Vikram Khurana

Vikram Khurana

Assistant Professor of Neurology
Vikram Khurana
Neurodegenerative diseases like Alzheimer’s and Parkinson’s disease are diseases caused when proteins abnormally fold and aggregate in specific cell types of the central nervous system. Cellular pathology results from a complex interplay of the host (genome and cellular proteome) with a protein folded into a specific, toxic conformation or “strain." The Khurana Lab (khuranalab.bwh.harvard.edu) utilizes unbiased genetic and spatial (proximity labeling) mapping methods to systematically dissect this host-strain interaction. These approaches include genome editing and genome-wide genetic screens, in conjunction with proteome and protein-protein interaction mapping techniques. We predominantly use neurons, glial-neuronal co-cultures and organoids derived from patient induced pluripotent stem (iPS) cells as a model system. However, we also study proteinopathies in the genetically tractable baker’s yeast system (Saccharomyces cerevisiae) to guide our hypotheses and experimentation. The lab is particularly interested in the misfolding of alpha-synuclein, the protein that underlies a group of degenerative brain diseases known as synucleinopathies, that includes Parkinson’s disease, multiple system atrophy and dementia with Lewy bodies. Recently, we have extended our interest to spinocerebellar ataxias and repeat expansion proteins. In previous work, we succeeded in identifying and reversing early, innate cellular pathologies in Parkinson patient-derived neurons harboring alpha-synuclein mutations (Chung, Khurana et al., Science 2013; Tardiff et al. Science 2013). We generated the first comprehensive genetic and spatial maps of alpha-synuclein proteinopathy in living cells (Khurana, Chung, Peng et al., Cell Systems 2017; Chung, Khurana et al., Cell Systems 2017). In these studies, we uncovered an unexpected connection between alpha-synuclein and perturbed mRNA metabolism, as well as genetic interactions between alpha-synuclein and other proteins underlying distinct neurodegenerative diseases. These relationships are now being actively investigated in the lab. For example, we have identified a new direct cytoplasmic function for alpha-synuclein within ribonucleoprotein complexes and believe this work (currently in revision) provides a paradigm through which intrinsically disordered proteins mediate cross-compartment cellular communication in the cell. More translationally, our molecular networks are being harnessed to better understand the genetic architecture and host-strain relationships of synucleinopathies in humans. Finally, coming full circle back to the patient, we are utilizing our stem-cell models to stratify patients for small-molecule and antisense oligonucleotide treatment. Vik Khurana is a PI on two such clinical trials.

Contact Information

Brigham and Women's Hospital
Building for Transformative Medicine, BTM 10016L
60 Fenwood Road
Boston, MA 02115
p: 617-525-5218

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