Dr Cristiano Scottà is currently a Lecturer in Biosciences at Brunel University and a Visiting Lecturer at King’s College London. His scientific career centres on translating immunological processes into clinical applications. At King’s College London, he initiated studies on preclinical models of cellular therapy, focusing on regulatory T cells (Tregs) to modulate inflammation in transplantation and autoimmune diseases. He developed novel strategies to ex vivo manipulate human Tregs for immunotolerance in solid organ transplantation, resulting in functionally stable and effective cell products. These approaches, along with his studies on human Treg biology, influenced the first clinical trials of Treg adoptive transfer in transplantation (ONE Study, Thril). His contributions expanded to five more clinical trials, spanning transplantation, aplastic anaemia, and IBD, involving the training of GMP operators and the design of GMP-compatible cellular therapy techniques. His research also explored approaches to improve the tissue localisation of therapeutic cell products. Cell trafficking to the gut was aided by studies on synthetic molecules targeting the retinoic acid pathway, leading to a clinical trial involving Treg adoptive transfer for Crohn’s disease. His studies also explored Treg interactions with other cell types. He investigated Tregs' role in reducing cholesterol accumulation in macrophages and stabilising atherosclerotic plaque, suggesting a positive impact in delaying atherosclerosis progression. Furthermore, he explored the genetic manipulation of human Tregs, designing CAR-Tregs to target allogeneic antigens and produce tolerogenic IL-10, with ongoing development of CAR molecules for therapeutic Tregs targeting either B cells or macrophages.
Project Overview
The Scottà group is seeking a highly motivated PhD candidate to join a pioneering research program at the intersection of adoptive cell therapy and maternal-foetal medicine. This project focuses on the development and validation of Chimeric Antigen Receptor (CAR) Regulatory T cell (Treg) therapies designed to mitigate the inflammatory damage associated with Gestational Diabetes Mellitus (GDM) and Preeclampsia.
A unique and critical focus of this study is the multicellular interaction within the placental microenvironment. Beyond studying blood vessel (endothelial) damage, the project will investigate how Tregs interact with maternal (decidual) and foetal (placental/Hofbauer) macrophages. In GDM, the balance between pro-inflammatory M1-like and anti-inflammatory M2-like macrophages is disrupted, leading to a feedback loop of inflammation that harms the placenta. This project will explore how Tregs, and specifically engineered CAR-Tregs, can act as "peacekeepers" to promote healthy macrophage polarization and protect vascular health, thereby preventing long-term cardiovascular issues for both mother and child.
Research Aims
- Engineering Precision: Develop novel CAR-Treg constructs designed to target activated antigen-presenting cells (APCs) or specific inflammatory markers in the placenta.
- Cellular Crosstalk Analysis: Use patient-derived samples to isolate and study the Treg-macrophage-endothelial axis. This includes analysing how Tregs influence the polarisation of maternal and foetal macrophages to restore a balanced immune environment.
- Advanced Validation: Utilise a cutting-edge "vasculature-on-a-chip" microfluidic model to observe real-time interactions and the efficacy of these therapies in a human-relevant system, replacing the need for animal models.
Training and Environment
The successful candidate will gain interdisciplinary expertise in:
- Advanced Immunology: CAR-Treg engineering, viral transduction, and multi-parameter flow cytometry
- Translational Medicine: Insights into clinical trial design and the translation of basic immunology into therapeutic strategies
- Bioengineering: Hands-on experience with microfluidic systems and 3D micro-physiological models for simulating human disease
Candidate Profile
We are looking for candidates with a strong background (BSc/MSc) in Immunology, Biotechnology, or Bioengineering. Experience in cell culture and molecular biology is highly desirable. You will work within a diverse and supportive team, benefiting from the mentorship of world-leading experts in immune tolerance.
How to apply
If you are interested in applying for the above PhD topic please follow the steps below:
- Contact the supervisor by email or phone to discuss your interest and find out if you would be suitable. Supervisor details can be found on this topic page. The supervisor will guide you in developing the topic-specific research proposal, which will form part of your application.
- Click on the "Apply here" button on this page and you will be taken to the relevant PhD course page, where you can apply using an online application.
- Complete the online application indicating your selected supervisor and include the research proposal for the topic you have selected.
Good luck!
This is a self-funded topic
Brunel offers a number of funding options to research students that help cover the cost of their tuition fees, contribute to living expenses or both. The UK Government is also offering Doctoral Student Loans for eligible students, and there is some funding available through the Research Councils. Many of our international students benefit from funding provided by their governments or employers. Brunel alumni enjoy tuition fee discounts of 15%.