I am a tenured Professor in the School of Medicine at Case Western Reserve University. Since my graduate training my research has used genetically engineered mouse models to study the cellular and molecular processes critical for organ development and disease pathogenesis. As a graduate student, I focused my studies on neural plasticity and the role of neutrophin signaling in brain development and normal aging. As a post-doctoral fellow, my studies evolved to include the engineering of novel transgenic mice overexpressing angiopoietins or their receptor Tie2 to study their roles in the development of the vasculature, heart, liver, and skin. I established my independent lab in 2003, and since 2005 my research has focused on elucidating the pathogenic mechanisms underlying psoriasis skin inflammation and psoriatic disease co-morbidities, specifically cardiovascular disease (CVD) and arthritis. My approach is highly translational. We use transcriptomic and proteomic approaches to identify novel targets of interest in psoriasis patient skin (e.g. IL17C, KLK6) which then guide us in the creation of new original transgenic mouse models. We use these model systems to determine the pathogenic contributions of molecules-of-interest to skin inflammation and related co-morbidities, test novel intervention approaches, and then translate our findings back to psoriasis patients to validate our preclinical findings. Through this work I have become an expert in a diverse array of experimental approaches including mouse molecular genetics, phenotype characterization, cellular biology, RNAseq, proteomics, CyTOF and advanced bioinformatics.
Current research in the Ward lab is focused on identifying the cellular and molecular mechanisms underlying inflammatory skin disease and its associated co-morbidities, including atherosclerosis and thrombosis, arthritis, inflammatory bowel disease, and depression.
Our experimental approach utilizes a combination of in vivo mouse molecular genetics and in vitro cell culture methodologies. Using transgenic knockout and overexpression, CreLoxP and tetracycline based technologies we can modulate genes of interest in whole animals, in a tissue and cell specific manner, or in circulating blood cells only, providing us with an in vivo system ideal for studying the interactions between cells belonging to the nervous, musculoskeletal, vascular and immune systems. This work is further complemented and strengthened with in vitro experimental approaches using immortalized or primary cells from humans and mice coupled with established bioassays. We recently have embraced a Systems Biology approach for studying many of our biological questions. We regularly use CyTOF, multi-colour flow cytometry approaches, bulk RNASeq, Single cell Seq and other innovative approaches for studying how chronic skin-contained inflammation has the capacity to drive distant organ injury.
If interested in joining our group, please do not hesitate to reach out.
Our lab studies the cellular and molecular mechanisms mediating autoimmune disease with a focus on psoriasis, psoriatic arthrits and psoriasis comorbidities, including cardiovascular disease, inflammatory bowel disease, and depression. We combine novel mouse models of skin and inflammation with in vitro bioassays, experimental thrombosis models, and RNASeq, single cell RNASeq, CyTOF, and flow cytometry, along with standard cell biology assays to determine how chronic inflammation leads to systemic inflammation and distant organ injury. We translate our findings to psoriasis patients, and frequently develop new mouse models around new information identified in patient tissue and blood.
The lab has many projects that are ongoing including the following:
- understanding the cellular interactions that exist between nerves, blood vessels and leukocytes in order to identify the molecular mechanisms that sustain chronic inflammation;
- elucidating the cellular mechanisms by which the pro-inflammatory cytokine, IL-17C promotes and sustains chronic skin inflammation;
- actively seeking to identify the cellular events that explain why patients with chronic inflammatory disease, such as psoriasis are at increased risk for developing and dying of cardiovascular disease.
- using big data and multi'omics approaches (transcriptome, microbiome, metabolomic, proteomics)to identify psoriasis patient endotypes, and then overlay their data with similar data from our mouse models, then test hypotheses derived from these analyses to identify novel pathways, and unique endotypes that will respond to specific drugs. "Personalized Medicine" with the assistance of mouse models. We are using similar approaches to identify putative biomarkers of arthritis and ileitis. and
- Studying the contributions of KLK6 and PAR1 in promoting skin inflammation and identifying the cellular pathways linking skin-initiated inflammation with arthritis.
- Sun Pharma
- 1/1/2021 -12/31/2023 (PI: Ward)
- Project title: Use of the skin-specific KLK6+ transgenic psoriasis model to identify the cellular and molecular mechanisms mediating psoriatic arthritis.
- The goal of this award is to determine whether functional inhibition of IL-23p19 will improve the psoriatic-arthritis like phenotype in the Klk6+ mouse model.
- National Psoriasis Foundation
- 7/1/2020-6/30/2021 (co-PIs: Gudjonsson, Ward, Kahlenberg, Tsoi, and Maverakis)
- Project title: Driving Discovery towards Psoriasis Cure and Prevention
- The objectives of this project are to 1. identify high-risk groups for development of psoriasis and its comorbidities, 2. discover intrinsic mechanisms that inhibit and reverse psoriasis progression, and 3. determine autoantigen(s) and autoimmune disease mechanisms, with the overall goal to prevent psoriasis and its comorbidities.
- NIH-NIAMS Grant# R01 AR073196
- 07/2018-06/2023 (PI: Ward)
- Project title: Kallikrein-PAR interactions in skin inflammation.
- The goals of this project are to identify the mechanisms by which KLK6-PAR interactions promote skin inflammation and to translate our preclinical findings back to psoriasis patients.
- NIH-NIAMS Grant# P50 AR070590
- 09/2017-08/2022 (Co-PIs: Ward, Cooper, McCormick)
- Project title: Psoriasis Center of Research Translation
- The goals of this project are to advance translational discovery and application in psoriasis using a cutting-edge systems biology approach that integrates patient-centered data within a rich and synergistic /collaborative institutional environment.
- NIH-NIAMS Grant# R01 AR069071
- 2015-2021 (PI: Gudjonsson; Co-I sub-contract: Ward)
- Project title: Role of IL-13 and the IL-13 associated rs20541 risk allele in the pathogenesis of psoriasis
- The major goal of this project is to investigate the mechanism by which IL13 and the IL-13 associated risk variant influences the pathogenesis of psoriasis.