Sally Cowley joined the Sir William Dunn School  of Pathology as a Wellcome Trust Career Re-Entry Fellow in 2007, engaged in a program of research into the differentiation of human Pluripotent Stem Cell-derived macrophages and their applications for HIV studies. With William James, she set up the James Martin Stem Cell Facility, affiliated to the Oxford Stem Cell Institute, for work with human Pluripotent Stem cells.

Collaborative projects she works on within this facility include:  iPSc-derived macrophages as a genetically-modifiable model system for understanding macrophage biology; developing iPSc-microglia to study the contribution of microglia to neurodegenerative disease; generating iPS cells from Parkinson’s Disease patients as part of a large scale Oxford Parkinson’s Disease Centre research programme funded by Parkinson’s UK; EU IMI StemBANCC, which established a panel of iPS derived cell lines from 500 patients as a platform for cellular phenotypic drug screening with industry partners; MRC DPUK Experimental Medicine Dementia Stem Cell Network, a UK-wide network (Oxford, Cambridge, UCL, Manchester, Cardiff, Edinburgh) using iPSc for modelling dementia.

Jane Vowles joined the Oxford University Dunn School of Pathology in 2010 as a research assistant generating iPS cells from Parkinson’s Disease patients as part of a large scale Oxford Parkinson’s Disease Centre research programme funded by Parkinson’s UK and then  StemBANCC project which established a panel of iPS derived cell lines from 500 patients as a platform for cellular phenotypic drug screening with industry partners.  She has also gained experience in Crispr Cas9 gene editing techniques.

She graduated in Agriculture from Reading University in 1981 and began her career working on reproductive physiology of ruminants at the Agricultural Production Research Unit at Reading.

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Dr Hazel Hall-Roberts (née Roberts) joined the lab in 2016, to research the role of microglia in Alzheimer’s disease. Microglia are immune cells that maintain a healthy brain environment by clearing up pathogens and ‘self’-made debris through a process called phagocytosis (‘cell eating’). Pathogens provoke a fuIl immune response, but ‘self’ debris usually does not. In an Alzheimer’s brain, microglial phagocytosis is impaired, and the microglia enter a state of chronic inflammation, in the absence of pathogens.  Hazel’s current project is jointly supervised by Dr Sally Cowley, and Dr Elena Di Daniel at the Alzheimer’s Research UK Oxford Drug Discovery Institute. Their main goal is to develop assays and tools for investigating microglial function in the context of Alzheimer’s disease, particularly their ability to clear neuronal debris via phagocytosis, using iPSC-derived macrophages as a cell model.

Hazel graduated from the University of Bristol in 2012 with a BSc in Biochemistry with Year in Industry, having spent a year working at GlaxoSmithKline Stevenage. At GlaxoSmithKline her research project looked at epigenetic proteins involved in the acute inflammation response of macrophages. This was followed by a PhD at the University of Bath (2012-16) with Professor David Brown, conducting research on α-synuclein, a protein that disrupts cell function in Parkinson’s disease, and how it promotes neuronal cell secretion of β-amyloid, a peptide that plays a key role in Alzheimer’s disease.

Alun is final year DPhil student on the Wellcome Trust Infection, Immunology, and Translational Medicine (IITM) doctoral programme. He started his journey into science doing a BSc Biomedical Sciences at UCL, from which he transferred to a BSc in Infection and Immunology for his final year. In this year he focussed his interests in infectious diseases onto virology, carrying out a dissertation project in the Tower’s lab working on new drug therapies for HIV-1 aiming to block interactions with host co-factors.

It was in the Tower’s lab that he first encountered and developed an interest in the Cyclophilins, a family of proteins with unclear functions and often found to interact with viruses. He wanted to see if they may be involved in the innate/antiviral immune response, but to achieve this he needed to knock out each family member. This ultimately led him to the James lab, where using their stem cell derived macrophages he has been able to explore the role of Cyclophilins in innate immunity and viral infections. During the course of his PhD, fortuitous observations have led him away from virology (much to his own disappointment) and he has become keenly interested in macrophage function and regulation in disease conditions

Dr. Sharat Warrier is a postdoctoral researched who joined the lab in 2018, to research the role of complement in Alzheimer´s disease.

