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Tumorzentrum Freiburg - CCCF

Petya Apostolova, MD

Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Freiburg

Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center - University of Freiburg

Projects/Topics:

  • Tumor and immune cell metabolism
  • Regulation of alloimmune responses after allogeneic hematopoietic stem cell transplantation
  • Immune checkpoint inhibitor therapy and novel therapies for immune-related adverse events

Metabolism is one of the key components of cell biology. Different metabolic processes determine proliferation, differentiation and phenotype of every cell. My work focusses on understanding the evolution of cancer cell metabolism in different stages of disease and how malignant cells and immune cells interact on the metabolic level. Additional research interests include the regulation of the alloimmune response after allogeneic hematopoietic cell transplantation as well as improving the understanding about immune-related adverse events during checkpoint inhibitor therapy.

 

Publications

  1. Apostolova P, Unger S, von Bubnoff D, Meiss F, Becher B, Zeiser R. Extracorporeal photopheresis for colitis induced by checkpoint-inhibitor therapy. New Engl J Med. 2020 Jan 16;382(3):294-296. doi: 10.1056/NEJMc1912274. [PMID 31940706]
  2. Tsukamoto H*, Chernogorova P (Apostolova P)*, Ayata K, Gerlach UV, Rughani A, Ritchey JW, Ganesan J, Follo M, Zeiser R*, Thompson LF*, Idzko M*. Deficiency of CD73/ecto-5'-nucleotidase in mice enhances acute graft-versus-host disease. Blood 2012 May 10;119(19):4554-64. [PMID 22262774], * co-first authors
  3. Apostolova P, Zeiser R. The Role of Purine Metabolites as DAMPs in Acute Graft-versus-Host Disease. Front Immunol. 2016 Oct 21;7:439. Review. [PMID 27818661]
  4. Apostolova P, Zeiser R. The role of danger signals and ectonucleotidases in acute graft-versus-host disease. Hum Immunol. 2016 Nov;77(11):1037-1047. Review. [PMID 26902992]
  5. Chernogorova P (Apostolova P), Zeiser R. Ectonucleotidases in solid organ and allogeneic hematopoietic cell transplantation. J Biomed Biotechnol 2012;2012:208204. Review. [PMID: 23125523]
  6. Koehn BH, Apostolova P, Haverkamp JM, Miller JS, McCullar V, Tolar J, Munn DH, Murphy WJ, Brickey WJ, Serody JS, Gabrilovich DI, Bronte V, Murray PJ, Ting JP, Zeiser R, Blazar BR. GVHD- associated, inflammasome-mediated loss of function in adoptively transferred myeloid-derived suppressor cells. Blood. 2015 Sep 24;126(13):1621-8. [PMID: 26265697]
  7. Mathew NR, Vinnakota JM, Apostolova P, Erny D, Hamarsheh S, Andrieux G, Kim JS, Hanke K, Goldmann T, Chappell-Maor L, El-Khawanky N, Ihorst G, Schmidt D, Duyster J, Finke J, Blank T, Boerries M, Blazar BR, Jung S, Prinz M, Zeiser R. Graft-versus-host disease of the CNS is mediated by TNF upregulation in microglia. J Clin Invest. J Clin Invest. 2020 Mar 2;130(3):1315-1329. doi: 10.1172/JCI130272. [PMID: 31846439]
