Dr David Fear

I am currently researching the molecular mechanisms regulating immunoglobulin heavy chain class switch recombination and somatic hypermutation. In particular, I am focusing on identifying novel transcription factors, chromatin remodelling enzymes and microRNAs that regulate class switching towards IgE; the isotype involved in asthma and allergy. I am also interested in the mechanisms regulating the activity and targeting of the enzyme Activation-Induced Cytidine Deaminase (AID). AID is responsible for initiating immunoglobulin gene diversification by somatic hypermutation and class switching and is thought to be responsible for the mutagenic evens that lead to B cell malignancies.

RESEARCH BACKGROUND

Since finishing my PhD I have focused on investigating the molecular mechanisms that regulate germinal centre reactions and in particular what directs immunoglobulin class switching to IgE in human B cells. To this end, I have previously extensively studied the chromatin and transcriptomic landscape of the human Ig heavy chain locus in human (primary) B cells (Fear et al., 2004; Chowdhury et al., 2008; Dayal et al., 2011; Nedbal et al 2012). This work has been part of a longstanding collaboration with Dr Gary Felsenfeld at the National Institutes of Health (USA) and Professor Hannah Gould (King’s College London) and more recently Professor William Cookson (Imperial College London). These studies have now progressed to the genome-wide analysis of various epigenetic marks by ChIP-seq methodologies, transcriptomic studies of human B cell populations (Zhang et al 2016, Shankar-Hari M et al 2017) and how this shapes B cell differentiation and GC population dynamics (Ramadani et al 2017 & 2015). In particular, I am currently focusing on identifying novel transcription factors, chromatin remodelling enzymes and microRNAs that regulate class switching towards IgE (Recaldin et at 2018). I am also interested in the mechanisms regulating the activity and targeting of the enzyme Activation-Induced Cytidine Deaminase, a key enzyme initiating the B cell germinal centre reactions (Fear et al., 2013). Whilst I haven’t got a formal background in bio-informatics/bio-statistics these studies have necessitated me to acquire a good level of understanding and capability in these areas allowing me to fully process and analyse all genomic data acquired and lecture on this subject (Adv. Mol. Genet.). In addition to my own research I have also actively supported many studies by various collaborators in these areas (Kaushik et al., 2005; Kerr  et al., 2005; Kerr et al., 2008; Karagiannis et al., 2013; Gevaert et al., 2013, Saul et al., 2016, Zhao et al.,2017, Shim et al., 2018).