People | Lehner Lab

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Current Member

Professor Paul Lehner

Paul Lehner is Professor of Immunology and Medicine at the University of Cambridge, a Wellcome Trust Principal Research Fellow, and Honorary Consultant in Infectious Diseases at Cambridge University Hospitals. Paul trained in medicine and infectious diseases. His work sits at the interface between virology, immunology and cell biology and he uses functional genetic and proteomic technologies to study how viruses interact with, and evade recognition of, the human immune system.

Dr. Alexandra Rowland (Clinical PhD Fellow)

I am a senior registrar in Obstetrics and Gynaecology, having completed my medical training at Cambridge University. I am currently undertaking my PhD in the Lehner Laboratory as a Wellcome Trust Clinical Fellow. I am investigating the regulation of HLA-G on the surface of placental extra-villous trophoblast cells and how this may be linked to trophoblast differentiation.

Trophoblast cells in the human placenta form the interface between the mother and fetus throughout pregnancy. They must communicate with the maternal immune system to result in the ‘immunological tolerance’ of pregnancy. A failure of these mechanisms results in diseases of placental origin (pre-eclampsia, inter-uterine growth restriction and recurrent miscarriage) as the maternal immune system might recognise and respond to the placenta as a foreign organism. HLA-G is a unique immune molecule which is only expressed on a subset of trophoblast cells called extra-villous trophoblast (EVT) and is involved in generating maternal 'tolerance'.

I am using CRISPR gene-editing technology and proteomics to identify the genes that regulate the expression of HLA-G in placental models. We aim to develop a new understanding of pregnancy disease that will pave the way for novel treatments.

Aneisha Duggal (PhD Student)

I am a second year PhD student in the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) programme in the Lehner Lab. I am currently investigating a novel inflammatory disorder called VEXAS syndrome, which is associated with high morbidity and has limited options for treatment. VEXAS syndrome results from somatic mutations in UBA1, the rate limiting step for initiating ubiquitination. I am interested in identifying mechanisms through which specific cells are able to compensate for proteotoxic stresses associated with dysregulation of the ubiquitin-proteasome pathway, as well as identifying genetic weaknesses associated with these cells in the hopes to translate them into therapeutics. In my spare time, I enjoy playing the piano and painting.

Jun Zhan (PhD Student)

I am a fourth year Cambridge MB/PhD student. My research interest lies in understanding the interaction between viruses and their hosts – more specifically how SARS-CoV-2 gets into human cells and what can we do to prevent it.

To this end, I am using genetic approaches to identify the protein complexes which regulate the expression of the human ACE2 receptor (SARS-CoV-2 entry receptor) on the cell surface, and to elucidate the mechanism of this regulatory process so that we can hopefully modulate ACE2 expression and impact viral cell entry efficiency.

Jonathan Cohen-Gold (PhD Student)

I’m a PhD student on the MRC Doctoral Training Programme and my project explores the domestication of invading genes. I’m interested in determining how newly-acquired genes escape immunosurveillance by HUSH, a protein complex which defends our genome from attack by silencing foreign genetic material. Specifically, I probe the mechanistic relationship between HUSH-evasion and RNA processing pathways, with a particular interest in nuclear RNA export factors.

Before coming to the lab, I completed my undergraduate study at King's College London, studying Molecular Genetics and Pharmacology. I keep busy outside of the lab by writing and performing music, playing football and enjoying Darwin College life.

Niek Wit (Bioinformatician)

I am a Bioinformatician working in the groups of both Prof Paul Lehner and Prof James Nathan. Originally I was trained as molecular biologist (MSc Free University Amsterdam) and I obtained my PhD from the University of Amsterdam for research conducted at the Netherlands Cancer Institute in the lab of Dr. Heinz Jacobs.

Here I studied how ubiquitination controls DNA damage tolerance. For my postdoc I moved to the Laboratory of Molecular Biology (Cambridge, UK) to join the lab of Prof KJ Patel, where I became interested in how metabolism contributes to DNA damage. Since 2020 I have worked at CITIID as a Bioinformatician in the group of Prof James Nathan, and since 2023 for Prof Paul Lehner as well.

My current work involves analysing a variety of large biological data sets and developing analysis pipelines (using Python, R and Shell scripting), as well as providing ad hoc bioinformatics support.

In my free time I like to program/mess around with Raspberry Pi(s), read history books, and spend time with my family in the countryside.

