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Holm Uhlig

Principal Investigator 

 

The gastrointestinal immune system has evolved to avoid and counteract the invasion of pathogens. To allow a strong inflammatory immune response during infection but avoid tissue damage there is a need for effective immune regulation. Defects in immune regulation lead to immunopathology such as inflammatory bowel disease or celiac disease.

About one fifth of all patients with IBD present with initial symptoms during childhood and adolescents. In particular in the very young children patients an underlying immunodeficiency may cause IBD-like symptoms. The analysis of immune deviation in children with IBD and IBD-like symptoms may contribute to the understanding of the complex puzzle of molecular mechanisms involved in IBD.

To investigate novel genetic defects to lead to very early onset intestinal inflammation we established the COLORS in IBD study (COLitis of early Onset - Rare diseaseS withIN IBD). COLORS in IBD has several international collaborators. In collaboration with the Sanger Center Cambridge and the Wellcome Trust Center of Human Genomics (WTCHG) Oxford we investigate patients with pediatric onset of IBD using next generation sequencing.

A further area of interest is the immune response in patients with defects in the PI3K signalling pathway. One large group of patients with defects in this pathway have mutations in the phosphatase PTEN. Due to heterozygous mutations in the PTEN gene patients develop the PTEN hamartoma tumor syndrome which includes Bannayan Riley Ruvalcaba syndrome and Cowden's syndrome. We investigate the functional consequences of PTEN deficiency for the development of the mucosa associated lymphoid tissue, B and T cell responses.

 

Sumeet Pandey

Postdoctoral Scientist

 

I received my PhD in Biochemistry working on the genetic engineering of a probiotic E. coli strain. During my PhD I received a grant to extend my studies from animal models to the human immune system in Holm Uhlig lab based at Oxford. In Oxford, initially I worked on the role of NADPH oxidase 1 in maintaining gut barrier function. My current interest is to investigate the role of anti-bacterial autophagy in the spectrum of monogenic forms of inflammatory bowel disease patient including XIAP, NOD2, CGD and NPC1. We employ small molecule inhibitors/activators and CRISPR technology to study differential autophagy pathway. 

Research Interests: The role of enzymes that generate reactive oxygen species in maintaining gut barrier function

Current project: Role of autophagy in monogenic forms of Inflammatory bowel disease

 

Dominik Aschenbrenner

Postdoctoral Scientist

 

While performing my diploma studies in Microbiology and Genetics at the University of Vienna, I soon got fascinated by the diversity and complexity of the research field of Immunology. Therefore I chose to focus on studying host-pathogen interaction, vaccinology and adjuvant research for the final stage of my undergraduate studies and my diploma thesis project.

After my graduation in Vienna, I wanted to pursue my interests in life science research while specifically focusing on human T cell immunology, for which I joined the Cellular Immunology group of Dr. Federica Sallusto at the Institute for Research in Biomedicine (IRB) as a doctoral student.

During my time at the IRB and the Swiss federal institute of technology Zürich (ETHZ), I had the great chance to study human T cell differentiation, pathogen specificity, phenotype, and function, in the context of host-pathogen interaction and autoimmunity, at the cellular and molecular level. More specifically, my doctoral studies were focused on the ontogeny of pro- and anti-inflammatory phenotypes of human memory Th17 cells, and the regulation of these diverse functional subclasses on the molecular level. Subsequent to my graduation at the ETHZ I wanted to continue working in the field of host-pathogen interaction and autoimmunity while maintaining a strong focus on human immunology and combining cellular and molecular experimental approaches as well as connecting basic research with clinically translational aspects.

Research Interest: 

My research at the Translational Gastroenterology Unit is concentrated to develop a better understanding of immune mechanisms, mediators and cell types that contribute to the pathology of inflammatory bowel disease (IBD).

I am particularly interested in combining rare disease genetics that present with (very) early onset intestinal inflammation with common genetic variation in adult IBD patients to study immune regulation pathways that are critical for the development of IBD and may inform patient stratification and novel treatment strategies for personalized medicine.

Current projects:

- Regulation of cellular sources and production of IL-23 in IBD

- Analysis of genetically identified immune regulation pathways in IBD

- Rare disease genetics and primary immunodeficiency

 

ORCID:              https://orcid.org/0000-0001-7580-2567

Researchgate:    https://www.researchgate.net/profile/Dominik_Aschenbrenner

Linkedin:            https://www.linkedin.com/in/dominik-aschenbrenner-9a6263132

 

Hebe Chen

Postdoctoral Scientist

 

I undertook my PhD in immunology at King’s College London and briefly worked there as a research associate before joining Professor Holm Uhlig’s lab in 2017. I am currently funded by the Oxford-Bristol Myers Squibb fellowship, and co-supervised by Professor Holm Uhlig and Dr. Arian Laurence. My research currently involves 2 projects, both of which are related to GP130 and STAT3.  

My main focus investigates a spectrum of GP130-associated Mendelian diseases where mutations of GP130 (encoded by IL6ST) cause distinct and extreme clinical phenotypes. We use these Mendelian disorders to define genotype-phenotype associations, where we investigate its functional impact on GP130-depdenent cytokine signalling pathways and relate those to clinical phenotypes. Furthermore, we collaborate with structural biologists to more comprehensively understand how structural changes can explain functional consequences for each unique mutation. These phenotypes inform on differential contribution of GP130-dependent cytokines and understand GP130 as a potential drug target. 

