Nicole Ward, PhD

Professor
Department of Nutrition
School of Medicine
Professor
Department of Dermatology
School of Medicine
Professor
Department of Neurosciences
School of Medicine

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.

ResearchGate profile

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Research Information

Research Projects

The lab has many projects that are ongoing including the following:

  1. understanding the cellular interactions that exist between nerves, blood vessels and leukocytes in order to identify the molecular mechanisms that sustain chronic inflammation;
  2. elucidating the cellular mechanisms by which the pro-inflammatory cytokine, IL-17C promotes and sustains chronic skin inflammation;
  3. 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.
  4. 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
  5. Studying the contributions of KLK6 and PAR1 in promoting skin inflammation and identifying the cellular pathways linking skin-initiated inflammation with arthritis.

Recent Funding

  • 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.

Awards and Honors

Faculty Council Chair
2020
School of Medicine, Case Western Reserve University
Gilliam Memorial Lecture (cancelled due to COVID-19)
2020
Dept. Dermatology, UTSW
Research Achievement Award in Psoriasis
2019
American Skin Association
Eugene M. Farber Lecture
2016
Society for Investigative Dermatology
Collegiality Award
2012
Society for Investigative Dermatology
Research Career Development Award
2007
Dermatology Foundation
Research Scholar Award for Psoriasis and Inflammatory skin diseases
2007
American Skin Association
New Faculty Travel Fellowship
2005
Winter Conference on Brain Research
Doctoral Award
1998
Medical Research Council of Canada
Izaak Walton Killam Memorial Scholarship
1997
Scholarship in Teaching Award
2006
School of Medicine, Case Western Reserve University
Professor of the Committee Award (Neuromuscular Committee, Class of 2008)
2005
School of Medicine, Case Western Reserve University
Faculty Teaching Scholar
2004
Case Western Reserve University

External Appointments

Member
National Psoriasis Scientific Advisory Committee
2019
Board of Directors
International Society for Investigative Dermatology
2017
Member
Society for Investigative Dermatology Committee on Diversity and Inclusion
2016
Councilor (nominated position)
International Psoriasis Council (IPC)
2015
Board of Directors
Society for Investigative Dermatology
2017
Secretary-Treasurer
Society for Investigative Dermatology
2017
Editorial Board member
Journal of Investigative Dermatology
2011
Editorial Board member
Cytokine
2014
Editorial Board member
International Journal of Clinical and Experimental Pathology
2010

Publications

Education

PhD
Dalhousie University
Master of Science
Division of Health Sciences-Neuroscience
McMaster University
1996
Bachelor of Science
Biology/Psychology
University of Winnipeg
1995

Residencies, Internships and Fellowships

Post doctoral fellow, Dept. of Medical Biophysics and Molecular & Cell Biology
University of Toronto, Sunnybrook Research Center
2003
Post Doctoral Fellowship
Canadian Institutes of Health Research
2000
Post Doctoral Fellowship (Declined in lieu of another award)
Heart and Stroke Foundation of Ontario
2000