One approach to infer causal genes in disease is a transcriptome-wide association study (TWAS). However, TWAS is not powerful in non-European populations due to poor trans-ancestry portability of gene expression prediction models and smaller genome-wide association study (GWAS) sample sizes. The purpose of this project is to develop a novel machine learning approach to mitigate the issue of trans-ancestry portability. This approach will allow for powerful TWAS in non-European populations by simultaneously modeling genetic and genomic data from different populations, which has previously been challenging due to population-specific differences in genetic architecture such as linkage disequilibrium.

We developed a novel tau propagation model using 3D spheroid model that rapidly develop tau pathology and neurodegeneration in just three weeks. Single cell transcriptomics of the model reveals cell type specific changes that resemble transcriptomic signatures from Alzheimer’s disease postmortem brain.

To understand cell type specific vulnerability of Alzheimer’s disease, we utilize snRNA-seq to characterize human brain tissues from Alzheimer’s disease patients across different brain regions.

As part of the NIH NIDA SCORCH consortium, we will dissect the dysregulated molecular circuitry in the brains of individuals with cocaine use disorder and/or HIV infection. This project will focus on understanding how neurovasculature and neuroimmune cells contribute to cocaine use disorder and HIV-associated neurocognitive disorders. We will be generating snRNA-seq and snATAC-seq profiles from more than 300 patient samples across 3 different brain regions.

As part of the NIH NIDA SCORCH consortium, we will dissect the dysregulated molecular circuitry in the brains of individuals with opioid use disorder and/or HIV infection. This project aims to identify genes that contribute to opioid use disorder and HIV-associated neurocognitive disorders. These approaches could lead to novel gene therapies to control and perhaps reverse the relentless disease state. We are in the process of generating snRNA-seq and snATAC-seq profiles from more than 300 patient samples across 3 different brain regions.