Dr Leonie Unterholzner
Senior Lecturer in Molecular ImmunologyResearch Overview
My research group is interested in how cells can detect foreign DNA, for example when skin cells have been infected by a virus. This is part of the innate immune response, which acts within the first few hours of infection, with the aim to alert more specialised immune cells, and to eliminate the virus before it can spread to other parts of the body. We are investigating how a cell can distinguish viral DNA from its own DNA genome, and how it signals to alert neighbouring cells. We also study how cells can detect their own DNA as danger signal, when the DNA has been damaged by UV light or chemotherapy.
Our work investigates molecular mechanisms that underlie the immune response during infection, autoimmunity and cancer.
Current Research
Current projects in my laboratory focus on the molecular mechanisms of intracellular DNA recognition. Projects include:
- The function of the DNA sensors cGAS and IFI16 in detecting DNA in the cytosol
- The cell-intrinsic innate immune response to DNA damage
- The role of DNA sensing in cancer
- Immune evasion strategies employed by DNA viruses and Leishmania parasites
Current Teaching
I currently teach on the 3rd year module BIOL321 Clinical Immunology and the masters level module BIOL434 Emerging Therapeutics in Immunology. I also supervise undergraduate and postgraduate students during their research projects. I am Director of Studies for postgraduate research students in the Division of Biomedical and Life Sciences, and am co-ordinating a skills and research career development program for PhD students and postdocs.
PhD Supervision Interests
My laboratory works on the innate immune system and host-pathogen interactions. We are particularly interested in the molecular mechanisms of how cells detect DNA in the cytosol, and how nuclear DNA damage and replication stress act as danger signal for the immune system. Some examples of potential Masters by Research projects are: 1. How do poxviruses evade detection by the innate immune system? 2. How is intracellular DNA detected as "stranger" and "danger" signal? 3. Has our innate immune system evolved from ancient anti-viral defences in Archaea? (joint project with Nick Robinson) 4. Does oncogene-induced replication stress drive inflammation in cancer? 5. How are DNA sensing factors activated in autoinflammatory conditions?
Epithelial cells as sentinels in innate immunity
01/10/2023 → 30/09/2024
Research
Investigation of IFI16 modulating molecules on Type I IFN inflammatory mediators following cytosolic DNA sensing or detection of nuclear DNA damage
01/10/2023 → 31/03/2024
Research
STING signalling as link between DNA damaging therapies and innate immunity in bladder cancer
01/12/2022 → 30/11/2025
Research
Talent and Research Stabilisation Fund 2022 (Leonie Unterholzner)
21/11/2022 → 31/03/2023
Research
3 Year Research PhD Studentship: Modulation of the innate immune responses by DNAzymes
04/01/2021 → 30/04/2024
Research
How is the immune system alerted to persistent replication stress and DNA damage in keratinocytes during immunosurveillance against cutaneous squamous cell carcinoma?
01/10/2019 → 30/09/2024
Research
The role of innate immunity in the response to radiation-induced DNA damage in human skin cells
01/02/2019 → 30/04/2019
Research
NWCR Equipment bid: Faxitron CellRad Irradiator
01/10/2018 → 31/03/2019
Research
How does p53 link DNA damage to innate immunity?
01/01/2018 → 31/05/2021
Research
Innate immune recognition of intracellular DNA as 'stranger' and 'danger' signal
01/01/2015 → 31/12/2018
Research
Innate immune recognition of Herpes SImplex Virus in skin cells: Differences between neonatal and adult keratinocytes.
01/08/2014 → 28/02/2016
Research
How do keratinocytes sense the presence of intracellular DNA?
01/02/2014 → 31/08/2015
Research
Elucidating the molecular mechanism of intracellular DNA recognition by the innate immune sensor IFI16
01/02/2013 → 31/07/2018
Research
Regulation of DNA repair and the innate immune response to radio- and chemotherapy by the DNA sensors cGAS and IFI16.
01/01/1900 → …
Research
Nature Structural and Molecular Biology (Journal)
Editorial activity
Cell (Journal)
Publication peer-review
PhD viva Dublin
Examination
Trinity College Dublin
Visiting an external academic institution
PhD viva Liverpool
Examination
Science (Journal)
Publication peer-review
Cell (Journal)
Publication peer-review
Cell Reports (Journal)
Publication peer-review
EMBO Journal (Journal)
Publication peer-review
Royal Society Open Science (Journal)
Editorial activity
Cell Reports (Journal)
Publication peer-review
Invited speaker at "Nucleic Acid Immunity" conference
Invited talk
Dr Abi Spear visiting Lancaster University
Types of Business and Community - Hosting of external, non-academic visitor
Nature Communications (Journal)
Publication peer-review
Hosting Dr Carlos Maluquer des Motes
Types of External academic engagement - Hosting an academic visitor
Invited speaker at "Novel Concepts in Innate Immunity" conference
Invited talk
Invited speaker at "cGAS-STING in Health and Disease" symposium
Invited talk
Cell (Journal)
Publication peer-review
Cell (Journal)
Publication peer-review
Expert Opinion Flagship Pioneering
Expert Opinion
North West Cancer Research Fund (External organisation)
Membership of committee
Selected oral presentation at the British Society for Immunology conference
Oral presentation
Cell Reports (Journal)
Publication peer-review
Invited Seminar at Aarhus University
Invited talk
Cell (Journal)
Publication peer-review
Cell (Journal)
Publication peer-review
EMBO Journal (Journal)
Publication peer-review
Invited speaker at Lupus2021
Invited talk
Invited seminar at the Penn Centre for Genomic Integrity
Invited talk
Invited seminar at the Dept of Oncology, Oxford
Oral presentation
Oral presentation at Keystone Symposium "DAMPS across the Tree of Life"
Oral presentation
Royal Society (External organisation)
Membership of board
Nature Communications (Journal)
Publication peer-review
Nature Immunology (Journal)
Publication peer-review
Invited speaker at EMBO Workshop: Pathogen Immunity and Signalling
Invited talk
Invited speaker at Host-Pathogens Interactions Meeting, Israel
Invited talk
Invited seminar at UCL
Invited talk
British Society for Immunology (External organisation)
Member of an organisation
MRC Career Development Award
Fellowship awarded competitively
Marie Curie IntraEuropean Fellowship
Fellowship awarded competitively
Royal Society Leverhulme Trust Senior Research Fellowship
Fellowship awarded competitively
Marie Curie Career Establishment Award
Fellowship awarded competitively
- Cancer Biology and Genome Stability
- Microbes, Pathogens and Immunity