Alzheimer’s disease (AD) is the most common contributor to dementia. It´s underlying mechanisms are complex, multifactorial, and incompletely understood. It has long been established that neuroinflammation and, more specifically, activation of the complement system, has an important role in pathological processes in AD brains. Complement composed of over 40 interacting proteins, is an ancient and powerful arm of the innate immune system, participating in the recognition, trafficking, elimination of pathogens and misfolded proteins, and maintaining homeostasis. In AD interest over complement stems from the recent large GWA studies which identified >25 genetic risk loci, including several complement associated genes. This is a collaborative industry funded project, jointly supervised by Dr. Sally Cowley at the James Martin Stem Cell Facility, Dr. Elena Di Daniel at the Alzheimer´s Research UK Oxford Drug Discovery Institute and Dr. Louis De Muynck at Janssen pharmaceutica in Belgium. The main goal is to understand the cell type in question for complement expression using iPSC derived cell types of the CNS and the role of the complement proteins in relation to progression of disease.

I am a DPhil student sponsored by the Oxford-E P Abraham Graduate Scholarship. My primary interest lies in the molecular pathology of Alzheimer’s disease. Currently, I am studying the processing of tau-protein aggregates by human iPSc-derived macrophages and microglia.  

My academic journey started with a detour in medicine. During the studies, however, I realized that the methods and medication available, particularly with regards to the diseases of the brain, can often leave doctors applying plasters to gunshot wounds. A search for real advancements in the way we treat brain disorders led me to science. I completed my neuroscience training at the King’s College London in 2018 with a year in Industry at the UCI MIND Institute in California, USA. There, under the mentorship and supervision from Prof Carl Cotman, I worked on several projects, including the investigation of IL12/23-induced modulation of synaptic plasticity, elucidation of effective exercise patterns for long-term memory formation, and targeting H3K9me3 for treatment of cognitive decline associated with ageing and Alzheimer’s disease. Our work on the effect of early-life exercise on late-life cognitive reserve received the Gold Award in STEM for Britain 2018.  

I finished my major in Biology with honours from the ESPOL Polytechnic University (Guayaquil – Ecuador) in 2014. During my undergraduate studies, I collaborated with the Antarctic Chilean Institute researching on genetic biomarkers of climate change and pollution using the Antarctic sea urchin (S. neumayeri) as a model. In 2015, I was awarded with a scholarship from the Ecuadorian National Government to conduct my MRes studies in Translational Neurology at UCL, where I joined Isaacs’ lab. My research consisted on the development of a biomarker for C9orf72 ALS/FTD. After obtaining a distinction degree, I was recruited as a Junior Lecturer/Researcher in the Faculty of Life Sciences (ESPOL). My field of research included biomarker analysis for novel nutritional therapies in neuropsychiatry disorders. I conducted one of the first pilot studies using the ketogenic diet as a treatment for schizophrenia and schizoaffective disorders in collaboration with Christopher Palmer, MD-PhD (McLean Hospital, Harvard Medical School). Currently, I remain holding the scholarship from the Ecuadorian National Government to conduct my DPhil studies at the Dunn School of Pathology, University of Oxford. 

RESEARCH AREA

My field of research is related to nutrient energy metabolism of the early human brain in health and disease. Currently, my DPhil research project is aiming to elucidate the connection between native immunity and metabolic dysregulation/shift in progenitor brain cells during Zika virus infection, as the cause of different brain abnormalities, particularly microcephaly.

Szymon is a DPhil student in Interdisciplinary Bioscience (BBSRC DTP in collaboration with Eli Lilly).  

Neurodegenerative diseases, especially Alzheimer’s and Parkinson’s, affect millions of people worldwide. Unfortunately, there has been little to no success in developing treatments to prevent the onset or slow the progress of these diseases. Inflammation within the central nervous system can affect the course of neurodegenerative diseases, but – at the moment – we lack a representative human in vitro system to suitably mirror the neuroinflammatory state. Induced Pluripotent Stem Cells (iPSCs) can be generated from human donor skin or blood cells and turned into different brain cell types.  

Szymon’s project will address the above limitation by culturing different human iPSC brain cell types together in a three-dimensional scaffold, including brain immune cells, microglia. This will enable us to study neuroinflammation and neurodegeneration ‘in a dish’.  Szymon graduated from The University of Nottingham (MSci Neuroscience). During his studies, he developed an interest in cell culture models by working on in vitro conditions which could promote stem cell characteristics in cancer cells (thanks to Dr Dr. Androutsellis-Theotokis). During a placement year at the Alzheimer’s Research UK Drug Discovery Institute at University College London, he was focusing on culturing primary rat microglia in serum free conditions (thanks to Dr Lorenza Magno). When finishing off the time in Nottingham, his MSci thesis indicated that a polygenic risk score generated from microglial genes can partly predict the risk of developing Alzheimer’s disease (thanks to Prof Kevin Morgan).