Contact information
Research groups
Colleges
Websites
-
NIHR
Funding body
-
Wellcome Trust
Funding body
-
MRC
Funding body
Figure 1 Single cell sequencing of B cells from NMDA receptor antibody encephalitis
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.
Key publications
-
Journal article
Al-Diwani A. et al, (2022), Brain, 145, 2742 - 2754
-
Developmental dynamics of the neural crest-mesenchymal axis in creating the thymic microenvironment
Journal article
HANDEL A. et al, (2022), Science Advances
-
Journal article
ROTA I. et al, (2021), Science Advances
-
Journal article
Handel AE. et al, (2018), Nature Reviews Neurology, 14, 723 - 734
-
Journal article
Žuklys S. et al, (2016), Nature Immunology, 17, 1206 - 1215
Recent publications
-
Journal article
Klein F. et al, (2023), Nat Commun, 14
-
Journal article
Varley JA. et al, (2023), J Neurol
-
Journal article
Lucas B. et al, (2023), Nature Communications, 14
-
Journal article
HANDEL A. et al, (2023), JAMA Neurology
-
Journal article
White AJ. et al, (2022), J Immunol