PhD Projects
The PhD in Biological Science (Stem Cell Biology) will be carried out under the supervision of a Principal Investigator (PI) from within the Cambridge Stem Cell Institute, and students will be based in their research group.
PhD supervision is available for 2027-28 entry in the labs below:
Group Leader: Dr Maria Alcolea (Alcolea Group)
Keywords: Mutant clonal competition, Early tumorigenesis, Squamous epithelia, Epithelial stem cells, Cell fate
Research Summary
Epithelial cells have the essential role of protecting us from external aggressions. However, this critical barrier must be able to adapt in order to face changes during developmental tissue formation and wound healing. A cut in our skin activates a number of cellular responses ensuring that the breach is fixed in few days, recovering the protective barrier. However, given that development and wound healing require the production of a significant amount of new tissue in a relatively short time, it is not surprising that cancer cells mimic these processes to rapidly produce a tumour mass. The difference being that tissue formation and wound repair are very controlled processes, while cancer is not. The Alcolea Group aims to investigate these adaptive cellular responses and the molecular mechanisms behind them in order to understand epithelial tissue behaviour, and how this can go awry during cancer development.
Research Focus
The Alcolea Group research interests have been focused on studying the behaviour of progenitor cells in the mouse oesophagus as a model to unveil the basic rules underlying squamous epithelial cell fate. Their work in the field has revealed how this tissue is maintained under homeostatic conditions, and how these rules switch upon injury.
More recently they have been able to identify how progenitor cells alter and adapt their behaviour in response to preneoplastic mutations, reflecting their remarkable cellular plasticity. Investigating the cellular and molecular mechanisms governing this dynamic behaviour and the potential implications for early cancer development will constitute the basis of my research programme.
To answer these questions, the group plans to make use of a combination of in vivo lineage tracing techniques, transcriptional network analysis, as well as 3D organoid and explant culture systems.
We encourage prospective PhD students to reach out directly to Dr Alcolea, mpa28@cam.ac.uk to discuss potential projects and supervision.
Group Leader: Dr Thorsten Boroviak (Boroviak Group)
Keywords: human embryo implantation, primate embryogenesis, implantation platforms, endometrium
Research Summary
The Boroviak lab focuses on how embryonic cells organise themselves to form the most complex lifeforms, such as human and non-human primates.
They follow primate embryonic cells through parts of their journey to provide insights into human development. Their approaches include simultaneous genetic and epigenetic high-throughput sequencing from single cells, embryonic stem cell culture and bioengineering of stem cell-based embryo models.
A deeper understanding of primate development is vital for innovative treatments of implantation failure, infertility and cancer as well as clinical applications of stem cell biology.
Research Focus:
Embryo implantation, gastrulation and organogenesis
The first signs of the human body axis can be traced back to the second week of gestation. To get to this point, the blastocyst implants and establishes a small sheet of cells, the embryonic disc. Deeply embedded within extraembryonic tissues, the embryo undergoes a reorganization process termed “gastrulation”, which transforms the embryonic disc into three germ layers and determines the entire future body plan.
Most knowledge on mammalian gastrulation is based on mouse, but human embryogenesis differs in anatomical architecture, timing, molecular configuration and sequence of cell-fate decisions. For instance, in human and non-human primates, the implanting epiblast polarises into a rosette, gives rise to amnion and forms a flat EmDisc. Rodent embryos form amnion later in development, after gastrulation.
Research goals
The central aim of the Group's research focuses on delineating the molecular crosstalk between the human embryonic disc and extraembryonic signalling centres, which control the sequence of cell-fate allocation in the primitive streak. To understand how these signalling centres emerge, we need to elucidate how extraembryonic lineages are specified in primate postimplantation development.
