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Our lab is primarily focused on translational genomics research of inflammatory and autoimmune disease. We use sporadic cases, extreme phenotypes, and familial disease clusters to identify genetic risk factors. We assess the effect of genetic variation using molecular biology, cell line modeling, and bioinformatics. We use high-throughput technologies, such as single-cell RNA-Seq, to understand the molecular biology of disease severity.

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What do we currently research?

Hidradenitis suppurativa

A primary research focis of the lab hidradenitis suppurativa (HS), a chronic skin disease. The first outbreaks are usually during early adulthood, and result in the formation of multiple abscesses in apocrine gland-rich skin folds. This includes under the arms, beneath the breasts, and in the groin. The molecular etiology is not well understood despite a population prevalence of 1%.

Our current work is focused on understanding the role of gamma secretase in keratinocyte inflammatory responses and how rare PSTPIP1 variants impact inflammatory response in human immune cells.

We have collaborated on HS research with Drs. Milan Anadkat, Benjamin Kaffenberger, Jessica Kaffenberger, Brian Kirby, and Peter Nagele.

Autophagy in primary human mononuclear cells

Autophagy, specifically macroautophagy, is way for cells to digest old or damaged proteins and organelles. The process is used in immune response and also varies with age and in response to biological stimuli.

We are interested in identifying transcriptional biomarkers of autophagy by repressing and stimulating autophagy in primary human immune cells. We are using flow cytometry, bulk RNA-Seq, and single-cell RNA-Seq for this work.

Systemic sclerosis

Systemic sclerosis (SSc), also known in some forms as scleroderma, is a progressive disease with development of autoantibodies, (sometimes extensive) fibrosis, and vasculopathy. Some people with SSc have limited fibrosis and relatively little progression over time. Other people have extensive skin and internal organ fibrosis that increases in severity over time. There are few treatments available for SSc, and the available treatments often don’t work well for all patients. We believe that to develop better treatments we need to understand the molecular aspects of disease onset and progression.

Our current work in this area includes understanding the signals that cause reduced SPAG17 protein in SSc, how this alters signaling networks in human fibroblasts, and separately whether variants in complement genes predispose some with SSc to develop a thrombotic kidney crisis (scleroderma renal crisis).

We have worked with Drs. John Varga and Maria Teves in this area.

Rheumatoid arthritis and immune-related adverse event arthritis

Rheumatoid arthritis (RA) is a chronic and progressive immune-mediated joint disorder. Though joint pain and damage are main features, other tissues (such as the skin, heart, and blood vessels) can be damaged as well.

Immune-related adverse events (irAEs), including arthritis, are autoimmune or autoimmune-like disorders that occur after the treatment of cancer with an immune system checkpoint inhibitor. The treatment is intended to sensitive the immune system to the tumor, but sometimes leads to collateral damage.

Our current work in this area includes understanding the small RNA cargo of exosomes in the blood and joint fluid of individuals with RA. The goal is to determine whether any of these RNAs serve as severity or drug-response biomarkers, and whether the contents of exosomes can inform us of their cell type of origin. Other work includes determining whether irAE arthritis is like an “uncovering” of risk for RA or if it is a separate entity from RA entirely using single-cell RNA-Seq.

We have worked to obtain biological samples from patients and to purify exosomes with Drs. Christine Pham, Deborah Parks, and Wael Jarjour.

Genomics & Bioinformatics Core

We are part of a P30 funded core: the Rheumatic Diseases Resource-based Resource Center (RDRRC). Areas for focus:

If you are interested in discussing a project related to this cores services, please contact Eli directly after reading our standards for collaborations.

Jobs

If you are a student that wants to rotate in the lab, please contact Eli directly.

We have no salary funded staff positions open at this time.