Pathometabolism of Myeloid Cells

Myeloid cells are a group of innate immune cells, including monocytes, macrophages, granulocytes (neutrophils, basophils, eosinophils) and dendritic cells (DCs). Each of these subsets can be further divided into various functional subtypes depending on the specific tissue environmental cues during physiologic and pathologic conditions. Our group mainly focuses on myeloid cells in the context of tumor development and obesity-associated conditions.

Cellular metabolism enables immune cell differentiation and activation, by reprogramming itself to meet the energy demand or to provide building blocks for cellular processes. During the last 2 decades, striking discoveries have gradually emerged to demonstrate that metabolism of immune cells also possesses the power to govern effector functions of immune cells. Most importantly and intriguingly, some metabolic products (in other words, metabolites), are capable of modulating immune functions independent of energy supply or providing cellular building blocks. For instance, acetyl-CoA, α-ketoglutarate and lactate are able to control epigenetic regulation of gene expression, NO is able to regulate protein function via direct modification of target protein, and some other metabolites such as itaconate and succinate are capable of multiple actions either by direct modification of target proteins, or by competition with generic substrates of target enzymes, and even by activation of receptor-mediated signalings. Therefore, we believe it is high time to scrutinize cellular metabolites associated with pathologic conditions-triggered myeloid cell activation.

Specific aims:

1. To discover metabolites associated with pathologic conditions of certain human disorders /diseases.
2. To reveal the molecular mechanisms underlying the beneficial or deleterious roles of these metabolites