The Boroviak Group was the first to reveal the molecular landscape in primate embryos between implantation and gastrulation in vivo (Bergmann et al., Nature 2022). They developed epiblast- and amnion-spheroid cultures using microfluidics (Schindler et al., Stem Cell Reports 2021; Munger et al., Development 2022) and pioneered computational approaches, including spatial-identity-mapping, to determine the identity of in vitro cultured cells. Their ongoing work involves micropatterning, blastoids, microfluidics and bioprinting to emulate human and non-human primate development in stem cell-based embryo models.
The results from the work will be critical to understand human implantation failure, how errors in gastrulation can lead to congenital malformations and how germ layers are patterned for organ formation.
We encourage prospective PhD students to reach out directly to Dr Boroviak, teb45@cam.ac.uk to discuss potential projects and supervision.
Group Leader: Professor Cédric Ghevaert (Ghevaert Group)
Research Summary
Hospitals are currently entirely reliant on blood donors for the red cells and platelets transfusion administered to patients who are very anaemic or at high risk of bleeding. Producing these blood cells in the laboratory would take the pressure of the supply chain and would make finding compatible blood for patients with rare blood groups easier. The Ghevaert Group is developing novel methods to produce red cells and platelets from human stem cells by using key "identity switches" and programming the stem cells to become blood cells. This method generates highly pure cell harvest with large quantities of blood cells to the point that they are now setting up clinical trials to assess these cells in human volunteers.
Research Focus
The main focus of the Ghevaert group’s research is the production of blood cells for human use, namely red cells and platelets. They have developed a particular expertise in the production of these cell types from human pluripotent stem cells using methodologies that are compatible with the production of clinical grade products within the constraints of affordable manufacturing processes. To this end they are combining cellular programming through knowledge and manipulation of transcription factor networks and the creation of 3D biocompatible niches and bioreactors.
As a consultant haematologist for the NHS Blood and Transplant (a partner organisation of the University of Cambridge), Cedric has expertise recognised world-wide in carrying out first-in-man studies of manufactured blood cell survival and recovery in human volunteers. The RESTORE trial carried out in partnership with NHSBT, the Clinical Research Facility (Cambridge University NHS Foundation Trust) and Guy’s Hospital Radiopharmacy looks at survival of manufactured red cells post-transfusion is due to complete in 2024.
We encourage prospective PhD students to reach out directly to Professor Ghevaert, cg348@cam.ac.uk to discuss potential projects and supervision.
Group Leader: Professor Bertie Göttgens (Göttgens Group)
Research Summary
Blood stem cells maintain the lifelong production of all blood cell types. This depends on finely tuned control systems which can fail as we age or go wrong and lead to disease (leukaemia). The Göttgens Group uses experimental and computational approaches to discover how these control systems work and how their disruption leads to disease.
Research Focus
Combining experimental and computational approaches, the Göttgens group has mapped the gene regulatory networks that control blood stem cells and revealed how their disruption contributes to leukaemia. More recently, the group has harnessed single-cell and time-series genomics to build dynamic models of blood production, revealing how stem cells adapt during development, ageing and disease.
Current research focuses on:
(i) early blood development from pluripotent cells
(ii) mechanisms of cellular decision making in blood stem and progenitor cells
(iii) functional consequences of leukaemogenic mutations
(iv) computational modelling of normal and perturbed haematopoiesis
We encourage prospective PhD students to reach out directly to Professor Göttgens, bg200@cam.ac.uk to discuss potential projects and supervision.
Group Leader: Dr Chiara Herzog (Herzog Group)
Research Summary
Throughout life, our cells accumulate memories of their experiences, recorded on the “epigenome” - a layer of chemical tags on our DNA that switches genes on or off without changing the underlying genetic code itself. The Herzog lab studies one specific type of these chemical tags, called DNA methylation, which has been shown to change drastically with age, asks what it can tell us about the underlying processes of age-related disease formation. When and why does a cell become more vulnerable to age-related disease? Can we read these molecular annotations from a simple non-invasive test to catch that risk early, before a person ever falls ill? And can we actively rewrite these annotations to improve how stem cells function and age? We work across multiple tissues and stem cell systems to answer these questions, combining laboratory experiments with large-scale data analysis, with the ultimate aim of developing better tools for predicting and preventing age-related disease.
