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Academic Background

Silvia Corvera is Professor of Molecular Medicine, director of the MD/PhD (MSTP) program, and director of the Clinical Translational Research Pathway. She holds the Endowed Chair in Diabetes Research.

She received her M.D. and MSc in Molecular Biology at the Universidad Nacional Autonoma de Mexico, and was awarded a Fogarty International Fellowship to conduct postdoctoral studies in the US. She was on the Faculty at the Department of Pathology at the University of Pennsylvania (1987-1990) before moving to the newly formed Program in Molecular Medicine at the University of Massachusetts Medical School.

Current Research

Metabolic diseases, such as type-2 diabetes, non-alcoholic fatty liver disease (NASH), and hypertension are an emerging worldwide epidemic associated with substantial human suffering and a large economic burden. We are interested in understanding the cellular and molecular mechanisms that underlie metabolic diseases, and enable therapeutic strategies to be developed.

We are specifically interested in human adipose tissue. Adipose tissue has amazing properties: each adipocyte can expand its size very rapidly, and is able to increase lipid storage 4-5 fold. In response to fasting, it rapidly releases this lipid to provide energy to the entire body. However, there seems to be a maximal capacity to expand, and when this capacity is reached adipocyte function fails. How the adipocyte can change its volume so dynamically is a very interesting cell biology question, and a very relevant one in understanding metabolic disease mechanisms. In fact, at similar weight, individuals whose adipose tissue is made up of many small adipocytes are at a lower risk of metabolic disease compared to individuals whose tissue contains fewer large adipocytes. Thus, one of our main interests is to understand the mechanisms that control the number and size of adipocytes.

Another amazing property of adipose tissue is its diversity of functions. We usually think of adipose tissue as a site for fat storage. However, a form of adipose tissue, called “brite” or “beige” in humans, is constantly burning fat to generate heat. “Brite/beige” adipose tissue is localized around the neck, close to major blood vessels, where the heat generated can serve to maintain core temperature. Humans who have more of this heat-generating adipose tissue tend to be lean and metabolically healthy, but what mechanisms underlie this correlation is not known. We have developed an approach to generate human “brite/beige” adipocytes in-vitro, and found that these cells can improve glucose metabolism when implanted into immune-compromised mice. A major goal now is to understand the mechanism for this effect, by discovering what factors stimulate the proliferation and differentiation of human brite/beige adipocytes, and whether these cells improve glucose metabolism through consumption of energy, through effects on other tissues, or both.

Another great unknown in the field of adipose tissue are the genetic factors that define its body pattern. Some individuals develop more adipose tissue under the skin in upper or lower extremities, while others have larger amounts in the abdominal region. These latter individuals are at a much higher risk of metabolic disease, even with little weight gain. We have developed an approach to generate adipose tissue “organoids”, starting from minute fragments of human adipose tissue that can be obtained through needle suction. These fragments can be induced to develop microvasculature and new adipocyte progenitors, which differentiate into functional adipocytes within a multicellular context. By studying the properties of adipose organoids generated from different body sites, and from individuals with differing body shapes, we hope to gain insight on the major determinants of human adipose tissue patterning.

Strong collaborations with clinical partners from the Departments of Surgery and OBGyN have allowed us to use human adipose tissue for our studies and determine how these are associated with diseases such as type 2 diabetes and gestational diabetes.

Rotation Projects

Rotation Projects

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.

One or more keywords matched the following items that are connected to Corvera, Silvia
Item TypeName
Academic Article Acute inhibition of insulin-stimulated glucose transport by the phosphatase inhibitor, okadaic acid.
Academic Article The vascular endothelium of the adipose tissue gives rise to both white and brown fat cells.
Academic Article Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone.
Academic Article Insulin stimulates the assembly of cytosolic clathrin onto adipocyte plasma membranes.
Academic Article Cidea is associated with lipid droplets and insulin sensitivity in humans.
Academic Article Enhanced angiogenesis in obesity and in response to PPARgamma activators through adipocyte VEGF and ANGPTL4 production.
Academic Article Depot-specific differences and insufficient subcutaneous adipose tissue angiogenesis in human obesity.
Academic Article Tensions rise and blood flows over dysfunctional fat.
Academic Article Effect of rosiglitazone on capillary density and angiogenesis in adipose tissue of normoglycaemic humans in a randomised controlled trial.
Concept Adipose Tissue, White
Concept Adipose Tissue
Concept Adipose Tissue, Brown
Academic Article Adipose tissue angiogenesis: impact on obesity and type-2 diabetes.
Academic Article Adipose tissue angiogenesis assay.
Academic Article Control of adipose tissue expandability in response to high fat diet by the insulin-like growth factor-binding protein-4.
Academic Article Alternatively Activated M2 Macrophages Improve Autologous Fat Graft Survival in a Mouse Model through Induction of Angiogenesis.
Academic Article Human adipose tissue expansion in pregnancy is impaired in gestational diabetes mellitus.
Academic Article Generation of Functional Human Adipose Tissue in Mice from Primed Progenitor Cells.
Academic Article Exercise Rescues Gene Pathways Involved in Vascular Expansion and Promotes Functional Angiogenesis in Subcutaneous White Adipose Tissue.
Academic Article Diverse repertoire of human adipocyte subtypes develops from transcriptionally distinct mesenchymal progenitor cells.
Academic Article PAPPA-mediated adipose tissue remodeling mitigates insulin resistance and protects against gestational diabetes in mice and humans.
Academic Article Adipocyte Heterogeneity Underlying Adipose Tissue Functions.
Concept Adipose Tissue, Beige
Academic Article Angiogenesis in adipose tissue and obesity.
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