Sophie Paczesny, M.D., Ph.D.
Summary of the focus of the research of Dr. Paczesny
Our laboratory focuses on Hematopoietic stem cell transplantation, T cell biology, Graft-versus-Host-Disease, cytokines and cellular pathway networks, human immunology, translational medicine.
Description and summary of our laboratory's research focus
Allogeneic hematopoietic stem cell transplantation (HSCT) is a major therapy for malignant diseases of the blood and bone marrow and the most potent form of immune therapy against these diseases through its graft-versus-leukemia/tumor (GVL/GVT) effect. However, the efficacy of allogeneic HSCT has been impeded by frequent and severe graft-versus-host-disease (GVHD) that is tightly linked to the GVL/GVT effect. Both acute and chronic forms of GVHD exist. The immunobiology of GVHD and GVL responses are complex and cytokines and cellular effectors are critical. My laboratory focused on understanding the role of cytokines and cellular effectors in the biology of GVHD/GVL by discovering and investigating biomarkers in the blood and tissues of patients following allogeneic HSCT. Currently no laboratory tests exist to predict the risk of developing GVHD, responsiveness to treatment, or patient survival. The goal of our laboratory is to develop such tests integrating both proteomic and cellular biomarkers for the diagnosis and prognosis of GVHD. For proteomics, we will utilize a three-step approach: (i) discovery of proteins in an unbiased manner with a quantitative mass-spectrometry based technology, (ii) selection of the most promising candidate proteins, and (iii) validation of these candidates in a large number of allogeneic HSCT recipients using high-throughput techniques such as ELISA assays. For the study of blood cellular biomarkers, we will analyze subsets of blood cellular components that are potential GVHD biomarkers. For example, we will analyze CCR5+ regulatory T cells that migrate into chronically inflamed intestines as are found in gastrointestinal (GI) GVHD or CAMP activated plasmacytoid dendritic cells in skin GVHD. Similarly, we will analyze other subsets of cellular effectors of GVHD such as effector memory T lymphocytes expressing CD146, which may be more discernible in the circulating cells of patients with GI GVHD than in skin GVHD. We are interested in both acute and chronic GVHD, which has overlapping features of immunodeficiency and symptoms of naturally occurring autoimmune disorders. Indeed, a prominent clinical feature of chronic GVHD is a debilitating fibrosing skin disease whose gross and histologic features resemble scleroderma (SSc) and, less commonly, morphea. Because of these potential biological similarities between chronic GVHD and autoimmune diseases, our work is also relevant for those.
- Nelson RP Jr, Khawaja MR, Perkins SM, Elmore L, Mumaw CL, Orschell C, Paczesny S. Prognostic Biomarkers for Acute Graft-Versus-Host Disease Risk after Cyclophosphamide-Fludarabine Nonmyeloablative Allotransplantation. Biol Blood Marrow Transplant. 2014 Nov;20(11):1861-4. PMCID: PMC4194218.
- Kitko CL, Levine JE, Storer BE, Chai X, Fox DA, Braun TM, Couriel DR, Martin PJ, Flowers ME, Hansen JA, Chang L., Conlon M, Fiema BJ., Morgan R, Pongtornpipat P., Lamiman K., Ferrara JLM, Lee SJ., Paczesny S. Plasma CXCL9 elevations correlate with chronic GVHD diagnosis. Blood. 2014 Jan 30;123(5):786-93. PMCID: PMC 3907763
- Choi SW, Braun T, Chang L, Ferrara JL, Pawarode A, Magenau JM, Hou G, Beumer JH, Levine JE, Goldstein S, Couriel DR, Stockerl-Goldstein K, Krijanovski OI, Kitko C, Yanik GA, Lehmann MH, Tawara I, Sun Y, Paczesny S, Mapara MY, Dinarello CA, Dipersio JF, Reddy P. Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial. Lancet Oncol. 2013 Nov 29.
- Vander Lugt MT, Braun T, Hanash S, Ferrara JLM, Ritz J., Ho VT., Antin JH., Zhang Q, Wong CH., Wang H., Chin A, Gomez A, Harris AC, Levine JE, Choi SW, Couriel D, Reddy P and Paczesny S. ST2 as a marker for risk of therapy-resistant graft-versus-host disease and death. New England Journal Medicine 2013 August 8; 369(6):529-39.
- Levine JE, Logan BR, Wu J, Alousi AM, Bolaños-Meade J, Ferrara JL, Ho VT, Weisdorf DJ, Paczesny S. Acute graft-versus-host disease biomarkers measured during therapy can predict treatment outcomes: a Blood and Marrow Transplant Clinical Trials Network study. Blood. 2012 Apr 19;119(16):3854-60 PMCID: PMC3335389
- Ferrara JL, Harris AC, Greenson JK, Braun TM, Holler E, Teshima T, Levine JE, Choi SW, Huber E, Landfried K, Akashi K, Vander Lugt MT, Reddy P, Chin A, Zhang Q, Hanash S, Paczesny S. Regenerating islet-derived 3-alpha is a biomarker of gastrointestinal graft-versus-host disease. Blood 2011, 118:6702-8. PMCID:PMC3242723
- Magenau JM, Qin X, Tawara I, Rogers CE, Kitko C, Schlough M, Bickley D, Braun TM, Jang PS, Lowler KP, Jones DM, Choi SW, Reddy P, Mineishi S, Levine JE, Ferrara JL, Paczesny S. Frequency of CD4(+)CD25(hi)FOXP3(+) regulatory T cells has diagnostic and prognostic value as a biomarker for acute graft-versus-host-disease. Biol Blood Marrow Transplant 2010, 16:907-914. PMCID: PMC2916071
- Paczesny S, Braun TM, Levine JE, Hogan J, Crawford J, Coffing B, Olsen, S, Choi SW, Wang H, Faca V, Pitteri S, Zhang Q, Chin A, Kitko C, Mineishi S, Yanik G, Peres E, Hanauer D, Wang Y, Reddy P, Hanash S, and Ferrara JLM. Elafin is a biomarker of graft versus host disease of the skin. Sci Transl Med 2010, 2(13): 13ra2.* PMCID: PMC2895410
- Paczesny S, Krijanovski OI, Braun TM, Choi SW, Clouthier SG, Kuick R, Misek DE, Cooke KR, Kitko CL, Weyand A, Bickley D, Jones D, Whitfield J, Reddy P, Levine JE, Hanash SM, Ferrara JL. A biomarker panel for acute graft-versus-host disease. Blood 2009, 113(2):273-8. PMCID: PMC2615645
- Paczesny S, Banchereau J, Wittkowski KM, Saracino G, Fay J, Palucka AK. Expansion of melanoma-specific cytolytic CD8+ T cell precursors in patients with metastatic melanoma vaccinated with CD34+ progenitor-derived dendritic cells. J Exp Med. 2004 Jun 7;199(11):1503-11.
- B.S., 1989, Academy of Nancy-Metz, Nancy-Metz, France
- M.D., 1995, University of Strasbourg, France
- M.S., 1999, University of Paris VII, France
- Ph.D., 2004, University of Paris VII, France