Age-related diseases emerge from the interplay of genetic background and accumulated biological experience. The epigenome, the layer of chemical modifications that regulates gene activity without altering the DNA sequence itself, integrates these signals, encoding the combined influence of genetic variation, environmental exposures, and cellular context into stable yet dynamic molecular patterns. At the same time, epigenetic states actively shape cell fate and tissue function, positioning the epigenome as both a molecular archive of biological history and a regulator of disease risk.
Research focus
The Herzog lab investigates how DNA methylation encodes these signals across diverse tissues and stem cell systems, and how this information can be harnessed to understand age-related disease, improve non-invasive risk prediction, and modulate stem cell function.
Research in the group is organised around three themes:
- Epigenetic memory and cellular ageing: Defining how DNA methylation captures and encodes biological experience, including ageing trajectories, environmental exposures, and cell-intrinsic history, across tissues and stem cells.
- Precision biomarkers of biological vulnerability: Translating epigenetic memory into non-invasive biomarkers that reflect vulnerability, resilience, and disease risk prior to clinical onset.
- Epigenetic regulation of stem cell function: Using experimental perturbation systems to determine whether epigenetic states causally influence stem cell behaviour and the ageing process.
We encourage prospective PhD students to reach out directly to Dr Herzog, ch2151@cam.ac.uk to discuss potential projects and supervision.
Group Leader: Professor Ragnhildur Thóra Káradóttir (Káradóttir Group)
Keywords: CNS, myelin, Oligodendrocyte, neuroscience, stem cells, brain, Multiple Sclerosis
Research Summary
For our brain to work, fast electrical communication between nerve cells is essential. This is achieved by insulating the nerves with a fatty substance called myelin. In diseases like multiple sclerosis, spinal cord injury and stroke, myelin is lost, while in cerebral palsy myelin fails to develop. Lack of myelin causes physical and mental disability. Myelin is provided by cells called oligodendrocytes, which develop from oligodendrocyte precursor cells (OPCs). In the adult, OPCs can repair myelin, but this repair often fails for reasons currently unknown. OPCs can also develop into other types of brain cell, including nerve cells, but it is not known what controls this choice of cell identity. The Káradóttir Group studies how OPCs generate myelin during development and in disease. By investigating how signals in the cells’ environment interact with the properties of the OPCs to instruct them to migrate, generate myelin-making oligodendrocytes, or develop into other brain cells. The aim of this work is to understand how OPCs decide to become myelinating cells, how they can be influenced to repair myelin in disease.
Research Focus
The CNS white matter links billions of neurons in the grey matter. Its function depends on oligodendrocytes enwrapping neuronal axons with myelin to synchronize and increase information flow between neurons: essential for our cognitive abilities, our perception of the world and our motor skills. The importance of myelin becomes evident in diseases, such as multiple sclerosis, where myelin damage leads to cognitive and motor disability. Unique to the CNS, myelin regeneration can occur spontaneously in demyelinating disease, as adult oligodendrocyte precursor cells (OPCs; a CNS stem cell that comprises 5% of all cells in the brain) respond to the demyelinating injury and differentiate into new myelinating oligodendrocytes. However, this process often fails, making OPCs differentiation an important therapeutic target.
The Káradóttir lab has previously shown that OPCs express neurotransmitter receptors and receive synaptic inputs from neuronal axons in the white matter, hence are capable of sensing changes in neuronal activity. The lab’s interest is to understand how signals from neurons induce OPCs to differentiate and myelinate axons during development and with normal ageing; this also could be an underlying mechanism for white matter plasticity.