  8. Mathew NR, Baumgartner F, Braun L, O'Sullivan D, Thomas S, Waterhouse M, Müller TA, Hanke K, Taromi S, Apostolova P, Illert AL, Melchinger W, Duquesne S, Schmitt-Graeff A, Osswald L, Yan KL, Weber A, Tugues S, Spath S, Pfeifer D, Follo M, Claus R, Lübbert M, Rummelt C, Bertz H, Wäsch R, Haag J, Schmidts A, Schultheiss M, Bettinger D, Thimme R, Ullrich E, Tanriver Y, Vuong GL, Arnold R, Hemmati P, Wolf D, Ditschkowski M, Jilg C, Wilhelm K, Leiber C, Gerull S, Halter J, Lengerke C, Pabst T, Schroeder T, Kobbe G, Rösler W, Doostkam S, Meckel S, Stabla K, Metzelder SK, Halbach S, Brummer T, Hu Z, Dengjel J, Hackanson B, Schmid C, Holtick U, Scheid C, Spyridonidis A, Stölzel F, Ordemann R, Müller LP, Sicre-de-Fontbrune F, Ihorst G, Kuball J, Ehlert JE, Feger D, Wagner EM, Cahn JY, Schnell J, Kuchenbauer F, Bunjes D, Chakraverty R, Richardson S, Gill S, Kröger N, Ayuk F, Vago L, Ciceri F, Müller AM, Kondo T, Teshima T, Klaeger S, Kuster B, Kim DDH, Weisdorf D, van der Velden W, Dörfel D, Bethge W, Hilgendorf I, Hochhaus A, Andrieux G, Börries M, Busch H, Magenau J, Reddy P, Labopin M, Antin JH, Henden AS, Hill GR, Kennedy GA, Bar M, Sarma A, McLornan D, Mufti G, Oran B, Rezvani K, Shah O, Negrin RS, Nagler A, Prinz M, Burchert A, Neubauer A, Beelen D, Mackensen A, von Bubnoff N, Herr W, Becher B, Socié G, Caligiuri MA, Ruggiero E, Bonini C, Häcker G, Duyster J, Finke J, Pearce E, Blazar BR, Zeiser R. Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells. Nat Med. 2018 Mar;24(3):282-291. [PMID: 29431743]
  9. Prestipino A, Emhardt AJ, Aumann K, O'Sullivan D, Gorantla SP, Duquesne S, Melchinger W, Braun L, Vuckovic S, Boerries M, Busch H, Halbach S, Pennisi S, Poggio T, Apostolova P, Veratti P, Hettich M, Niedermann G, Bartholomä M, Shoumariyeh K, Jutzi JS, Wehrle J, Dierks C, Becker H, Schmitt-Graeff A, Follo M, Pfeifer D, Rohr J, Fuchs S, Ehl S, Hartl FA, Minguet S, Miething C, Heidel FH, Kröger N, Triviai I, Brummer T, Finke J, Illert AL, Ruggiero E, Bonini C, Duyster J, Pahl HL, Lane SW, Hill GR, Blazar BR, von Bubnoff N, Pearce EL, Zeiser R. Oncogenic JAK2V617F causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms. Sci Transl Med. 2018 Feb 21;10(429). [PMID: 29467301]
  10. Tugues S, Amorim A, Spath S, Martin-Blondel G, Schreiner B, De Feo D, Lutz M, Guscetti F, Apostolova P, Haftmann C, Hasselblatt P, Núñez NG, Hottiger MO, van den Broek M, Manz MG, Zeiser R, Becher B. Graft-versus-host disease, but not graft-versus-leukemia immunity, is mediated by GM-CSF-licensed myeloid cells. Sci Transl Med. 2018 Nov 28;10(469). pii: eaat8410. doi: 10.1126/scitranslmed.aat8410. [PMID: 30487251]
  11. Carapito R, Jung N, Kwemou M, Untrau M, Michel S, Pichot A, Giacometti G, Macquin C, Ilias W, Morlon A, Kotova I, Apostolova P, Schmitt-Graeff A, Cesbron A, Gagne K, Oudshoorn M, van der Holt B, Labalette M, Spierings E, Picard C, Loiseau P, Tamouza R, Toubert A, Parissiadis A, Dubois V, Lafarge X, Maumy-Bertrand M, Bertrand F, Vago L, Ciceri F, Paillard C, Querol S, Sierra J, Fleischhauer K, Nagler A, Labopin M, Inoko H, von dem Borne PA, Kuball J, Ota M, Katsuyama Y, Michallet M, Lioure B, Peffault de Latour R, Blaise D, Cornelissen JJ, Yakoub-Agha I, Claas F, Moreau P, Milpied N, Charron D, Mohty M, Zeiser R, Socié G, Bahram S. Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD. Blood. 2016 Oct 13;128(15):1979-1986. [PMID: 27549307]
