Research Areas

Understanding how changes in gene regulation influence aberrant cellular function is fundamental to deciphering the mechanisms of disease. The laboratory develops and applies computational graph-based methods of gene-regulation to immune cell populations in autoimmune conditions to better understand disease heterogeneity. These methods are applied to multiomics data and are further used to probe the effects of gene perturbations on cell-state in-silico.

We focus on applying Bayesian methods to elucidate regulatory interactions between genes. We characterize the attractor landscapes of immune populations and predict how these change under multi-gene perturbations. We also use systems biology methods, such as the integration of epigenetic and transcriptomic data to model transcriptional regulation. These allow for the identification of the transcriptional drivers of dysregulated pathways in disease and generate hypotheses that can be tested experimentally.

Scleroderma (SSc) is a multisystem autoimmune disease often presenting with devastating fibrotic complications such as SSc-associated Interstitial Lung Disease (SSc-ILD). We perform analysis of sequencing data from blood and spatial biology experiments of lung tissue, generously donated by our patients, to characterize and understand immune cell subtype contributions to disease. These are complemented by strong collaborations with cell biology laboratories to probe mechanisms. Following patients from the Kao Multispecialty Scleroderma Program longitudinally, we have a specific focus on the development of prognostic tools to predict and understand disease progression. We have ongoing projects on Monocytes and B-cells in SSc-ILD.

Rheumatoid arthritis (RA) is a systemic inflammatory disease that causes joint inflammation and destruction. We apply bioinformatics and systems biology methods to elucidate the diverse mechanisms of this disease. Our interests range from the epigenetic and transcriptomic analysis of fibroblast-like synoviocytes (which form the synovial lining and display a unique aggressive phenotype in RA) to investigating the role of transcriptional dysregulation in effector and regulatory T cell imbalance.