Dr Monokesh Sen

CHARLES PERKINS CENTRE, THE UNIVERSITY OF SYDNEY, NSW

Dr Monokesh Sen is a researcher at the University of Sydney. Dr Sen completed a PhD at Western Sydney University, where a passion for neuroimmunology and MS research was sparked. He investigates neuroinflammation and demyelination, driven by a dedication to exploring new scientific frontiers and developing innovative research techniques.

About Dr Monokesh Sen

Tell us an interesting fact about yourself
Outside the lab, I find balance and inspiration through nature, travel, and exploration. Whether it's hiking through scenic trails, exploring national parks, or discovering new environments, being outdoors helps me disconnect from daily routines and reconnect with the natural world. These experiences not only allow me to recharge but often offer fresh perspectives that I carry back into my research. I'm also an avid gardener. At home, I cultivate a variety of vegetables, and I enjoy sharing the harvest with friends and neighbours. Gardening keeps me grounded and provides a daily reminder of the rhythms of nature - something that complements the analytical mindset required in scientific research. Together, these outdoor passions enrich my personal life and strengthen my sense of curiosity and well-being.
What inspired you to get involved in MS research?
My deep curiosity to uncover the root causes behind complex events has always driven me, both intellectually and geographically. This scientific curiosity led me to journey from Bangladesh to Australia in pursuit of advanced research opportunities. I was fortunate to receive exceptional mentorship during my PhD at Western Sydney University, as well as during post-PhD at the St. Vincent's Centre for Applied Medical Research and currently at the University of Sydney. These experiences, gained through collaborations with esteemed institutions and researchers, were instrumental in shaping my understanding of neuroimmunology and sparking my passion for MS research, laying a solid foundation for my future career as a researcher.
What do you think has been the most exciting development in MS research?
One of the most exciting recent advancements in MS research is the growing understanding of why remyelination often fails. Recent studies using gene knockout models have highlighted the pivotal role of microglia in promoting myelin repair. Microglia are now recognised as essential facilitators of remyelination, primarily through their ability to clear myelin debris via phagocytosis. This clearance process is critical, as the accumulation of damaged myelin inhibits the function and maturation of oligodendrocytes. By efficiently removing this inhibitory debris, microglia help to create a more permissive environment for oligodendrocyte activity and successful remyelination.
Tell us about your current research project
How macrophage-derived extracellular vesicles help repair myelin
This project will investigate the role of macrophage-derived extracellular vesicles (MEVs) in the remyelination process. To achieve this, we will first collect blood samples from individuals with progressive MS and healthy controls and then isolate peripheral blood mononuclear cells. We will then grow these cells in the lab and differentiate them into macrophages. These macrophages naturally release MEVs, which we will collect using ultracentrifugation. Next, we will administer MEVs intranasally to mice and investigate their biodistribution at the tissue and cellular levels. We will then test their effects in the cuprizone animal model of MS to explore how they influence oligodendrocytes and myelin repair. By understanding this process, we aim to discover new methods for repairing myelin and develop future treatments that may improve the lives of people with MS.
Why is your research important and how will it influence the understanding and treatment of MS?
While current treatments for MS primarily focus on suppressing autoimmunity and reducing inflammation, they do not effectively promote myelin repair. As a result, many individuals with MS continue to experience progressive neurodegeneration and irreversible disability despite treatment. This research aims to address this unmet need by investigating MEVs as potential mediators of remyelination. By exploring the regenerative properties of MEVs, this project has the potential to uncover novel therapeutic strategies that go beyond immune modulation and directly support myelin repair. Specifically, the study will advance our understanding of how MEVs: i) distribute within the mouse CNS and interact with oligodendrocytes; and ii) influence oligodendrocyte function and promote remyelination in vivo.
Tell us about your research project
The Role of Extracellular Vesicles in Multiple Sclerosis
This research focuses on investigating the role of macrophage-derived extracellular vesicles (MEVs) in remyelination. In MS, remyelination is often incomplete, and the underlying reasons are not fully understood. Activated microglia and macrophages are known to release signals that influence oligodendrocytes' function, but the precise mechanisms remain elusive. My research tests the hypothesis that microglia and macrophages support oligodendrocyte proliferation and maturation by releasing extracellular vesicles (EVs). These EVs are membrane-bound particles secreted by various mammalian cells, including microglia and macrophages. My research explores the role of MEVs derived from peripheral blood mononuclear cells of MS patients and healthy controls in modulating oligodendrocyte function. I am also investigating the proteomic and lipidomic profiles of MEVs from MS patients and healthy individuals.
Why is this research important and how will it influence the understanding and treatment of MS?
My research is significant in the context of MS and has both immediate and long-term implications. In the short term, it will focus on identifying protein and lipid changes within MEVs in MS. This study will also assess the effects of MEVs on oligodendrocyte function. These objectives will offer crucial insights into the lipidome and proteome profiles of MEVs from people with MS compared to healthy controls and their role in modulating remyelination. In the long term, my research holds the potential to identify protein- and lipid-based biomarkers for MS, which could serve as essential tools for monitoring and diagnosing MS and predicting treatment responses. Additionally, uncovering how MEVs regulate oligodendrocyte function and promote remyelination could lay the groundwork for developing new therapeutic strategies to treat MS.
What do you enjoy most about working in the lab and what are some of the challenges you face?
I am deeply passionate about working in the lab and tackling complex scientific challenges. The process of formulating hypotheses, designing experiments, and interpreting results constantly fuels my curiosity and drive for discovery. I particularly enjoy venturing into new areas of science and applying innovative techniques to push the boundaries of knowledge. Currently, my research into extracellular vesicles represents an exciting and forward-thinking direction in my scientific journey. These tiny yet powerful biological messengers hold immense potential for uncovering novel mechanisms in neuroinflammation and MS.

One of the persistent challenges in scientific research is securing adequate funding, which can often limit the scope and continuity of promising projects. I am incredibly grateful to MS Australia for awarding this Incubator Grant. This support is not only a significant milestone in my career but also allows us to investigate the role of extracellular vesicles in MS.
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Monokesh Sen