The Khurana lab uses stem cells, genomic analysis and systems cell biology approaches to better understand and develop patient-specific therapies for Parkinson’s disease, ataxias and related disorders. The lab has created the first proteome-scale cellular “maps” of alpha-synucleinopathy, the hallmark pathology of these diseases. These maps have uncovered new functions for alpha-synuclein, new insights into genetics and pathogenesis and helped advance novel drugs to clinical trial.

Neurodegenerative diseases like Alzheimer’s and Parkinson’s disease are diseases caused when proteins abnormally fold and mislocalize in specific cell types of the central nervous system. The Khurana lab, based in the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital, uses cutting-edge stem cell, genome-editing and in situ proteomic techniques to study how these hallmark protein-misfolding pathologies are related to genetic factors that predispose to these diseases, and how they may be reversed.
 
Research in the Khurana lab addresses four central questions:

1. How does protein misfolding/mislocalization perturb the physiology of within any given cell type of the CNS? How do specific conformations of proteins (monomers, oligomers, amyloid “strains” etc.) impact these effects? Can we “tune” back aberrant protein localization to a more physiologic state? (Chung*, Khurana* et al., Science 2023; Khurana*,  Peng*, Chung* et al., Cell Systems 2017; Chung*, Khurana et al., Cell Systems 2017).

2. How does protein misfolding and localization play out between distinct cells of the CNS, that is in glia-neuronal crosstalk that occurs during neuro-inflammation? Can we model these interactions effectively “in the dish”? How do environmental toxicants like pesticides or microbial metabolites in the gut affect these process? (Paul*, Krolewski* et al., Nature Communications 2023)

3. How does the physiologic function of proteins relate to the toxicity that results when these proteins misfold? We believe both “toxic gain” and “loss” of protein functions are central to neurodegeneration. We are actively testing how closely protein-reducing therapeutics like antisense oligonucleotide(ASO) therapies rescue primary pathologies. In recent studies, we identified a novel and disease-relevant role for the alpha-synuclein protein in regulating mRNA stability and hence gene regulation (Jarosz and Khurana Cell 2017; Hallacli et al. Cell 2022).

The lab’s principal focus is on alpha-synucleinopathies, diseases related to the misfolding and mislocalization of the alpha-synuclein protein that misfolds in Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA), and ataxias caused by polyglutamine repeat-expansion disorders.