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Department of Medicine

Department of Medicine

  Division of Rheumatology and Clinical Immunology

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photo Robert Lafyatis, MD

Professor of Medicine

Email: lafyatis@pitt.edu

Phone: 412-383-8123

Contact
Office: 3500 Terrace Street
Room S720 BST
Pittsburgh, PA 15261
 
Phone: 412-383-8123
Fax:
E-mail: lafyatis@pitt.edu
Administrative Assistant:
Linda Sadej
Address: 3500 Terrace Street
S724A BST
Pittsburgh, PA 15261
Email: sadej@pitt.edu
Phone: 412-383-8123
Education and Training
Education
B.S., Life Sciences, Massachusetts Institute of Technology, 1978
B.S., Chemical Engineering, Massachusetts Institute of Technology, 1978
M.D., University of Cincinnati College of Medicine, 1983
Training
Residency/Intern, Medicine, NC Baptist Hospital, Bowman-Gray School of Medicine, 1986
Rheumatology Fellowship, National Institutes of Health, NIAMS, 1989
Biotechnology Fellowship, National Institutes of Health, NCI, 1990
Visiting Scientist, Institut Pasteur, France, 1991
Research Interest
Our laboratory effort is focused on understanding scleroderma (systemic sclerosis), and developing novel therapeutic approaches based on identifying biomarkers of the disease process and utilizing biomarkers in clinical trials. We have utilized a biomarker approach in a clinical trial of fresolimumab (anti-TGF-beta) to show a role for TGF-beta in skin fibrosis associated with systemic sclerosis. We are also applying our pharmacodynamic biomarker of skin disease to trials of tocilizumab (trial completed), and C-82 and rilonacept (ongoing). Our group has particular interest in understanding the mechanisms stimulating immune response in systemic sclerosis, focusing on innate immune responses leading to fibrosis and vascular injury. Our data show increased expression of interferon responsive genes in circulating monocytes of scleroderma patients, prompting current investigations into the stimulus for this pattern of gene expression and the effect of interferon on fibrosis and vascular injury. Most recently, we have been examining the transcriptome of single cells in the skin and lungs of patients with systemic sclerosis to better understand changes in gene expression in different immune and connective tissue cell types that lead to disease.

