Under homeostatic conditions, the bone marrow niche maintains a relatively hypoxic environment that is crucial for maintaining the hematopoietic stem cell (HSC) pool. Mesenchymal stromal cells (MSCs) are an important constituent of the bone marrow microenvironment and regulate the HSC fate either with the help of cell-cell contact or through a paracrine mechanism, through the secretion of various soluble and acellular factors. Previous studies have underlined the importance of in vitro hypoxic culture system in the maintenance of HSCs. Therefore, my focus of work is to understand how induction of hypoxia (chemically or physically) in MSCs affects the ex vivo cultured HSCs in a paracrine manner.
Neurodegenerative disease is a cause of progressive neuronal cell loss. As the lack of validated animal models makes it difficult to study neurodegeneration, the foremost objective of my study is to establish an effective in vitro neurodegenerative model system. Several studies have revealed the role of mesenchymal stromal cells (MSCs) and their secretome in rescuing neurodegeneration. Moreover, priming of MSCs to enhance their immunomodulatory function is a growing area of research. Hence the focus of my study is to evaluate the salutary effect of primed MSC secretome on the established neurodegenerative model system.
Efficacious ex vivo expansion of hematopoietic stem cells (HSCs) is a prerequisite for HSC transplantation in individuals with hematological disorders. Cytokine and HSC-supportive factors secreted by mesenchymal stromal cells (MSCs) are required for HSC growth and maintenance. Hence, MSCs are used in laboratories and clinics to improve the functionality of HSCs. The concern with this approach is that MSCs inevitably acquire a senescent phenotype after long-term ex vivo expansion, causing them to lose their HSC-supporting capacity. Hence the focus of my work is to rejuvenate ex vivo expanded MSCs with pharmacological compounds to enhance their HSC supportive functionality. I also aim to study the effect of secretome derived from such rejuvenated MSCs for ex vivo expansion of HSCs and enhancing their in vivo engraftment ability.
The traditional treatments for critical-sized bone defect repairs, such as autograft or allograft of bone, are expensive and face enormous challenges like donor availability and immune response. The success of MSC-based research approaches in improving bone regeneration is hindered not only due to the limited knowledge of therapeutic actions of MSCs but also due to challenges as well as expenses related to the cell production. Paracrine signaling effects of MSCs are facilitated through various soluble factors and extracellular vesicles (EVs)–collectively referred to as secretome – are responsible for their therapeutic effects. Thus, my research focuses on determining the osteoinducting potential of stem cell-secreted EVs utilizing various hydrogel-assisted 3D models. This approach could be used to build stem-cell free therapies for bone repair that circumvent the risks associated with current therapies.
Despite extensive research into the design of biomaterials for cartilage reconstruction, there is still a need for the development of materials that have sufficient mechanical conformity to work synergistically with healthy cartilage and subchondral bone while remaining soft enough to allow tissue incorporation. My research focuses on the development of effective and cost-effective biomaterials-based strategies for the treatment of damaged and diseased organs and tissues, with a particular emphasis on cartilage tissue regeneration. My work involves designing and synthesizing bioinspired biomaterials that mimic the native microenvironment and then assess the efficacy of these novel scaffolds for improved chondrogenesis.
Polycomb group proteins and other proteins catalyze various histone modifications to regulate gene expression, while other proteins remove these modifications. Our group and others have shown that H2AK119ub1 catalyzed by Polycomb Repressive Complex I (PRC1) plays a crucial role in gene regulation during neuronal lineage specification in human pluripotent stem cells. The H2AK119ub1 mark is erased by histone H2A deubiquitinases that counteract the gene repression by PRC1. There are only about nine are histone H2A deubiquitinases namely USP3, USP12, USP16, USP21, USP22, USP44, BAP1, MYSM1 and BRCC36 and there are only few reports of these in hematopoietic stem cells. However, there are no reports of histone H2A deubiquitinases in neuronal lineage specification from human pluripotent stem cells. I aim to study the expression of histone H2A deubiquitinases in during neuronal differentiation, as well as study the effects of shRNA-mediated knockdown of H2A- DUBs on neuronal differentiation.
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Ms Anushree Nandan (SIU JRF 2022)
B.Sc. (Biochemistry)
M.Sc. (Biological Sciences)
Research Interests: Role of Polycomb group (PcGs) proteins in regulating EMT genes in endometriosis
Project summary:
Endometriosis is a chronic disease of the female genital tract characterized by the presence of endometrial-like tissue outside the uterine cavity, which leads to complications such as severe pelvic pain and infertility. Current treatment strategies provide only symptomatic relief as its aetiology remains unclear. Polycomb group (PcG) proteins are histone modifiers that control the expression of genes involved in EMT and we speculate that their misregulation causes aberrant expression of EMT-related genes in endometriosis. Therefore, I aim to investigate whether PcG proteins occupy promoters of EMT- and fibrosis-associated genes in endometriotic tissue. The results of this study may help in identifying potential targets for treating endometriosis.