My research endeavours span from exploring the cellular mechanism of neurodegeneration to the broader implications of genetic diversity in disease modelling using iPSCs. In parallel, I am an advocate for greater representation and resources to harness Africa’s rich genetic diversity for neuroscience breakthroughs
iPSC Biobanking from Indigenous Africans for Neurodegenerative Research
The recent advancements in deriving brain cells from human-induced pluripotent stem cells (iPSCs) have offered novel insights into the mechanisms of neurodegenerative diseases and potential therapeutic avenues. This is primarily due to their capability to capture the genetic diversity of patient populations. iPSCs, which can be generated from skin biopsies using reprogramming factors, have the potential to differentiate into various brain cell types, including neurons, astrocytes, and microglia. However, the vast majority of existing iPSC lines come from European Ancestry populations, failing to adequately represent the extensive human genetic diversity. Given Africa’s rich genetic diversity and the current scarcity of iPSC models from African populations, our objective is to establish a biorepository of iPSC lines derived from indigenous Africans. This initiative aims to enhance cell and molecular investigations of neurological diseases and uncover the influence of African genetic backgrounds on these conditions, thereby elevating the contribution of African neuroscience on the global stage.
The Role of the Nucleolus in Neurodegenerative Diseases
Emerging research has spotlighted the nucleolus, a central hub for ribosomal RNA synthesis and assembly, as a pivotal player in diverse neurodegenerative diseases, including Huntington’s disease, Parkinson’s disease, and Alzheimer’s disease (AD). In AD, nucleolar alterations have been shown early in the disease, with associated downstream changes in the protein synthesis machinery. We have also shown that amyloid beta, which is a key player in AD, induces nucleolar stress and altered protein synthesis, suggesting this process may exacerbate AD progression. Our ongoing investigations further indicate pronounced nucleolar alterations in frontotemporal dementia cellular models. We aim to elucidate the role of the nucleolus in these diseases, paving the way for a comprehensive understanding of these diseases and how to target them
The Role of Tau in Health and Diseases
Tau protein is best known for its role in microtubule binding. However, our recent work and others showed it has multiple functions in non-microtubular locations, such as the nucleolus. Tau aggregation and spreading have been linked with neurodegeneration in many tauopathies. This is described as a gain of toxic function. Similarly, the loss of Tau’s normal function in brain cells has been suggested as the cause of Tau pathology in tauopathies. However, Tau’s normal role is far from being fully understood. We are interested in the mechanism of Tau toxicity, as well as developing a full understanding of the normal roles of Tau in the nucleolus. Our work will eventually contribute to elucidating the contribution of “gain of toxic function” or “loss of function” mechanisms in tauopathies.
African Neuroscience on a global stage
Africa has the world’s largest genetic diversity, which is critical for understanding human health. Yet, Africans are underrepresented in genetic studies. Africa’s research capacity is also weak, partly due to low funding and inadequate research infrastructure. For example, even though neurological disorders are significantly high in Africa, the overwhelming majority of research in this area is carried out in the Global North. We are interested in gaining accurate and in-depth information on African Neuroscience research. The data generated will help provide ideas on how African research can be strengthened.