Dr Rowan Hardy

Supervisor Details

Contact Details

School of Biosciences, University of Birmingham

Scientific Background

Research Interests

My research group is examining the roles of myeloid and mesenchymal steroid metabolism and signalling in mediating inflammatory disease pathophysiology and systemic complications in muscle and bone, identifying novel strategies to improve the safety profile of therapeutic glucocorticoids. This research involves world leading national and international collaboration across multiple centres of excellence at the UoB, including the MRC/Versus Arthritis Centre for Musculoskeletal Ageing Research (CMAR), and the Birmingham Biomedical Research Centre (BRC).

Research Groups

Inflammation and Ageing

Department of Metabolism and Systems Science

Supervision Style

In three words or phrases: Collaborative, supportive, spontaneous.

Provision of Training

I like to Train my students collaboratively across the Institutes that I work across to ensure a wide breadth of technical training and experience. However, I enjoy getting in the lab and supporting with training and experimental delivery when the opportunity arises.

Progression Monitoring and Management

I conduct weekly lab meetings within my research group where we focus on strategic experimental planning and shared problem solving. In addition, I always aim to maintain regular weekly one to one sessions to support personal research goals and career plans.

Communication

We generally communicate in person during the day or by email. We also have an informal WhatsApp group chat where we can reach each other in 'lab emergencies' or when social events are being planned.

PhD Students can expect scheduled meetings with me:

In a group meeting

At least once per week

In year 1 of PhD study

At least once per week

In year 2 of PhD study

At least once per week

In year 3 of PhD study

At least once per week

Meetings will mainly be face to face, and I am usually contactable for an instant response on every working day.

Working Pattern

Certain tasks in my lab need to occur at set times, and students need to be able to commit to a rota/timetable shared with other members of the team.

Notice Period for Feedback

I need at least 1 week's notice to provide feedback on written work of up to 5000 words.

MIBTP Project Details

Current Projects (2025-26)

Primary supervisor for:

Enhancing CD8+ T Cell Recruitment and Tumour Clearance via 11β-HSD1 Inhibition

See the PhD Opportunities section to see if this project is currently open for applications via MIBTP.

Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).

Enhancing CD8+ T Cell Recruitment and Tumour Clearance via 11β-HSD1 Inhibition

Secondary Supervisor(s): Dr Paul Foster

University of Registration: University of Birmingham

BBSRC Research Themes: Integrated Understanding of Health (Pharmaceuticals)

Project Outline

Triple-negative breast cancers (TNBC) are an aggressive subtype with limited therapeutic options, where chemotherapy remains the first-line treatment. However, TNBC demonstrates high levels of resistance and metastasis, leading to poor patient outcomes. In response to chemotherapy, tumour-associated macrophages (TAMs) play a critical role in shaping the tumour microenvironment. Initial inflammatory activation of these macrophages towards an M1-like pro-inflammatory phenotype supports tumour clearance secondary to recruitment and activation of cytotoxic CD8+ T cells. However, a progressive shift towards a tolerogenic M2-like pro-resolving state limits anti-tumour immunity and instead contributes to tumour chemotherapy resistance through secretion of growth factors and inhibition of cell death pathways.

Endogenous glucocorticoids (GCs), such as cortisol, promote tolerogenic M2-like macrophage polarisation in the tumour microenvironment. The enzyme 11β-hydroxysteroid dehydrogenase-type 1 (11β-HSD1) is a glucocorticoid activating enzyme that is upregulated in inflamed tumours. We have previously shown that it functions to amplify GCs signalling in macrophages and promotes M2-like macrophage polarisation in vivo. This project explores the selective inhibition of 11β-HSD1 during chemotherapy to block drug resistance mediated by tolerogenic M2-like polarisation, and enhance M1-like inflammatory macrophage CD8+ T cell tumour-clearance.

Therefore, we hypothesise that combining 11β-HSD1 inhibitors with chemotherapy will create a synergistic effect, boosting chemotherapy’s efficacy by increasing immune-mediated tumour clearance, and preventing tolerogenic macrophage mediated chemotherapy resistance. Thus, this approach represents a novel strategy for improving outcomes in TNBC.

Objectives

Investigate the role of 11β-HSD1 inhibition in modulating macrophage polarisation in the tumour microenvironment.
Assess the impact of 11β-HSD1 inhibition on CD8+ T cell recruitment, activation, and chemotherapy resistance in TNBC models.
Determine how 11β-HSD1 inhibition affects tumour burden, metastasis, and chemotherapy efficacy in preclinical TNBC models.

Methods

Co-culture modelling: We will study the polarisation of primary human macrophages in 2D and 3D (Matrigel) co-culture models with MDA-MB-231 cells treated with chemotherapy agents (paclitaxel, cisplatin). Macrophage polarisation will be assessed by cell sorting and mRNA analysis. Functional assays (cytokine profiles, efferocytosis) and tumour survival/proliferation assays will measure the effects of macrophage polarisation on tumour cells. The role of 11β-HSD1 will be studied using selective inhibitors.

Animal Models: MMTV-PyMT transgenic mice, crossed with 11β-HSD1 global and macrophage-specific knockout strains, will be used to study the effects of 11β-HSD1 inhibition on tumour progression. Mice will be treated with paclitaxel alone or in combination with 11β-HSD1 inhibitors, and tumour burden will be measured through electronic caliper measurements and histological analysis.

Flow Cytometry and Immunohistochemistry: Tumours will be analysed for macrophage polarization (M1 vs. M2) and CD8+ T cell recruitment using flow cytometry and immunohistochemistry to quantify key cytokines (e.g., CXCL9, CXCL10). PCR and immunoassays will assess the expression of chemokines, cytokines, and immune checkpoint markers critical to immune function.

Key References

Melo, P. et al. (2023). Inhibition of 11β-HSD1 Enhances Chemotherapy Efficacy in Breast Cancer. Journal of Experimental Oncology. PMID: 37028818.

Poinot, D. et al. (2024). Modulation of Macrophage Polarization by 11β-HSD1 Inhibitors in Immune Checkpoint Therapy. Nature Cancer. PMID: 38170044.