Dr Jon Hazeldine

Supervisor Details

Contact Details

j.hazeldine@bham.ac.uk

Institute of Inflammation and Ageing, University of Birmingham

Scientific Background

Research Interests

Dr Jon Hazeldine is a trained immunologist with a long-standing interest in how major trauma and thermal injury modulates the innate immune system.

His research is focussed primarily around understanding the mechanisms that underlie the immediate (<1 hour), acute (4-72 hours) and persistent (up to 1-year) state of systemic immuneparesis that develops in severely injured patients and its relationship with such clinical outcomes as sepsis and multiple organ dysfunction.

Research Themes

The effect of major trauma on innate immunity.
Mechanisms underlying trauma-induced immune suppression.
The immune and inflammatory response to thermal injury.
How the immune and inflammatory response to severe injury influences patient outcomes (e.g. development of sepsis).

Supervision Style

In three words or phrases: supportive, organised, detail-oriented.

Provision of Training

My training strategy revolves around me taking responsibility for your initial learning of the experimental techniques required for you to address the study objectives. When you are comfortable and competent in performing the experimental assays, you will be responsible for performing these independently.

Progression Monitoring and Management

I like to be kept up to date on my lab groups progress. To this end, weekly meetings will be held for study updates in order for me to see how work is progressing and for me to provide support/assistance/solutions for any experimental issues that have arose/are currently being experienced.

Communication

I like to hold weekly lab meetings to monitor the progress of studies. I am always contactable by e-mail to provide support if required. I prefer to hold face to face meetings rather than online meetings. Aside from myself, support will be provided by other experienced members of the lab group.

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 fortnight

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

Working Pattern

The timing of work in my lab is completely flexible, and (other than attending pre-arranged meetings), I expect students to manage their own time.

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:

Investigating the mechanisms that contribute to the state of systemic innate immune suppression in thermally-injured patients

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).

Investigating the mechanisms that contribute to the state of systemic innate immune suppression in thermally-injured patients

Secondary Supervisor(s): Dr Dhruv Parek

University of Registration: University of Birmingham

BBSRC Research Themes: Understanding the Rules of Life (Immunology)

Project Outline

With incidence rates as high as 65%, hospital-acquired infections (HAIs) are common secondary complications in patients that have suffered a major thermal injury. The immediate clinical and economic impact of HAIs are significant, with in-hospital mortality rates, length of hospital stay and inpatient costs all significantly higher in burns patients who develop HAIs. Strikingly, HAIs, and not the burn injury itself, are the leading cause of mortality amongst thermally-injured patients, with studies reporting 33-80% of deaths in burns patients result from HAIs. Thermal injury results in a state of systemic immune suppression, which precedes the development of HAIs. However, despite its clinical significance, the mechanisms responsible for post-burn immune suppression are poorly understood.

Previous work performed by our research group has shown that immune suppression develops immediately following thermal injury and persists for weeks and months. We found that when compared to healthy controls, key cells of the innate immune system, such as neutrophils and monocytes, exhibit impaired functional responses when challenged with pathogens. Examples of these immune impairments included significantly reduced phagocytosis and reactive oxygens species production by neutrophils challenged with Escherichia coli, impaired generation of neutrophil extracellular traps (NETs) and lower production of inflammatory cytokines by monocytes treated with the bacterial protein lipopolysaccharide (LPS). This immune suppression was evident in samples collected from patients on the day of injury and for up to 28 days post-burn. Impairments in multiple anti-microbial responses across different cell types point towards dysregulation in fundamental cellular processes rather than specific impairments in distinct signalling pathways in immune cells.

Immunometabolism is a term that describes the changes that occur in the metabolic pathways of immune cells upon their activation and is the process by which immune cells generate the energy they require to perform their anti-microbial functions. Interestingly, studies have shown that treating immune cells isolated from healthy volunteers with inhibitors of specific metabolic pathways reduces their functional responses. For example, inhibition of glycolysis, which is a metabolic pathway involved in the breakdown of glucose, has been shown to result in reduced NET production by neutrophils and pro-inflammatory cytokine production by LPS-challenged monocytes. As these functional defects mirror the features described for immune cells isolated from burns patients, then it plausible that major thermal injury results in dysregulated activation of metabolic pathways in neutrophils and monocytes. However, no study to date has investigated the impact of severe thermal injury on the metabolic profile of immune cells.

Objectives

The hypothesis of this study is that metabolic dysfunction results in immediate and sustained impairments in innate immune function post-burn. To investigate this, the study objectives are:

(1) To determine the impact that severe thermal injury has on the metabolic profiles of monocytes and neutrophils.

(2) Determine the effect that the circulating post-burn “microenvironment” has on the metabolic status of immune cells isolated from healthy volunteers.

Potential methods to be used

(1) The metabolic profiles of monocytes will be examined using SCENITH. This is a multiparametric high dimensional flow cytometry based technique that allows immunometabolic profiling at single-cell resolution.

(2) Neutrophil metabolism post-burn will be assessed using stable isotope-enriched nutrients and metabolic tracing. This analysis will involve gas chromatography-mass spectrometry (GC-MS) to analyse the incorporation of stable isotopes into cellular metabolic networks.

References

1. Hampson et al. PMID: 27232244.

2. Hazeldine et al. PMID: 38947312.