The second project aims to investigate signalling downstream of the GP130 and IL-10 cytokine families (IL-6, OSM versus IL-10, IL-22), both of which signal through STAT3, yet have contrasting effects. We aim to understand how STAT3 is able to generate both pro- and anti-inflammatory responses, in the hope to generate novel anti-inflammatory therapies that would target inflammatory responses downstream of the cytokine specifically while preserving the others. 

ORCID: https://orcid.org/0000-0002-8890-691X

 

Melania Capitani

Postdoctoral Scientist

 

I performed my Master thesis and my PhD at the University of Camerino (Italy), where I mainly focused on the development of DNA vaccines for cancer and other chronic diseases. My PhD project was partially performed at Vaxine LTD-Flinders University-Australia and was based on the development of a DNA-based adjuvant to potentiate the response of DNA vaccines in mouse models. After my first PostDoc in Italy, I took the opportunity to apply my Molecular Biology background in the context of IBD at the Uhlig Lab, where I am currently doing my post-Doc.

Research Interests: 

Investigating the anti-bacterial response in macrophages from patients with monogenic disorders.

Current projects: 

- Generation of iPS derived macrophage knockouts for genes involved in the onset of monogenic IBD using CRISPR/Cas technology, which will elucidate the molecular mechanisms behind these disorders and aid in finding potential therapeutic approaches

- Investigation of molecular mechanisms behind DNAse2 deficiency

 

Aline Azabdaftari

 

 

Arian Laurence

Postdoctoral Research Scientist

I received my degrees in biochemistry (1990) and medicine (1993) from UMDS, London University, London UK and subsequently obtained my doctoral degree in 2004 in Immunology and hematology at University College London while working at the London research (now Crick) institute, Cancer research UK at the laboratory of Dr Doreen Cantrell. I have eight year’s post-doctoral research training at NIAMS in the laboratory of Dr John O'Shea where I worked on the role of JAK/ STAT signaling in T helper cell lineages.

Current project: I currently work on the role of BACH2 in human T and B cell development and its relationship with colitis and chronic variable immunodeficiency.

 

Athena Cavounidis

DPhil Student

I completed my undergraduate degree in Biochemistry and Molecular Biology, during which immunology captivated me. I hence decided to pursue this interest further through the MSc in Integrated Immunology, carrying out my master’s thesis in Holm Uhlig’s lab. During this time I worked on modelling phagocyte defects using iPS cells and bacterial handling defects in inflammatory bowel disease, projects that I continued to work on as a research assistant in the lab. I am now a DPhil student interrogating defective anti-microbial pathways in Hermansky-Pudlak Syndrome.

Research Interests: 

Cell-autonomous defense; mechanisms governing innate immunity

Current projects: 

Hermansky-Pudlak Syndrome results in oculocutaneous albinism, bleeding diathesis and in some cases lung fibrosis and granulomatous colitis. Patients have defects in the biogenesis of lysosome-related organelles, and we are trying to identify and characterize the pathways involved in order to elucidate the mechanism of inflammatory bowel disease in these patients. 

 

Melanie Dunstan

Postdoctoral Research Scientist

 

I joined the Uhlig group in 2017 as an Oxford-Bristol Myers Squibb (formerly Celgene) Fellow.  I am also a member Diabetes and Inflammation laboratory (Wellcome Centre for Human Genetics).

My research is focused on single-cell analysis of gut-resident T cells in type 1 diabetes and coeliac disease. In addition, I am determining the responses of gut-resident regulatory T cells to Bristol Myers Squibb’s novel IL-2 mutein Fc fusion protein.

Prior to this, I undertook PhD and post-doctoral research in the UK Dementia Research Institute in Cardiff (Alzheimer’s Disease Group). During this time, I developed cell models to interrogate the biological mechanisms underpinning genetic loci associated with late-onset Alzheimer’s disease.

 

Joanneke Jansen

DPhil Student

 

Tom Thomas

DPhil Student

 

Boryana Galabova

Research Assistant

 

I undertook a BSc degree in Biological Sciences at the University of Toulon in France during which I became very interested in Immunology. Therefore, I decided to pursue a Master’s degree in Integrated Immunology and I joined Uhlig’s group in April 2020 to carry out my master’s thesis in Uhlig’s lab. During my project, I investigated how cellular immune responses towards different viral and bacterial pathogens involve the endosomal pathways. The results bridge the gap between the virology and bacteriology fields and provide new insights into how viruses and bacteria use the endosomal pathway to infect cells.

Since October 2020, I’ve been working in the lab as a research assistant. Currently, I am working on a project that aims to define the cellular basis of joint and gut inflammation in paediatric cohorts of inflammatory bowel disease and juvenile idiopathic arthritis by analysing target tissue using an integrated systems-based approach. We aim to develop a cellular atlas of each tissue, with the geographic distribution of cells and gene expression profiles for inflamed tissues across these two diseases, and highlight both similarities and differences in the cellular basis of inflammation.

 

Lisa Gartner

Research Assistant

 

I first joined the group in 2019 for a research internship after I had graduated from the Technical University of Munich with a BSc in Nutritional Sciences. During those four months I was working on the GP130 project and investigating how mutations in the gene are affecting the protein's stability and functionality. As I found the immunological aspects of the project very captivating, I decided to stay in Oxford and study for an MSc in Immunology. In August, I re-joined the group as a Research Assistant, now working on Environmental Enteropathy and the role of TLR4 and LPS in the induction of intestinal inflammation.