Goals of the Lab
The Gate lab in Northwestern Neurology works at the interface of the immune system and neurodegenerative disease. The lab is focused on employing human genomics approaches to uncover novel biomarkers and therapeutic targets for neurodegeneration. Chief among our strategies is single cell RNA sequencing (scRNAseq) to identify transcriptional changes in human specimens. The Gate lab does not utilize animals in our research- we are focused on human disease and human tissues. We also employ spatial transcriptomics, immunohistochemistry and cytometry approaches to validate genomic changes observed by scRNAseq. The Gate lab is focused primarily on neurodegenerative diseases of aging, including, but not limited to: Alzheimer’s disease, Parkinson’s disease and Amyotropic lateral sclerosis.
Mechanisms of amyloid clearance in immunized Alzheimer’s disease patients
The lab is interrogating brains of Alzheimer’s patients who were immunized against amyloid-beta in clinical trials. We employ genomics assays, including spatial and single-cell transcriptomics to understand the molecular mechanisms of amyloid clearance.
T cell epigenetics in Alzheimer’s disease
This project aims to define the genome-wide chromatin accessibility landscape of CD8 T cells in Alzheimer’s disease (AD). We hypothesize that antigen-experienced CD8 T cells contribute to disease via effector-driven antigen control that will be reflected by uncovering specific regions of accessible chromatin. Specifically, we expect to uncover pro-inflammatory genes such as cytokines, chemokines and cytotoxic molecules that will implicate CD8 T cells in AD neuroinflammation. These experiments could elucidate the mechanism by which T cells contribute to AD pathogenesis and may reveal novel immunotherapeutic targets for AD.
Deciphering the molecular alterations to amyotrophic lateral sclerosis immunity
This study will utilize a combination of genomic approaches to assess peripheral and central immunity in C9orf72 expansion carriers. Specifically, this project will test the “dual-effect” mechanism by deciphering the molecular alterations to central and peripheral innate immune cells in C9orf72 expansion carriers. It is hypothesized that C9orf72 expansion alters innate immune function and contributes to neurodegeneration in ALS.