Dr Ana Tiganescu

Profile

I obtained my BSc in Biological Sciences at the University of Warwick in 2005 and developed strong molecular biology laboratory skills through employment at the University of Oxford Weatherall Institute for Molecular Medicine and Wellcome Trust Centre for Human Genetics. After a year nanotechnology industry (Oxonica Ltd.) developing novel biodiagnostic assays and UV suncream enhancers, I joined the University of Birmingham and completed my Ph.D. on Glucocorticoid Metabolism in Ageing Skin in 2011. I then undertook a 2-year Visiting Research Scholarship at the University of California San Francisco where I developed in vivo models of wound healing. In 2014 I joined the University of Leeds where I now continue my research as an Academy of Medical Sciences Springboard Fellow.

Research interests

Over the past 15 years, my research has been fully dedicated to developing a novel treatment for skin wound healing and spans the full translational research pipeline. My Ph.D. characterised stress hormone (cortisol) activation by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) as a novel regulator of skin function. Cortisol (and therapeutic glucocorticoid e.g. prednisolone) excess drives many adverse effects in skin including epidermal thinning, dermal atrophy, impaired wound healing, and increased infection. These effects are mirrored by the skin phenotype in ageing and diabetes, identifying 11β-HSD1 inhibitors as a possible novel therapeutic for these conditions, alongside potential as a shield against detrimental side-effects of long-term glucocorticoid therapy. My skin research has demonstrated translational benefits across all of these areas:

1) For ageing, my Ph.D. research with Professor of Endocrinology Paul Stewart (University of Birmingham) found that skin 11β-HSD1 increases in aged mice and humans, and that 11β-HSD1 KO mice are protected from skin ageing with reversal of age-related changes in certain collagen remodelling enzymes. My interests in this space extend to photo-ageing, where I found elevated 11β-HSD1 activity and induction by UVB.

2) For glucocorticoid toxicity, my research with Professors of Dermatology Peter Elias and Theodora Mauro (University of California San Francisco) found a restoration of healing trajectory in mice with topical 11β-HSD1 inhibition, despite sustained oral glucocorticoid treatment and elevated serum corticosterone levels.

3) For diabetes, my Ph.D. student Dr Padiporn Limumpornpetch discovered 11β-HSD1 induction by hypoxia (a key element of chronic wounds), with restoration of vascular endothelial growth factor expression by 11β-HSD1 inhibition in primary human dermal fibroblasts. My current Academy of Medical Sciences Springboard Fellowship exploring diet-induced diabetes and delayed healing in 11β-HSD1 KO mice aims to shed further light on underlying mechanisms. Most importantly, my recent GC-SHEALD trial, which I led, found improved acute wound healing and epidermal integrity in patients with type 2 diabetes mellitus following oral 11β-HSD1 inhibitor AZD4017 treatment.

These discoveries are published in leading medical journals such as the Journal for Clinical Investigation, Journal of Investigative Dermatology, Endocrinology, and European Journal of Endocrinology.

In 2019 I was awarded the prestigious British Society for Endocrinology Early Career Prize in Translational Research.

Qualifications

• PhD Medicine
• BSc Biological Sciences

Professional memberships

• School of Medicine Research Ethics Committee
• STEM Ambassador
• Society for Investigative Dermatology
• Society for Endocrinology
• Endocrine Society

Student education

I am a tutor on several MBChB modules at Leeds and apply a research-led teaching approach, giving students the opportunity to analyse active research data (e.g. RNA-seq pathway analysis) and contribute to research publications. My translational research enables me to provide a rich learning experience, inspiring a high level of student engagement and performance. Examples of student feedback include “Ana is probably the best tutor because her feedback is so helpful”, “exceptional tutor”, “Ana was great, really helpful and supportive and useful to have someone who is a researcher themselves” and “Ana was brilliant. She provided appropriate amount of feedback, so we knew what we had to improve on”.

As an undergraduate final year FMH and FBS project supervisor, students have access to high-quality research models and methods, working with active research samples to generate publication-quality data. I aim to provide a high degree of autonomy, so students are inspired to develop their own research interests.

At a postgraduate level, I supervise Ph.D. students. Awarded projects include “ The Deleterious Effects of Glucocorticoids”, investigating the interplay between inflammation, hypoxia and cortisol metabolism in human skin.

I am also a registered STEM Ambassador and enjoy inspiring the next generation of scientists through mentorship on the Wellcome Broadening Horizons programme and University Mentoring Scheme.

Research groups and institutes

• Discovery and Translational Science
• Cardiometabolic
• Leeds Institute of Cardiovascular and Metabolic Medicine
• Musculoskeletal disease
• Translational and clinical research
• Dermato-Rheumatology Group

Projects

<li><a href="//phd.leeds.ac.uk/project/246-licamm-cellular-conversations:-stress-hormone-metabolism-as-a-novel-anti-fibrotic-target-in-giant-cell-arteritis">LICAMM Cellular conversations: stress hormone metabolism as a novel anti-fibrotic target in Giant Cell Arteritis</a></li> <li><a href="//phd.leeds.ac.uk/project/684-licamm-hypoxia,-inflammation-and-local-steroid-metabolism-during-wound-healing:-towards-a-new-therapy-for-diabetic-foot-ulcers">LICAMM Hypoxia, inflammation and local steroid metabolism during wound healing: towards a new therapy for diabetic foot ulcers</a></li> <li><a href="//phd.leeds.ac.uk/project/685-licamm-regulation-of-skin-function-and-wound-healing-by-pre-receptor-glucocorticoid-metabolism-in-diet-induced-animal-models-of-diabetes">LICAMM Regulation of skin function and wound healing by pre-receptor glucocorticoid metabolism in diet-induced animal models of diabetes</a></li>