Dr. James Williamson (Research Associate)

I am a research associate and I provide mass spectrometry-based proteomics expertise for the lab and our collaborators. As well as various standard approaches such as affinity purification – mass spectrometry and TMT based quantification of whole cell proteomes I specialise in proteomic analysis of the plasma membrane – a technique we call plasma membrane profiling.

I have applied these proteomic techniques to the analysis of human pathogenic viruses such as HIV, SARS-CoV2, KSHV, CMV and EBV. I’m also continually working on method development projects, testing new techniques and iterating current methods to improve performance and ease of use.

Dr. Ildar Gabaev (Research Associate)

My major area of interest is virology, particularly, interaction of viruses with the host cells. I am also interested in developing tools that facilitate the identification and functional characterisation of viral genes that mediate immune evasion.

I joined the Lehner lab to investigate how human endothelial cells are changed by lytic Kaposi-Sarcoma-associated herpesvirus infection using a quantitative proteomics approach. With the beginning of the COVID-19 pandemic, I started investigating the mechanisms of regulation of cellular receptors for SARS-CoV-2 entry using forward genetics.

Dr. Samuel Watson (Research Associate)

My research projects interrogate different aspects of the ubiquitin proteasome system, which is the major pathway for selective protein degradation in eukaryotic cells. This versatile theme links the projects of my otherwise varied research career. I completed my DPhil at Oxford, where I investigated the regulation of a ubiquitin-dependent pathway that protects plants from environmental stress. I then moved to the Lehner Lab, where I dramatically changed fields, from plant genetics to biochemistry and mammalian cell biology. I am currently involved in two research projects, one more basic, and one more translational. In the first, I am exploring the diverse mechanisms that underpin substrate recognition by the ubiquitin proteasome system.

In the second (which is being driven by Aneisha Duggal), we are characterising a severe, ubiquitin-related, autoimmune disease. More specifically, we are aiming to identify actionable drug targets using forward genetics and sophisticated cell models. The projects are technically varied, involving powerful discovery platforms (e.g. advanced proteomics, CRISPR screens) as well as techniques required for the detailed characterisation of the resulting hits (e.g. precise genome editing, in vitro reconstitution of pathways with purified factors). Through these and other projects, I seek answers to two broad questions: How does the ubiquitin proteasome system selectively and/or conditionally identify its targets? And, how do defects in the pathway cause dysfunction and disease?

Dr. Sam Watson (Research Associate)

Dr. Stuart Bloor (Research Associate)

I am a research associate, with significant experience of studying the mechanisms of HIV-1 and HBV drug resistance, at St Mary’s Hospital, The Wellcome Foundation, GlaxoWellcome, as a co-founder of Virco UK Ltd and later at Visible Genetics Inc. More recently I worked in Dr Felix Randow’s laboratory (LMB), studying the role of ubiquitin in NF-kB signalling.

Since joining the Lehner laboratory I’ve worked on a variety of projects starting with the role of signal peptide peptidase in the ER-associated degradation of of tail-anchored proteins. Most recently I have been studying the role of Periphilin in the establishment and maintenance of silencing by the HUSH complex as well as improving the potency of our novel HUSH inhibitor.

Dr. Chris Gawden-Bone (Research Associate)

I completed my PhD at the university of Dundee where I investigated the ultrastructure of podosomes, the actin-rich organelles that form on the ventral plasma membrane of myeloid and monocyte derived cells. On completion of my PhD, I continued these studies looking into the role played by integrins in the formation of podosomes.

I left Dundee for the Cambridge Institute of Medical Research to take up a post doc to study the role of phospholipids in the target killing, undertaken by cytotoxic T cells. I am currently a Research Associate at the Cambridge Institute of Therapeutic Immunology and Infectious Disease, where I study the role played by RNF145, an E3 ubiquitin ligase, on the expression and activity of the lipid hydrolase Adiponectin receptor 2

Tim Young (Lab Manager)

I qualified as a Biomedical Scientist in 2012 after completing my bachelor’s degree at The University of Essex then moved towards research; my first role was a technician with the MRC Epidemiology Unit, here I used a variety of methods to perform batch analysis on large cohorts of samples.

After this I moved into cancer research and worked as a research assistant for Prof. Bruce Ponder in conjunction with the NHS Papworth Histology team. The research was directed towards the investigation of DNA repair dysfunction which can cause a genetic predisposition to lung cancer, particularly in smokers.

Then, in 2016, I joined the lab of Christian Frezza at Uni. Of Cambridge as part of the mass spectrometry team before becoming the lab manager and microscopist. When the lab moved out of the country I joined Prof. Paul Lehner’s team in CITIID and am continuing my RMS diploma here.