To aid in developing new therapies for systemic sclerosis, we are studying the pathogenesis through existing murine models, particularly bleomycin-induced skin and lung fibrosis, testing novel therapeutics to clarify the relationship between innate immunity and fibrosis. Our goal is to gain insight from these models that will enable us to propose more informative early phase clinical trials, utilizing biomarkers to show target engagement and as a surrogate clinical response.
Clinical Interest
Systemic Sclerosis, Systemic Lupus Erythematosus
Educational Interest
Mentoring Fellows, Residents and Graduate Students on Research Projects
Publications
For my complete bibliography, Click Here.
Selected Publications:
Stifano, G., Sornasse, T., Rice, L.M., Na, L., Chen-Harris, H., Khanna, D., Jahreis, A., Zhang, Y., Siegel, J., Lafyatis, R. Skin Gene Expression Is Prognostic for the Trajectory of Skin Disease in Patients With Diffuse Cutaneous Systemic Sclerosis. Arthritis Rheumatol. 2018; 70(6): 912-919.
Denton, C.P., Ong, V.H., Xu, S., Chen-Harris, H., Modrusan, Z., Lafyatis R., Khanna, D., Jahreis, A., Siegel, J., Sornasse, T. Therapeutic interleukin-6 blockade reverses transforming growth factor-beta pathway activation in dermal fibroblasts: insights from the faSScinate clinical trial in systemic sclerosis. Ann Rheum Dis. 2018; annrheumdis-2018-213031.
Fleury, M., Belkina, A.C., Proctor, E.A., Zammitti, C., Simms, R.W., Lauffenburger, D.A., Snyder-Cappione, J.E., Lafyatis, R., Dooms, H. Increased Expression and Modulated Regulatory Activity of Coinhibitory Receptors PD-1, TIGIT, and TIM-3 in Lymphocytes From Patients With Systemic Sclerosis. Arthritis Rheumatol. 2018; 70(4): 566-577.
Tabib, T., Morse, C., Wang, T., Chen, W., Lafyatis, R. SFRP2/DPP4 and FMO1/LSP1 Define Major Fibroblast Populations in Human Skin. J Invest Dermatol. 2018; 138(4): 139-146.
Sun, Z., Wang, T., Deng, K., Wang, X.F., Lafyatis, R., Ding, Y., Hu, M., Chen, W. DIMM-SC: a Dirichlet mixture model for clustering droplet-based single cell transcriptomic data. Bioinformatics. 2018; 34(1): 139-146.
Cascio, S., Medsger, T.A. Jr., Hawse, W.F., Watkins, S.C., Milcarek, C., Moreland, L.W., Lafyatis, R.A., Fuschiotti, P. 14-3-3z sequesters cytosolic T-bet, upregulating IL-13 levels in TC2 and CD8+ lymphocytes from patients with scleroderma. J Allergy Clin Immunol. 2017; S0091-6749(17): 31760-31768.
Lafyatis, R., Mantero, J.C., Gordon, J., Kishore, N., Carns, M., Dittrich, H., Spiera, R., Simms, R.W., Varga, J. Inhibition of ß-Catenin Signaling in the Skin Rescues Cutaneous Adipogenesis in Systemic Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial of C-82. J Invest Dermatol. 2017; 137(12): 2473-2483.
Derrett-Smith, E.C., Martyanov, V., Chighizola, C.B., Moinzadeh, P., Campochiaro, C., Khan, K., Wood, T.A., Meroni, P.L., Abraham, D.J., Ong, V.H., Lafyatis, R., Whitfield, M.L., Denton, C.P. Limited cutaneous systemic sclerosis skin demonstrates distinct molecular subsets separated by a cardiovascular development gene expression signature. Arthritis Res Ther. 2017; 19(1): 156.
Cao, L., Lafyatis, R., Burkly, L.C. Increased dermal collagen bundle alignment in systemic sclerosis is associated with a cell migration signature and role of Arhgdib in directed fibroblast migration on aligned ECMs. PLoS One. 2017; 12(6): e0180751.
Makino, K., Makino, T., Stawski, L., Mantero, J.C., Lafyatis, R., Simms, R., Trojanowska, M. Blockade of PDGF Receptors by Crenolanib Has Therapeutic Effect in Patient Fibroblasts and in Preclinical Models of Systemic Sclerosis. J Invest Dermatol. 2017; 137(8): 1671-1681.
Sponsored Research/Activities
Title: Single Cell Transcription of Dermal Mesenchymal Cells in Systemic Sclerosis
Role: Principal Investigator
Funding Agency: Scleroderma Foundation
Grant Number: RES
Start Year: 2017
End Year: 2019
Title: Dimethyl Fumarate in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension
Role: Principal Investigator
Funding Agency: National Institute of Arthristis, Muscoskel, & Skin Disease
Grant Number: R21 AR069285
Start Year: 2017
End Year: 2019
Title: 2017 ASPIRE
Role: Principal Investigator
Funding Agency: Pfizer Inc.
Start Year: 2017
End Year: 2019
Title: ELPIDERA Phase 1 Study: Testing Therapeutic Approach (ANTI-LOXL2) Efficacy in Murine Models of Systemic Sclerosis (SSc)
Role: Principal Investigator
Funding Agency: Moderna, Inc.
Grant Number: RES
Start Year: 2016
End Year: 2017
Title: Autoimmunity Center of Excellence Clinical Research Program
Role: Principal Investigator
Funding Agency: University of California - San Francisco/National Institute of Allergy & Infectious Diseases
Grant Number: UM1 AI110498
Start Year: 2015
End Year: 2019
Title: Innate Immunity in Dermal Fibrosis and Systemic Sclerosis
Role: Principal Investigator
Funding Agency: National Institute of Arthristis, Muscoskel, & Skin Disease
Grant Number: R01 AR051089
Start Year: 2015
End Year: 2017
Title: Rheumatic Diseases Research Core Centers (Admin Core)
Role: Principal Investigator
Funding Agency: Boston University
Grant Number: P30 AR061271
Start Year: 2015
End Year: 2017
Title: Novel Therapeutics and Precision Medicine in Systemic Sclerosis - (Admin Core)
Role: Principal Investigator
Funding Agency: Boston University
Grant Number: P50 AR060780
Start Year: 2015
End Year: 2016
Title: Single cell RNA sequencing and network analysis to identify the plelotropic effects of macitentan on scleroderma PAH patient-derived pro-inflmmatory monocytes
Role: Co-Principal Investigator
Funding Agency: Actelion Clinical Operations
Start Year: 2017
End Year: 2019