Department of Medicine
Faculty Profiles by Division

Division of Rheumatology and Clinical Immunology

Faculty Profiles
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photo Robert Lafyatis, MD

Rheumatology

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
Biomedical Science Tower South, 7th Floor
Pittsburgh, PA 15261
Email: sadej@pitt.edu
Phone: 412-383-8734
Fax: 412-383-8753
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. More recently, we have applied single cell technologies to understand the molecular changes in stromal and inflammatory cell populations in the skin and lungs of patients with systemic sclerosis. In the skin we have discovered changes in several fibroblast populations. One of these populations, DPP4/SFRP2-expressing fibroblasts differentiate in two steps into myofibroblasts. In ongoing studies, we are identifying the alterations in chromatin structure and transcription factors regulating myofibroblast differentiation. We have carried out similar studies analyzing lungs from patients with systemic sclerosis associated interstitial lung disease. These lungs also show an emergent population of myofibroblasts, with an overlapping but distinct phenotype compared to skin myofibroblasts. We have also characterized a population of macrophages associated with progressive interstitial lung disease. We are further studying the pathways driving differentiation of both of these cell populations using single cell ATAC-seq. We anticipate that these detailed molecular understandings and in further in silico analysis in collaboration with colleagues in systems biology will lead us to better understand the cytokines communicating between cell populations promoting fibrosis, and lead to new key targets for therapeutic intervention.
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: Open chromatin and transcriptional regulation of dermal myofibroblasts in SSc
Role: Principal Investigator
Funding Agency: National Institute of Arthritis, Muscoskel, & Skin Disease
Grant Number: R61
Start Year: 2019
End Year: 2022
Title: Telomeres, Senescence, and Metabolism in AEC2
Role: Principal Investigator
Funding Agency: MedImmune, Inc.
Grant Number: CONTRACT
Start Year: 2019
End Year: 2021
Title: Translational Studies for Identifying and Targeting Novel Pathways in Systemic Sclerosis Pathogenesis
Role: Principal Investigator
Funding Agency: National Institute of Arthristis, Muscoskel, & Skin Disease
Grant Number: P50 AR060780
Start Year: 2017
End Year: 2022
Title: International Workshop on Scleroderma Research
Role: Principal Investigator
Funding Agency: National Institute of Arthristis, Muscoskel, & Skin Disease
Grant Number: R13 AR053784
Start Year: 2017
End Year: 2020
Title: Treatment of Periodontitis by Homing M2 Macrophages
Role: Co-Investigator
Funding Agency: National Institute of Dental Health
Grant Number: R01 DE029034
Start Year: 2020
End Year: 2025
Title: GATA6 in pulmonary arterial hypertension
Role: Co-Investigator
Funding Agency: Boston University / National Institute of Health
Grant Number: R01 HL150638
Start Year: 2020
End Year: 2024
Title: IDENTIFICATION OF PATHWAYS AND TARGETS IN POST-INFLUENZA INVASIVE PULMONARY ASPERGILLOSIS
Role: Co-Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R03 HL154242
Start Year: 2020
End Year: 2022
Title: Senescence and the validation of new therapeutic concepts for lung fibrosis
Role: Co-Investigator
Funding Agency: Boehringer Pharmaceuticals
Grant Number: CONTRACT
Start Year: 2020
End Year: 2021
Title: Proj 3 - Immunosuppression in Acute Lung Injury
Role: Co-Investigator
Funding Agency: Ohio State University/ National Heart, Lung, & Blood Institute
Grant Number: P01 HL114453
Start Year: 2019
End Year: 2024
Title: Type II Alveolar Redox Control in Fibrogenesis and Resolution
Role: Co-Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL149825
Start Year: 2019
End Year: 2023

Division Websites

Cardiology

Endocrinology and Metabolism

Gastroenterology, Hepatology and Nutrition

General Internal Medicine

Geriatric Medicine
Hematology/Oncology

Infectious Diseases

Pulmonary, Allergy and Critical Care Medicine

Renal-Electrolyte

Rheumatology and Clinical Immunology

Contact

Department of Medicine
1218 Scaife Hall
3550 Terrace Street
Pittsburgh, PA 15261
Email:  chairoff@pitt.edu
Phone:  412-648-9636
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