Adam Handel

MRC New Investigator

Consultant Neurologist

Current Research

My current research aims to understand clinical features and the molecular immunopathogenesis of neuroinflammatory conditions, with a particular focus on autoimmune encephalitis. I have identified clinical features characterizing several types of neurological conditions mediated by autoantibodies. I have generated high-throughput single-cell sequencing libraries from multiple tissues, including peripheral blood and cerebrospinal fluid, in patients with autoantibody-mediated CNS diseases (Fig. 1).

My research also explores different aspects of thymic biology in both normal development and with genetic disruption of thymic epithelial cell function (Fig. 2). I used functional genomics methods to investigate the mechanisms underlying thymic function and other aspects of adaptive immunity. Through a combination of single cell sequencing and multiplexed spatial proteomics, I aim to understand how T cells with autoreactivity against CNS antigens can escape thymic negative selection.

Previous Research

I used induced pluripotent stem cell models to assess the cellular phenotype of cortical neurons in the context of normal development and neurodegenerative disease. As part of these projects, I applied single cell PCR and sequencing methodologies to in vitro models of corticogenesis. I also analyzed chromatin accessibility data to investigate the genetic mechanisms underlying susceptibility to neurological disease. I collaborated on genomic method development to apply capture sequencing to ultra-low and single cell libraries.

My pre-doctoral research focused on the interactions between genetic and environmental factors in determining susceptibility to multiple sclerosis. I applied a variety of statistical models to epidemiological datasets to dissect out the contribution of latitude, month-of-birth, infectious mononucleosis, vitamin D and smoking to multiple sclerosis prevalence and incidence. I used functional genomics methods, including transcriptomics and ChIP-seq to implicate several molecular mechanisms likely to underlie the effect of vitamin D on the immune system.