Northwestern University

Feb
20
Tue 12:00 PM

BIDS Seminar: Deborah Winter, PhD - Faculty Research (Mapping the Gene Regulatory Networks of Macrophages in Rheumatoid Arthritis)

recurring see all events in this series

When: Tuesday, February 20, 2018
12:00 PM - 1:00 PM  

Where: Arthur Rubloff Building, Lakeview Conference Room (11th Floor), 750 N Lake Shore Dr, Chicago, IL 60611 map it

Audience: Faculty/Staff - Student - Post Docs/Docs - Graduate Students

Contact: Lindsay Varasteh   312.503.1997

Group: Center for Data Science and Informatics (CDSI)

Category: Lectures & Meetings

Description:

The Winter Lab of Functional Genomics applies genomic approaches to study the role of immune cells in health and disease.  In particular, we are interested in mapping the gene regulatory networks (GRNs) of macrophages through computational modeling of their transcriptional and epigenomic landscape in response to different environments, challenges, and disease.  Our previous work has shown that macrophages are capable of adapting their GRNs in response to signals from their tissue of residence through the combined action of cell-type-specific and tissue-specific transcription factors.  We believe this process represents a general mechanism by which macrophages exhibit plasticity in health and disease.  This talk will describe our work to analyze the transcriptional profile of macrophages in the joint synovium during the course of arthritis.  These synovial macrophages have been shown to derive from different sources (either tissue-resident or bone-marrow-derived) and play opposing roles in the onset and resolution of joint inflammation.  Using a mouse model of induced arthritis, we compare the transcriptional dynamics of different sub-populations of synovial macrophages during the course of inflammation.  These results suggest that different populations are pre-programmed in their response to arthritis.  In parallel, we isolate macrophages from synovial tissue of rheumatoid arthritis (RA) patients obtained through minimally invasive ultrasound-guided biopsy.  These samples provide us with the unique opportunity to profile in vivo synovial macrophages in patients with active RA.  We find that the global gene expression of macrophages clusters RA patients into 2 major groups associated with disease severity.  In addition, patients express different combinations of co-regulated gene modules, which may explain heterogeneity in disease progression and treatment response.  Our next step is to build on these studies to form a cohesive model of the function of synovial macrophage in arthritis and use these results to better predict the efficacy of different treatments.

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