  12. Schönle A, Hartl FA, Mentzel J, Nöltner T, Rauch KS, Prestipino A, Wohlfeil SA, Apostolova P, Hechinger AK, Melchinger W, Fehrenbach K, Guadamillas MC, Follo M, Prinz G, Ruess AK, Pfeifer D, Del Pozo MA, Schmitt-Graeff A, Duyster J, Hippen KI, Blazar BR, Schachtrup K, Minguet S, Zeiser R. Caveolin-1 regulates TCR signal strength and regulatory T cell differentiation into alloreactive T cells. Blood. 2016 Feb 2. pii: blood-2015-09-672428. [PMID: 26837700]
  13. Zeiser R, Burchert A, Lengerke C, Verbeek M, Maas-Bauer K, Metzelder SK, Spoerl S, Ditschkowski M, Ecsedi M, Sockel K, Ayuk F, Ajib S, de Fontbrune FS, Na IK, Penter L, Holtick U, Wolf D, Schuler E, Meyer E, Apostolova P, Bertz H, Marks R, Lübbert M, Wäsch R, Scheid C, Stölzel F, Ordemann R, Bug G, Kobbe G, Negrin R, Brune M, Spyridonidis A, Schmitt-Gräff A, van der Velden W, Huls G, Mielke S, Grigoleit GU, Kuball J, Flynn R, Ihorst G, Du J, Blazar BR, Arnold R, Kröger N, Passweg J, Halter J, Socié G, Beelen D, Peschel C, Neubauer A, Finke J, Duyster J, von Bubnoff N. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015 Oct;29(10):2062-8. [PMID: 26228813]
  14. Hülsdünker J, Thomas OS, Haring E, Unger S, Gonzalo Núñez N, Tugues S, Gao Z, Duquesne S, Cywes-Bentley C, Oyardi O, Kirschnek S, Schmitt-Graeff A, Pabst O, Koenecke C, Duyster J, Apostolova P, Blaser MJ, Becher B, Pier GB, Häcker G, Zeiser R. Immunization against poly-N-acetylglucosamine reduces neutrophil activation and GVHD while sparing microbial diversity. Proc Natl Acad Sci U S A. 2019 Oct 8;116(41):20700-20706. doi: 10.1073/pnas.1908549116. Epub 2019 Sep 16. [PMID: 31527267]
  15. Holderried TAW, Fraccaroli A, Schumacher M, Heine A, Brossart P, Stelljes M, Klobuch S, Kröger N, Apostolova P, Finke J, Zeiser R, Heinicke T, Bornhäuser M, von Bergwelt-Baildon M, Tischer J, Wolf D. The role of checkpoint blockade after allogeneic stem cell transplantation in diseases other than Hodgkin's Lymphoma. Bone Marrow Transplant. 2019 Oct;54(10):1662-1667. doi: 10.1038/s41409-019-0498-0. Epub 2019 Mar 4. [PMID: 30833743]
  16. Klämbt V, Wohlfeil SA, Schwab L, Hülsdünker J, Ayata K, Apostolova P, Schmitt-Graeff A, Dierbach H, Prinz G, Follo M, Prinz M, Idzko M, Zeiser R. A Novel Function for P2Y2 in Myeloid Recipient-Derived Cells during Graft-versus-Host Disease. J Immunol. 2015 Dec 15;195(12):5795-804. doi: 10.4049/jimmunol.1501357. Epub 2015 Nov 4. [PMID: 26538394]
  17. Thompson LF, Tsukamoto H, Chernogorova P (Apostolova P), Zeiser R. A delicate balance: CD73-generated adenosine limits the severity of graft vs. host disease but also constrains the allogeneic graft vs. tumor effect. Oncoimmunology. 2013 Jan 1;2(1):e22107. [PMID: 23482243]
  18. Wirsching HG, Kretz O, Morosan-Puopolo G, Chernogorova P (Apostolova P), Theiss C, Brand-Saberi B. Thymosin β4 induces folding of the developing optic tectum in the chicken (Gallus domesticus). J Comp Neurol. 2012 Jun 1;520(8):1650-62. doi: 10.1002/cne.23004. [PMID: 22120963]

 

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