The research lab of Sophie Paczesny, MD, PhD, is developing non-invasive blood tests integrating both proteomic and cellular biomarkers for the diagnosis and prognosis of GVHD, GVL and antitumoral responses. The laboratory has also focused on immunotherapy to treat leukemia. In the hematopoietic cell transplantation field, T cells play a major role in the GVL effect, which can eradicate tumor cells in patients who resist chemotherapy. The laboratory has recently demonstrated that IL33/ST2 pathway triggering in IL-9-secreting T cells decreases GVHD while maintaining tumor immunity through an enhanced GVL effect.
Areas of Focus
The Paczesny Lab is focused on three primary areas of medical research.
The work on proteomics and discovery of biomarkers includes the use of an omics workflow system as a discovery engine for new biomarkers of complications of post-allogeneic bone marrow transplantation, including acute and chronic graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) as well as antitumoral signatures following antibody-based or cell-based immunotherapies.
The lab’s work in allogeneic hematopoietic cell transplantation, GVHD and GVL biology and novel treatment involves implementing non-invasive blood tests for risk stratification of complications following allogeneic hematopoietic cell transplantation and validating the biological and clinical significance of those biomarkers. This research is also focused on discovering inhibitors of drug targetable biomarkers and new cell therapies to alleviate GVHD and increase GVL.
Research in novel immunotherapies to treat acute myeloid leukemia is focused on enhancing antitumor specific anti-tumor immunity via vaccination or adoptive cell transfer (ACT) or antibody-based targeting of the tumoral microenvironment.
Hematopoietic Stem Cell Transplantation
The Paczesny Lab is supported by numerous awards from the National Health Institute (NIH) specifically National Cancer Institute (NCI), National Heart, Lung and Blood Institute (NHLBI), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Marrow Donor/Be the Match Program through the Amy Strelzer Manasevit Scholar grant, Leukemia and Lymphoma Society, and Lilly Physician Scientist program. Paczesny collaborates with many prominent scientists. The laboratory collaboration list includes investigators from Memorial Sloan Kettering Cancer Center, Fred Hutchinson Cancer Research Center, Dana Farber Cancer Institute, University of Michigan, University of Minnesota, National Cancer Institute, National Heart, Lung, and Blood Institute, Boston Children’s, Texas Children’s, Universities of Paris and Nice.
Loss of epigenetic regulator TET2 and oncogenic KIT regulate myeloid cell transformation via PI3K pathway. Palam LR, Mali RS, Ramdas B, Srivatsan SN, Visconte V, Tiu RV, Vanhaesebroeck B, Roers A, Gerbaulet A, Xu M, Janga SC, Takemoto CM, Paczesny S, Kapur R. JCI Insight. 2018 Feb 22;3(4).
Murine chronic graft-versus-host disease proteome profiling discovers CCL15 as a novel biomarker in patients. Du J, Flynn R, Paz K, Ren HG, Ogata Y, Zhang Q, Gafken PR, Storer BE, Roy NH, Burkhardt JK, Mathews W, Tolar J, Lee SJ, Blazar BR, Paczesny S. Blood 2018 Jan 18
The ST2/IL-33 Axis in Immune Cells during Inflammatory Diseases. Griesenauer B, Paczesny S. Front Immunol. 2017 Apr 24;8:475.
An activated Th17-prone T cell subset involved in chronic graft-versus-host disease sensitive to pharmacological inhibition. Forcade E, Paz K, Flynn R, Griesenauer B, Amet T, Li W, Liu L, Bakoyannis G, Jiang D, Chu HW, Lobera M, Yang J, Wilkes DS, Du J, Gartlan K, Hill GR, MacDonald KP, Espada EL, Blanco P, Serody JS, Koreth J, Cutler CS, Antin JH, Soiffer RJ, Ritz J, Paczesny S, Blazar BR. JCI Insight. 2017 Jun 15;2(12).
Editorial: Danger Signals Triggering Immune Response and Inflammation. Ramadan A, Land WG, Paczesny S. Front Immunol. 2017 Aug 11;8:979.
Specifically Differentiated T Cell Subset Promotes Tumor Immunity over Fatal Immunity. Ramadan A, Griesenauer B, Adom D, Kapur R, Hanenberg H, Liu C, Kaplan MH, and Paczesny S. The Journal of Experimental Medicine, 2017, epub https://doi.org/10.1084/jem.20170041
Proteomics analysis reveals a Th17-prone cell population in presymptomatic graft-versus-host disease. Li W, Liu L, Gomez A, Zhang J, Ramadan A, Zhang Q, Choi SW, Zhang P, Greenson JK, Liu C, Jiang D, Virts E, Kelich SL, Chu HW, Flynn R, Blazar BR, Hanenberg H, Hanash S, Paczesny S. JCI Insight 2016 May 5;1(6).
Biomarker Panel for Chronic Graft-Versus-Host Disease. Yu J, Storer BE, Kushekhar K, Abu Zaid M, Zhang Q, Gafken PR, Ogata Y, Martin PJ, Flowers ME, Hansen JA, Arora M, Cutler C, Jagasia M, Pidala J, Hamilton BK, Chen GL, Pusic I, Lee SJ, Paczesny S. Journal of Clinical Oncology 2016 Aug 1;34(22):2583-90.
High day 28 ST2 levels predict for acute graft-versus-host disease and transplant-related mortality after cord blood transplantation. Ponce DM, Hilden P, Mumaw C, Devlin SM, Lubin M, Giralt S, Goldberg JD, Hanash A, Hsu K, Jenq R, Perales MA, Sauter C, van den Brink MR, Young JW, Brentjens R, Kernan NA, Prockop S, O’Reilly RJ, Scaradavou A, Paczesny S, Barker JN. Blood. 2015 Jan 1;125(1):199-205.
Various forms of tissue damage and danger signals following hematopoietic stem-cell transplantation. Ramadan A, Paczesny S. Front Immunol. 2015 Jan 28;6:14.
ST2 blockade reduces sST2-producing T cells while maintaining protective mST2-expressing T cells during graft-versus-host disease. Zhang J, Ramadan A, Griesenauer B, Li W, Turner M, Liu C, Kapur R., Hanenberg H., Blazar BR, Tawara I, and Paczesny S. Sci Transl Med 2015, 7(308): 308ra160.
ST2 as a marker for risk of therapy-resistant graft-versus-host disease and death. Vander Lugt MT, Braun TM, Hanash S, 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, Ferrara JL, Paczesny S. New England Journal Medicine 2013 August 8; 369(6):529-39.
Additional Research Team Members
Other research team members in the Paczesny Lab include Jamila Adom, PhD (post-doctoral fellow), Jennifer Yang, PhD (post-doctoral fellow) and Alex Dile (LHSI student).