AlzhEimer's Disease: Next Generation Researchers
This multi-institutional seminar series highlights team members representing the “next generation” of researchers. Their work contributes to the understanding of Alzheimer’s disease mechanism, with the goal of improving diagnosis and treatment.
Alessandra Chesi, PhD
Variant-to-gene mapping for brain-related traits and disorders
Variant-to-gene mapping for brain-related traits and disorders
While genetic studies have revealed many variants in the human genome associated with brain-related diseases such as Alzheimer’s, the culprit effector genes (essential to design effective therapies) remain to be discovered. The main challenges are that 1) because of LD, GWAS identify “signals” and not the underlying causal variants and effector genes; 2) the majority of variants identified by GWAS reside in non-coding regions of the genome and are thought to regulate gene expression, often hundreds of kb away in linear distance and 3) gene expression regulation is exquisitely tissue and cell type specific. To tackle these issues, I propose a “variant-to-gene” mapping campaign leveraging high resolution promoter Capture C and/or Hi-C, plus ATAC-seq and ChIP-seq, in human iPSC-derived neural cell types (neurons, astrocytes and microglia, including co-cultures and brain organoids) from individuals and patients of different sex and ethnicity. This effort will provide targets for drug discovery and begin to address sex and ethnic differences in brain-related diseases, ultimately advancing the goals of precision medicine.

Alessandra Chesi, PhD
Assistant Professor
Department of Pathology and Laboratory Medicine
University of Pennsylvania
Alessandra Chesi, PhD, has focused her career thus far on neurodegenerative diseases. She brings to this work extensive experience in the generation and analysis of large datasets (including high resolution chromatin conformation capture techniques) with a focus on human genetic, epigenetic, and genomic investigations.
As part of her postdoctoral training, she leveraged the power of yeast genetics to unveil the function of a Parkinson’s disease gene, PARK9, and she led a large exome-sequencing project of 47 sporadic ALS trios, identifying a set of potentially pathogenic de novo mutations enriched in chromatin regulator genes including neuronal chromatin remodeling complex (nBAF) component SS18L1.
While at the University of Pennsylvania and Stanford University, she set up bioinformatics pipelines (BWA, GATK, SAMtools, etc.) to analyze next-generation sequencing data. After joining the Center for Spatial and Functional Genomics at the Children’s Hospital of Philadelphia, she conducted genome wide association studies of different traits related to children’s health (bone mineral density and accrual, childhood obesity, early onset forms of type-2 diabetes) and developed and leveraged novel chromatin conformation capture techniques coupled with ATAC-seq to link known GWAS loci to their functional target gene(s).
In her own lab at Penn, she is now focusing on applying these and other cutting-edge genomic techniques to the study of neurodegenerative and brain-related disorders in human cell models.
She is part of the Penn Neurodegeneration Genomic Center (PNGC), a highly interdisciplinary and collaborative center with more than a dozen faculty members who specialize in neurodegenerative disorders and dementia, human genetics, genomics, bioinformatics, and biostatistics.
Find Dr. Chessi’s publications here.
CADRE is administratively housed at Case Western Reserve University with support from all participating academic institutions
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