The devastating consequences of dys/demyelination, in diseases like cerebral palsy, spinal cord injury and multiple sclerosis makes it important to study how OPCs differentiation is regulated. They are actively investigating how OPCs respond to myelin injury and whether neuronal activity and neurotransmitter signalling may regulate the myelin repair process. The lab’s ultimate aim is to find new treatments for white matter disease.
We encourage prospective PhD students to reach out directly to Professor Káradóttir, rk385@cam.ac.uk to discuss potential projects and supervision.
Group Leader: Professor Walid Khaled (Khaled Group)
Keywords: Tumour initiation, Cancer Prevention, lineage tracing
Research Summary
Over the last ten years, Professor Khaled has established an ambitious research programme focusing on studying the early cellular and molecular changes associated with tumour initiation. His lab’s ultimate aim is to translate these discoveries into novel cancer detection and prevention methods. He has been awarded several grants, including two competitive fellowships from CRUK - Career Establishment Award (2014-2021) and Programme Foundation Award (2021-2027). During this period, his lab made significant contributions to the field, some of which are highlighted below.
His contributions to the field include making all the sequencing data generated in the lab publicly available through easy-to-use websites. He also shares the lab’s protocols through his website and some cases through youtube videos (eg. single cell prep for the human breast cell atlas).
Based on their single cell work in mouse and human they have identified several pathways that are associated with precancerous cellular changes in the women at high risk of breast cancer. This includes the observation that immune cells in the healthy breast tissue from BRCA1/2 high risk women exhibit an exhausted phenotype. These dysfunctional immune cells are normally only found at latestage tumours. With further funding from CRUK they started a pre-clinical trial to assess the efficacy of these drug paving the way to window of opportunity trials in human.
We encourage prospective PhD students to reach out directly to Professor Khaled, wtk22@cam.ac.uk to discuss potential projects and supervision.
Group Leader: Professor Elisa Laurenti (Laurenti Group)
Research Summary
Every day a trillion blood cells are produced in our body. This amazing turnover is achieved thanks to blood stem cells. These cells have the unique capacity to produce all blood cells in healthy individuals but also after injury or infection. Their function is vital, because if impaired, either blood production fails or cancer arises. The Laurenti laboratory thus focuses on these 2 important questions:
- How are human blood stem cells different from other blood cell types?
- What is the impact of age and disease on human blood stem cell function? For this they measure human blood stem cell responses to a number of signals, compare them to other blood cells and identify specific genes that regulate their behaviour. We also study what goes wrong in blood stem cells when there is inflammation, in the elderly and during the early stages of cancer development. Understanding how blood formation occurs in humans in all of these contexts will help design new therapies against a range of diseases.
Research Focus
The human body makes one trillion blood cells per day. These include red blood cells, platelets and immune cells, which all provide vital physiological functions. Rare blood stem cells, also called haematopoietic stem cells (HSCs) are responsible for life-long blood production. Their function must be tightly regulated to continuously produce blood in accordance with the demands of our organism throughout our lifespan, while also ensuring recovery from infections and injuries. HSC are very different from all other blood cell types and have unique functional properties, such as their infrequent division and their capacity to give rise to all blood cell types. The Laurenti laboratory aims to understand blood formation throughout a human lifetime. The lab studies human HSC and progenitor cells using single cell biology techniques: functional single cell assays and single cell -omics technologies. The lab is currently investigating the unique molecular and functional properties of human HSC and progenitors across the human lifespan with a particular focus on ageing.
Another area of interest is the study of HSCs’ cellular and molecular responses to stress, with the goal to improve HSC ex vivo expansion and gene therapy protocols.
Understanding how the cellular and molecular composition of the HSC/ progenitor compartment changes in stress conditions and throughout a human lifetime has important implications for regenerative medicine and treatment of blood cancers.
We encourage prospective PhD students to reach out directly to Professor Laurenti, el422@cam.ac.uk to discuss potential projects and supervision.
