3D Models of Health and Disease

We focus on engineering biomimetic models of multiple solid cancer types, including epithelial cancers and sarcomas. We aim to engineer the appropriate matrix composition, density and architecture and spatially segregate the cancer mass from the complex stroma. We can quantify invasion and interaction of the cancer into the engineered stroma.

Tumouroid models to study ameloblastoma action

Dr Deniz Bakkalci is developing 3D tumour models for ameloblastoma to understand molecular mechanisms behind ameloblastoma-induced bone resorption. She has been involved in research-based internships within the Northern Institute for Cancer Research and has completed a project on cytogenetic characterization of childhood Acute Myeloid Leukaemia (AML).

Renal tumouroids to predict patient response to therapies

Dr Katerina Stamati works on kidney and prostate cancer tumouroids. Her lab work has contributed to the optimisation of the methods to expand cells (cancer, supporting cells) from patient tumours. She has worked on a feasibility study of patient-derived tumouroids for personalised cancer treatment. She also focuses on understanding how the 3D environment affects drug responses and how increasing the complexity of the tumour microenvironment affects cells and therapeutic interventions.

Anuja Upadhyay is developing biomimetic collagen I based 3D in vitro models for fibrotic renal pathologies. Exploring cell-matrix interactions and changes in biomechanical properties using shear rheology, to determine the key players driving fibrotic remodeling in renal fibrosis and carcinomas. She is working in collaboration with UCB Pharmaceuticals to assess novel therapeutics using these platforms.

Low intensity ultrasound as therapeutics

Dr Pierre Gélat is investigating the biophysical effects of low-intensity ultrasound on 3D models of breast cancer. Ultrasound, best known in the context of medical imaging, has a growing number of therapeutic applications. These include thermal ablation of tumours at high levels and the stimulation of bone repair at lower levels. Low-intensity ultrasound stimulation is thought to trigger several force-sensitive cellular responses and mechanisms, resulting from micromechanical strains. A novel platform is being developed to characterize the mechanisms by which these effects occur.

Pancreatic cancer models

Dr Eirini Velliou is currently leading PANC-AID, an MRC-funded project which aims to develop a high fidelity pancreatic cancer model for patient & disease specific treatment optimization via robust control of various biochemical, biomechanical and biophysical features of the tumour (tissue) microenvironment. More specifically, tailoring in a controlled manner parameters of the tumour microenvironment like extracellular matrix composition, stiffness (at levels that realistically occur in PDAC in vivo), interstitial flow rates (mimicking high or low vascularisation or avascular tumours), vessel sizes or fibrotic levels (mimicking various density levels of the fibrotic reaction also known as desmoplasia, which is a hallmark of the disease) will enable the conduction of long term fundamental studies unravelling the interaction of each of those parameters with different cells of the tumour microenvironment. Underpinning such interactions at multiple levels, i.e., genetic, metabolic, will enable a better understanding of the evolution of the disease as well as the role of different tumour (tissue) microenvironment configurations on driving signalling pathways for migration and metastasis. Furthermore, such a robust, tuneable, representative model for pancreatic cancer will help improve the success rate of emerging therapies and constitute a platform for personalised medicine.

Annie Kataki is working on developing a biomimetic 3D model of pancreatic cancer for screening novel radiotherapy approaches, e.g., proton therapy. She is exploring the role of cellular, architectural, and biochemical components of the model on the response to X-rays and protons, aiming at designing a low-cost high-throughput tool for personalised radiotherapy screening.

Dr. Priyanka Gupta is working towards developing an advanced biomimetic 3D in vitro model of pancreatic cancer for therapeutic assessment (Research Project: https://gtr.ukri.org/projects?ref=MR%2FV028553%2F1). Her work is focused on incorporating cellular, architectural and biochemical complexities within the model to support animal-free cancer research.

Kyle Saunders is developing methods for analyzing the lipid contents of living single cells by utilising nanocapillary sampling coupled to live cell imaging. Specifically, he is monitoring the response of pancreatic cancer cells to proton beam irradiation, including the behaviour of their lipid droplets and changes to the lipidomic profile.

Breast cancer models

Salma Galal aims to develop a biomimetic 3D tumor model that closely recapitulates breast tumor microenvironment in vivo by incorporation of stromal cells such as endothelial cells, mesenchymal stem cells, etc. Then, investigate nanoparticles as drug delivery systems for cytotoxic chemotherapeutic agents and their effect on 3D breast tumor model.

We combine clinically relevant 3D cancer models such as patient derived explants (PDEs), with spatial multiomics endpoints, to interrogate their suitability for drug development & personalised medicine.

Radio3D

Dr. Uzoamaka Okoli is a Research Fellow working on the PCUK-funded project RADIO3D, led by Dr Susan Heavey. Dr Okoli covers the preclinical work packages under this project, involving patient-derived explant establishment, in vitro models, and spatial transcriptomics. She is also involved in other related spatial omics, cancer disparities, and 3D model projects in Heavey Lab. She works closely with clinical members of the team to ensure her work is clinically relevant. Dr Okoli has a PhD in Pharmacology and Therapeutics from the College of Medicine, University of Nigeria, where she has developed preclinical tools such as breast cancer PDX models and Lectures.

Urological models

Dr Dechao Feng endeavours to characterize prostate patients receiving radiotherapy and link the treatment efficiency to genetic and biological drivers through clinical informatics and bioinformatic analysis.

Lung cancer prevention

Andrei Enica (MRC-funded PhD student) is focusing on how spatial multiomics can inform the prevention of lung cancer. His work involves understanding the immune system during cancer development, a context in which spatial information is crucial. Requiring both wet lab and extensive computational work, Andrei is jointly supervised by Dr James Reading (UCL Cancer Institute) and Dr Susan Heavey (Centre for 3D Models of Health and Disease).

