Research
Research focus
Myeloid cells including macrophages and dendritic cells (DCs) have long been hypothesized to be involved in driving disease progression as well as in disease resolution. For example, in steatotic liver disease (MASLD) macrophages are proposed to be one of the cell types driving progression from early stage disease (steatosis) towards more end stage disease called steatohepatitis. Thus, these cells are attractive targets for novel therapeutics whereby targeting/utilizing these cells could limit disease progression or promote repair and disease regression. However, myeloid cells in diseased/inflamed tissues are not homogeneous, rather they exist in many different subsets and/or activation states and therefore before we can think about generating new therapies using these cells, we first need to understand this heterogeneity and identify which subsets/states of these cells are appropriate therapeutic targets.
The overarching goal of the Scott lab is therefore to define the functional heterogeneity of macrophages and dendritic cells in tissues in the context of tissue damage and inflammation. We primarily focus on steatotic liver disease, tissue fibrosis and cancer. We aim to identify the different populations of these cells in different inflammatory contexts as well as to dissect the ontogeny and factors regulating the development of the different populations. Moreover, we strive to compare the myeloid cells across distinct disease settings to understand their broader relevance in disease. Finally, and perhaps most importantly, we want to understand the functionality of these different myeloid cell populations in inflammation and repair. We do this using a suite of genetic models allowing each population to be studied specifically. Ultimately, we hope that this information will allow us to utilize these cells therapeutically to help patients.
Our work to date has led to the identification of many different subsets and states of macrophages in the inflamed liver. Thus, in the different projects currently running, we are investigating the unique functional contributions of these cells while also examining DC heterogeneity and involvement in disease.