Group Leader: Professor Sanjay Sinha (Sinha Group)
Research Summary
Blood vessel diseases cause heart attacks, strokes and aortic aneurysms (a ballooning then tearing of the main artery in the body). The Sinha Group uses human stem cells to generate smooth muscle cells, one of the main cell types that make up the blood vessel wall. If they use skin cells from patients with vascular diseases to make stem cells then the smooth muscle cells from those (induced) stem cells will have the same abnormalities as in the patient, thus providing a way to generate a "disease-in-a-dish". With these and other approaches they are trying to understand how blood vessels become diseased and trying to find new treatments for these diseases. They are also developing ways to transplant our stem cell generated cells to reverse the damage caused by a heart attack.
Research Focus
The Sinha lab’s overall aim is to develop new treatments for cardiovascular diseases, using their expertise in cardiovascular development, regeneration and disease modelling. They have pioneered the generation of embryonic lineage-specific vascular smooth muscle cells from human embryonic stem cells (hESC) and induced pluripotent stem cells, using chemically defined conditions. They have utilised this system to model genetically triggered aortopathies, such as Marfan and Loeys-Dietz syndromes. These “disease-in-a-dish” models are being used to understand the pathobiology of these conditions and to screen for new treatments.
Additionally, they are they are generating a detailed multiomic and spatial atlas of human heart development and modelling key developmental niches and events in vitro using hESC-based 3D system to define key regulatory mechanisms in humans.
Finally, they are testing the regenerative potential of hESC-derived epicardium and other cardiovascular cell types for heart repair after myocardial infarction, either through direct injection or in the form of an in vitro generated myocardial “patch”.
We encourage prospective PhD students to reach out directly to Professor Sinha, sinha@stemcells.cam.ac.uk to discuss potential projects and supervision.
Group Leader: Dr Mekayla Storer (Storer Group)
Research Summary
The life of a salamander is an enviable thing. If this animal loses a limb, it can just grow another one. Imagine if humans could do that. It’s not all bad news however. Mice and humans have retained a sliver of regenerative ability. If you damage the end of your finger, as long as there is a bit of nail left over and the wound is not stitched up, it will grow back. In the Storer lab, they are trying to understand why humans can regenerate a fingertip but not an entire arm. If they can understand how the tip of the finger regenerates, they can use this knowledge to develop therapies to regenerate other parts of the body.
Research Focus
The digit tip is the only part of the limb that can regenerate in mammals. The key step in this process is the formation of the blastema, a transiently proliferating cell mass that generates the different cell types of the digit to replicate the original structure. Therefore, understanding how the blastema forms and functions during digit tip regeneration will provide clues as to how they can stimulate regeneration of limbs and other tissues.
The Storer Group seeks to understand the cellular and molecular mechanisms necessary for blastema formation, and how these cells are co-ordinated temporally and spatially to regenerate the injured digit tip. Toward that end, they utilise in vitro blastema cultures, single-cell transcriptomic approaches and in vivo genetic lineage tracing studies.
We encourage prospective PhD students to reach out directly to Dr Storer, ms2786@cam.ac.uk to discuss potential projects and supervision.
Group Leader: Professor Sarah Teichmann (Teichmann Group)
Keywords: Spatial transcriptomics of the heart
Research Summary
The Teichmann lab strives to understand how humans are built from our most basic building blocks: our cells. They study how cells are different based on the genes they switch on, their physical location within our organs, how they communicate and how these things influence what they do. Understanding our cells not only allows us to understand how we ‘work’, but how things go wrong in disease and may provide new leads to improve human health. They have a particular interest in the immune system in health and disease. Many of our group are experts in data analysis, building new computational tools to drive our research, and that of the community, forwards. They are a key member of the Human Cell Atlas (HCA) project, of which Sarah Teichmann is co-chair. More information on the HCA can be found here.