Prostate patient derived explants

Vithurran Thavarajah is replicating features of prostate cancer in vitro. Using different endpoint analyses including spatial omics to characterise the effects of in vitro culture conditions on aspects of prostate cancer biology in patient-derived explant models. Characterisation includes tissue morphology, biological pathways, cell-cell interactions and viability.

Gioblastoma 3D models

Bow is primarily working in the Centre of Targeted Cancer Therapies and closely collaborating with the Centre for 3D Models of Health and Disease. She is working on a pipeline to understand the uptake of nano-drugs in 3D constructs, towards understanding the mechanisms of nanoparticle enhanced radiotherapy

We develop 3D biomimetic in vitro collagen tissue models that mimic the structural and mechanical properties of native tissues. We are using these models to study cell-matrix interactions of healthy and hernia fibroblasts and to perform pre-clinical testing of commercial surgical meshes. We also develop inexpensive approaches for healthcare problems, such as an affordable, biomimetic surgical mesh for abdominal wall repair. We correlate the biological behaviour of cells to biomechanical properties of native tissues and engineered materials.

Development of a novel mesh for abdominal wall repair

PhD student Alessandra Grillo (supervisors: Dr Kureshi, Prof. Mudera) is developing a new biocompatible mesh for abdominal wall repair, combining synthetic and natural components. She worked on the use of biomaterials for drug delivery to treat peripheral nerve injury as part of her MSc project.

Pre-clinical hernia mesh testing

Tom Whitehead-Clarke is investigating pre-clinical hernia mesh testing. His project uses a 3D tissue model of the human rectus sheath to test several commercially available hernia meshes, with the aim of setting a gold-standard in the field of pre-clinical mesh testing. Tom is a specialty registrar in general surgery with interests in upper gastrointestinal surgery and complex hernia surgery.

Research in this area focuses on engineering specific elements of the stem cell niche. We have engineered several aspects of the stem cell niche, including the appropriate cytokine environment, the matrix composition and stiffness, and the effects of physiological hypoxia on stem cell populations.

Improving tissue integration and scaffold survival

Jasmine Ho (MRC and Rosetrees Trust funded PhD) is researching how to improve new blood vessel formation and growth in tissue engineered scaffold during the initial crucial stages of implantation. She will apply this knowledge towards improving tissue integration and survival of TE scaffolds in vivo. Her research shows that cells, particularly mesenchymal stromal/stem cells, when placed in a low oxygen environment, accelerate the growth of new blood vessels. She is looking to optimise the ideal oxygen conditions to yield the best pro-angiogenic environment without compromising cell viability. The findings will benefit tissue-engineered organ transplantation, organ regeneration and wound healing.

Engineering the hierarchical structure of skeletal muscle using 3D-bioprinting: clinical and food security applications

This is a collaboration with Prof. Kaushik Chatterjee at the Indian Insitute of Science, where we aim to 3D-bioprint skeletal muscle that accounts for the structure and scale of in vivo tissue. In this regard, the work will contribute towards the development of tissue implants in trauma and disease applications, as well as for lab-grown meat.

An integrative investigation into the role of muscle regeneration in total knee arthroplasty outcomes  

Skeletal muscle strength and function directly impacts outcomes following total knee arthroplasty. How muscle regenerates following this intervention and the impact of this on patient outcomes, is currently not known. This project is a collaboration with colleagues (PhD Student: Abderrahmane Boukabache) at the All India Insitute of Medical Sciences, where we aim to investigate muscle regeneration following TKA using a novel integrative approach.

Understanding the nutritional requirements for lab-grown meat

This is a project in collaboration with Dr. Adrian Slee and Brittany Cucchiaro (Division of Medicine) to develop a specification for the nutritional requirements for lab-grown meat. This is to ensure that research and development can focus on ensuring that any products meet nutritional and health standards.

Dr Eirini Velliou is leading activities on the development of 3D models for microbiological studies. More specifically, her microbiology work involves the design of biochemically, structurally and rheologically complex 3D multi-phase structures for studying the formulation and communication of bacterial communities, i.e., biofilms, of pathogens and natural microflora. Furthermore, she is looking at the response and potential stress adaptation of such communities to novel (non-thermal) microbial inactivation approaches such as Plasma, Ultrasounds and natural antimicrobial compounds.

Biochemically complex viscoelastic 3D models for studying the growth and spatial distribution of pathogenic bacteria

Lisa Purk is working on the development of biochemically complex viscoelastic 3D models, for studying the growth and spatial distribution of pathogenic bacteria. Her models are multiphasic, containing polysaccharides, proteins and fat. They are used for single cultures and co-cultures to study strain-strain spatial interactions. Furthermore, she uses the models for the development and application of novel mild preservation strategies.

Developing novel sustainable processing control strategies for monitoring bacterial pathogens

Melina Kitsiou is working on developing novel sustainable processing control strategies for monitoring bacterial pathogens. She is studying the antimicrobial efficacy of non-thermal technologies and natural antimicrobials utilizing 3D in vitro models. These models enable tuneable control of the biochemical, biomechanical and structural environment, as compared to industrial (food) products.

Wearable strain sensor applied for smart electronic skin

Wenqing is working on developing a novel wearable strain sensor applied for smart electronic skin and potential wound dressing. She is focused on investigating the mechanical strength of polymer based cross-linked hydrogels, films and printed matrix. Subsequently, she is exploring their anti-bacterial properties and environmental tolerance, with the benefits of facilitating the prediction of expected healing time.