Robert Lafyatis, MD

Research Interests

Dr. Lafyatis overall research interest is to better understand the pathogenesis of systemic sclerosis, and its skin and pulmonary complications. He studies both mesenchymal and inflammatory cell types in these tissues. Currently the major laboratory focus is using single cell RNA-sequencing on skin and lung tissues. This technology is enabling his group to characterize altered genes expressed by the mesenchymal and inflammatory cell types involved in pathogenesis of these diseases. These observations are leading to several hypotheses regarding specific genes and cell types promoting lung and skin fibrosis. The laboratory is particularly studying macrophages and the profibrotic factors driving specific macrophage cell types. His laboratory is also studying the mediators produced by macrophages that activate fibroblasts to become myofibroblasts.

In addition to translational studies, Dr. Lafyatis has developed a series of mRNA biomarkers of skin disease severity in patients with systemic sclerosis. His laboratory and clinical staff are studying the effect of therapeutics on these biomarkers, as a way to assess drug efficacy and to understand the role of pathways blocked by these therapeutics in the disease pathogenesis. Ongoing studies will use single cell RNA-sequencing as the next step in this work, providing insights into how therapeutics affect each of the cell types involved in skin disease pathogenesis.

 

Selected Publications

  • Lafyatis R, Mantero JC, Gordon J, Kishore N, Carns M, Dittrich H, Spiera R, Simms RW, Varga J. Inhibition of beta-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. doi: 10.1016/j.jid.2017.06.032. PubMed PMID: 28807667.
  • Man A, Correa JK, Ziemek J, Simms RW, Felson DT, Lafyatis R. Development and validation of a patient-reported outcome instrument for skin involvement in patients with systemic sclerosis. Ann Rheum Dis. 2017;76(8):1374-80. doi: 10.1136/annrheumdis-2016-210534. PubMed PMID: 28213563.
  • Rice LM, Mantero JC, Stifano G, Ziemek J, Simms RW, Gordon J, Domsic R, Lafyatis R. A Proteome-Derived Longitudinal Pharmacodynamic Biomarker for Diffuse Systemic Sclerosis Skin. J Invest Dermatol. 2017;137(1):62-70. doi: 10.1016/j.jid.2016.08.027. PubMed PMID: 27640094.
  • Nazari B, Rice LM, Stifano G, Barron AM, Wang YM, Korndorf T, Lee J, Bhawan J, Lafyatis R, Browning JL. Altered Dermal Fibroblasts in Systemic Sclerosis Display Podoplanin and CD90. Am J Pathol. 2016;186(10):2650-64. doi: 10.1016/j.ajpath.2016.06.020. PubMed PMID: 27565038; PubMed Central PMCID: PMC5222985.
  • Christmann RB, Wooten A, Sampaio-Barros P, Borges CL, Carvalho CR, Kairalla RA, Feghali-Bostwick C, Ziemek J, Mei Y, Goummih S, Tan J, Alvarez D, Kass DJ, Rojas M, de Mattos TL, Parra E, Stifano G, Capelozzi VL, Simms RW, Lafyatis R. miR-155 in the progression of lung fibrosis in systemic sclerosis. Arthritis Res Ther. 2016;18(1):155. doi: 10.1186/s13075-016-1054-6. PubMed PMID: 27377409; PubMed Central PMCID: PMC4932708.
  • Rice LM, Ziemek J, Stratton EA, McLaughlin SR, Padilla CM, Mathes AL, Christmann RB, Stifano G, Browning JL, Whitfield ML, Spiera RF, Gordon JK, Simms RW, Zhang Y, Lafyatis R. A longitudinal biomarker for the extent of skin disease in patients with diffuse cutaneous systemic sclerosis. Arthritis Rheumatol. 2015;67(11):3004-15. doi: 10.1002/art.39287. PubMed PMID: 26240058; PubMed Central PMCID: PMC5522178.
  • Rice LM, Padilla CM, McLaughlin SR, Mathes A, Ziemek J, Goummih S, Nakerakanti S, York M, Farina G, Whitfield ML, Spiera RF, Christmann RB, Gordon JK, Weinberg J, Simms RW, Lafyatis R. Fresolimumab treatment decreases biomarkers and improves clinical symptoms in systemic sclerosis patients. J Clin Invest. 2015;125(7):2795-807. doi: 10.1172/JCI77958. PubMed PMID: 26098215; PubMed Central PMCID: PMC4563675.
  • Christmann RB, Sampaio-Barros P, Stifano G, Borges CL, de Carvalho CR, Kairalla R, Parra ER, Spira A, Simms R, Capellozzi VL, Lafyatis R. Association of Interferon- and transforming growth factor beta-regulated genes and macrophage activation with systemic sclerosis-related progressive lung fibrosis. Arthritis Rheumatol. 2014;66(3):714-25. doi: 10.1002/art.38288. PubMed PMID: 24574232; PubMed Central PMCID: PMC4439004.
  • Mathes AL, Christmann RB, Stifano G, Affandi AJ, Radstake TR, Farina GA, Padilla C, McLaughlin S, Lafyatis R. Global chemokine expression in systemic sclerosis (SSc): CCL19 expression correlates with vascular inflammation in SSc skin. Ann Rheum Dis. 2014;73(10):1864-72. doi: 10.1136/annrheumdis-2012-202814. PubMed PMID: 23873879; PubMed Central PMCID: PMC4076390.