrainSeptember 20, 2022
Aggregates of the protein alpha-synuclein spread in the brains of people with Parkinson’s disease through a cellular waste-ejection process, suggests a new study led by Weill Cornell Medicine researchers.
- New Developments in Dementia Research Presented at Appel Alzheimer's Disease Research Institute SymposiumOctober 26, 2020
Investigators on the forefront of research into neurodegenerative disorders shared some of their latest discoveries and possible implications for treatment at the eighth annual Appel Alzheimer's Disease Research Institute Symposium, held remotely on Oct. 14.
Mentoring
- NNNima NaseriNeuroscience (PhD) · Class of 2020
- ARAditya RaoNeuroscience (PhD)
- BBBergan BabrowiczNeuroscience (PhD)
- JMJacqueline McAleerNeuroscience (PhD)
- SMSamantha McDonoughNeuroscience (PhD)