Research Focus
Sarah Teichmann is one of the co-founders of the Human Cell Atlas, a global initiative bringing together thousands of scientists to ‘create a comprehensive reference map of the types and properties of all human cells, the fundamental unit of life, as a basis for understanding, diagnosing, monitoring and treating health and disease’ (HCA mission statement). The Teichmann Group studies the composition of human tissues in both healthy and disease states using single cell and spatial genomics, often using cutting-edge methods. Many of the group members have a deep interest in immunology, including tissue-resident immune cells and cross tissue studies. They study the healthy human immune system, how it develops during pregnancy, and how it is modified in disease.
The Teichmann Group is also world-leading in computational analysis and method development. The majority of their staff are ‘dry-lab’ scientists, working on data analysis, new methods and data portals.
Their greatest strength is their people. The members come from around the world and a myriad of different disciplines, working together to push scientific research and technology development. From those just starting out to world-leaders in their field, they are always looking for the best and the brightest to join the team.
We encourage prospective PhD students to reach out directly to Professor Teichmann, sat1003@cam.ac.uk to discuss potential projects and supervision.
Group Leader: Dr Richard Tyser (Tyser Group)
Keywords: Heart Development, Physiology
Research Summary
The heart is the first organ to form and function during embryogenesis, essential in providing the developing embryo with sufficient oxygen and nutrients. Congenital heart defects are the most common type of birth defect affecting almost 1 in 100 babies born in the UK.
Research in the Tyser Group explores how the mammalian heart begins to form and function during embryonic development. They use a combination of imaging and molecular based approaches to characterise cardiac progenitor cell populations, in both the human and mouse. Using this insight, they examine the mechanisms which regulate how cardiac progenitors differentiate to give rise to the functional beating heart. They are particularly focused on understanding how the onset of contraction influences heart morphology and cardiomyocyte differentiation.
As well as addressing questions of fundamental biological significance, the group’s research aims to augment therapeutic approaches to treat disease: by establishing the underlying causes of disease as well as providing a blueprint for regenerative strategies on how best to treat them.
We encourage prospective PhD students to reach out directly to Dr Tyser, rt593@cam.ac.uk to discuss potential projects and supervision.
Group Leader: Dr Konstantinos Tzelepis (Tzelepis Group)
Keywords: RNA biology, Epitranscriptomics, stem cells
Research Summary
Epitranscriptomics, the modulation of RNA function via its chemical modification, has emerged as a pervasive new mechanism of gene regulation. The role of the epitranscriptome on stem cell fate, maintenance and ageing remains largely unexplored. Similarly, the impact of aberrant RNA modification and editing on oncogenic transformation and cancer stem cell maintenance remains poorly investigated, however early studies suggest that the modification of RNA could be exploited for the development of new therapies for devastating diseases including anti-leukaemia therapies.
The Tzelepis group investigates the relevance of RNA modifications in normal and malignant stem cell biology, with a focus on haematopoiesis. Using sophisticated CRISPR screening platforms, the lab has identified a significant number of epitranscriptomic vulnerabilities of acute myeloid leukaemia (AML) and have gone on to investigate some of these in detail, including the m6A writer METTL3 (Barbieri et al, Nature, 2017) and the m7G writer METTL1 (Orellana et al, Mol Cell, 2021). Notably, their latest study of the first-in-class METTL3 inhibitor (Yankova et al, Nature, 2021) provides strong proof-of-concept that RNA-modifying enzymes represent a new avenue for anti-cancer therapeutics.
Future aims include study of selected RNA modifying enzymes which I identified as essential for either normal or leukaemic haematopoietic stem cells and whose function is currently unknown or incompletely understood with a particular focus on how particular RNA modifications regulate cell fate, differentiation, ageing and leukaemogenesis in normal and malignant haematopoiesis.
We encourage prospective PhD students to reach out directly to Dr Tzelepis, kt404@cam.ac.uk to discuss potential projects and supervision.
