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Our rotation projects are in the area of diabetes and obesity, and we are interested in basic mechanisms of cell proliferation, differentiation and communication. Diabetes is highly correlated with obesity, but why obesity causes disease in some humans and not others is not understood. Amazingly, we still don’t understand how adipose tissue grows in human adults. A better understanding of this fascinating process can give us insight into basic mechanisms of cell growth, differentiation and communication, as well as mechanisms of disease, not only diabetes but also cancer and developmental defects. During your rotation, you will work on an important piece of a larger project, that has a well-defined outcome. Thus, your successful completion of the rotation project will allow you to be included at the time of publication of the work.
Project 1: Adipose tissue is not only formed by adipocytes, but by other cells such as endothelial, mural and immune cells. Also, there are multiple kinds of adipocytes with different functions. We have recently developed conditions to develop adipose tissue from humans in-vitro (adipose tissue “organoids”). From this tissue we have been able to separated single cells, and find that they grow into different kinds of clones. We are now conducting RNAseq on >300 of those clones, to determine how many cell types exist in human adipose tissue, and what their roles are. In this rotation, you will be able to analyze RNAseq data to define what genes characterize these cells, and you will use virus transduction to create immortalized cells for further study.
Project 2: Adipose tissue has many functions besides storing and releasing lipids. It also has to coordinate metabolism in the whole body. We have found that human “beige” adipose tissue, which is found in people who are metabolically healthy, expresses genes for secreted factors that communicate with the immune system and the brain. These include IL-33 and enkephalins. In this project you will knockout these genes, and investigate whether this changes the function of adipose tissue when we implant it into immune compromised mice.
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