Our Research
Genetic studies have provided a wealth of variants associated with human complex traits, but are not able to pinpoint the underlying target genes and molecular mechanisms. We are interested in finding the target genes for several brain-related disorders, such as Alzheimer's, Parkinson's and other neurodegenerative disease. To do this, we use a combined wet-bench/bioinformatic approach, leveraging cutting-edge genomics and epigenetic techniques such as Capture C, Hi-C, ATAC-seq, ChIP-seq, and RNA-seq plus custom analysis pipelines and methods to perform a “variant-to-gene mapping” campaign (Figure 1) for these disorders. We follow up candidate culprit variant-gene pairs by CRISPR/Cas9 editing and functional studies in appropriate cellular models of neurodegeneration (Figure 2), such as iPSC-derived neurons (cortical, dopaminergic, etc.), microglia, astrocytes, co-cultures and cerebral organoids (“brain in a dish”). Our ultimate goal is drug discovery for the identified target genes/molecular pathways, utilizing our cellular models of neurodegeneration for drug screens and leveraging system biology approaches.
Team
Distinguished Lab Alumni
Sandhya Ramachandran
Sara Antonuzi
Pranav Ayyappan
Selected Publications
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📔 Selected Publications
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Mapping effector genes at lupus GWAS loci using promoter Capture-C in follicular helper T cells. Su C, Johnson ME, Torres A, Thomas RM, Manduchi E, Sharma P, Mehra P, Le Coz C, Leonard ME, Lu S, Hodge KM, Chesi A, Pippin J, Romberg N, Grant SFA, Wells AD, Nature communications 11(1): 3294, 2020, PMID:32620744