Group Leader: Professor George Vassiliou (Vassiliou Group)
Keywords: Clonal haematopoiesis, telomeres, leukaemia prevention
Research Summary
Each day humans produce more than 200 billion mature blood cells from a small number of blood stem cells, also known as haematopoietic stem cells (HSCs). HSCs are produced whilst we are still in the womb and, for the rest of our life, live in the bone marrow where the environment provides them with nutrients and signals to increase or decrease blood cell production as required by the body. However, like all cells, HSCs steadily accumulate random DNA mutations with time. Most mutations have no discernible effects, but a small minority can drive an HSC to divide and produce many copies (clones) of itself.This phenomenon, known as clonal haematopoiesis (CH), becomes very common with advancing age. Unfortunately, in some people CH progresses to a blood cancer like Acute Myeloid Leukaemia (AML) or Myelodysplastic Syndrome (MDS).
The Vassiliou Group investigates how these cancers develop, how they can identify people at risk of developing them and how they may be able to stop this from happening. In parallel, they explore how gene mutations make cells cancerous, apply genetic approaches to identify "weaknesses" of these cancerous cells and use these insights to develop new treatments against them.
Research Focus
The Vassiliou group seeks to understand the cell-autonomous and non-cell-autonomous processes involved in transformation of normal HSCs to leukaemic stem cells and to develop new therapeutic approaches to prevent and/or treat AML, MDS and related myeloid malignancies.
To achieve these aims, they use three main approaches:
- Application of genetic screens to identify and investigate genetic vulnerabilities of myeloid malignancies in order to develop new therapeutic approaches
- Generation and study of bespoke mouse models of somatic mutation drivers of myeloid malignancies, to define their molecular, genomic and phenotypic effects on haemopoietic stem and progenitor cells
- Investigation of the genetic, molecular and epidemiological basis of CH in healthy individuals, in order to predict and understand the drivers of leukaemic progression and develop new approaches for early detection and prevention of myeloid malignancies.
We encourage prospective PhD students to reach out directly to Professor Vassiliou, gsv20@cam.ac.uk to discuss potential projects and supervision.
Group Leader: Dr Adam Wilkinson (Wilkinson Group)
Research Summary
Haematopoietic stem cells (HSCs) are critical for human health and disease treatment. HSCs are a rare stem cell population that can generate all the cells of the blood and immune system. Many blood and immune cells are short-lived and must be continuously produced in huge numbers (~2 million per second) throughout our lives. Abnormalities in blood production are common and underlie a number of serious human diseases including blood cancers, anaemias and immunodeficiencies. Despite their importance, the paucity of HSCs and lack of tractable ex vivo HSC culture systems means that the mechanisms that regulate HSC activity are incompletely understood.
HSCs are also used in clinic therapy with HSC transplantation therapy currently represents the only curative treatment option for numerous haematological malignancies. Additionally, HSC-based gene therapies are being developed and used to correct various hereditary blood diseases. While potentially curative, these HSC transplantation therapies still represent a high-risk procedure and are not available to all patients. The Wilkinson Group are aiming to improve the safety, availability, and potential applications of HSC-based therapies through developing new tools to expand and modify HSCs ex vivo.
Towards this goal, they have pioneered new methods to expand transplantable HSCs long-term ex vivo (Wilkinson et al, Nature 2019; Igarashi et al, Blood Advances 2023; Sakurai et al, Nature 2023) and to evaluate the consequences of CRISPR/Cas9 gene editing on functional HSCs in transplantation models (Wilkinson et al, Nature Communications 2021; Becker et al, Cell Stem Cell 2023).
The Wilkinson laboratory is currently leveraging this technology to (1) investigate the molecular regulation of HSC self-renewal and lineage commitment, (2) better understand how HSC dysfunction can drive blood cancer initiation, and (3) develop novel HSC-based therapies.
We encourage prospective PhD students to reach out directly to Dr Wilkinson, acw63@cam.ac.uk to discuss potential projects and supervision.