The goal of my lab is to understand how external and internal signals are integrated by hematopoietic stem cells (HSC), translated into nuclear signals and formulate HSC decisions between self-renewal and differentiation.  Hematopoietic stem cells (HSCs) are formed and actively proliferate during development to populate the adult hematopoietic organs, such as the bone marrow in mammals. In adulthood, HSCs are quiescent, but they can be activated by stress signals and start proliferating to replenish the system with newly differentiated cells. This regenerative process has many common features with HSC formation during development. Additionally, hematopoietic diseases and especially leukemia can also be linked to development of HSCs since many developmental pathways are reactivated in cancer. For this reason, our laboratory studies hematopoiesis both during development, stress-induced regeneration and disease, focusing on the molecular mechanisms shared between these systems. Currently, we are focusing on how transposable elements signal to innate immune sensors to instruct or affect HSC decisions. To achieve our goals, we use complementary model systems, including human primary hematopoietic cells, zebrafish and mouse and we integrate wet lab and bioinformatic approaches.

Keywords:

hematopoiesis, hematopoietic stem cells, transposable elements, innate immune signaling, regeneration, chemotherapy, development, leukemia

10 selected publications

• A metabolic interplay coordinated by HLX regulates myeloid differentiation and AML through partly overlapping pathways.
  Piragyte I, Clapes T, Polyzou A, Klein Geltink RI, Lefkopoulos S, Yin N, Cauchy P, Curtis JD, Klaeylé L, Langa X, Beckmann CCA, Wlodarski MW, Müller P, Van Essen D, Rambold A, Kapp FG, Mione M, Buescher JM, Pearce EL, Polyzos A, Trompouki E. (2018).
  Nat Commun. 9(1):3090.
• 2. Protection from UV light is an evolutionarily conserved feature of the haematopoietic niche.
  Kapp FG, Perlin JR, Hagedorn EJ, Gansner JM, Schwarz DE, O'Connell LA, Johnson NS, Amemiya C, Fisher DE, Wölfle U, Trompouki E, Niemeyer CM, Driever W, Zon LI. (2018).
  Nature 558, 445-448
• 3. Genome-wide trans-ethnic meta-analysis identifies seven genetic loci influencing erythrocyte traits and a novel role for RBPMS in erythropoiesis.
  Van Rooij JA F. ….Trompouki E., …, Ganesh SK. (2017).
  American Journal of Human Genetics, 100, 51-63.
• MED12 Regulates HSC-Specific Enhancers Independently of Mediator Kinase Activity to Control Hematopoiesis.
  Aranda-Orgilles B, Saldaña-Meyer R, Wang E, Trompouki E, Fassl A, Lau S, Mullenders J, Rocha PP, Raviram R, Guillamot M, Sánchez-Díaz M, Wang K, Kayembe C, Zhang N, Amoasii L, Choudhuri A, Skok JA, Schober M, Reinberg D, Sicinski P, Schrewe H, Tsirigos A, Zon LI, Aifantis I. (2016).
  Cell Stem Cell 19, 784-799
• Dynamic Control of Enhancer Repertoires Drives Lineage and Stage-Specific Transcription during Hematopoiesis.
  Huang J, Liu X, Li D, Shao Z, Cao H, Zhang Y, Trompouki E, Bowman TV, Zon LI, Yuan GC, Orkin SH, Xu J. (2016).
  Dev Cell 36, 9-23.
• Angiopoietin-like proteins stimulate HSPC development through interaction with notch receptor signaling.
  Lin MI, Price EN, Boatman S, Hagedorn EJ, Trompouki E, Satishchandran S, Carspecken CW, Uong A, DiBiase A, Yang S, Canver MC, Dahlberg A, Lu Z, Zhang CC, Orkin SH, Bernstein ID, Aster JC, White RM, Zon LI. (2016)
  Elife. 4:e05544
• Nanog-like regulates endoderm formation through the Mxtx2-Nodal pathway.
  Xu C, Fan ZP, Müller P, Fogley R, DiBiase A, Trompouki E, Unternaehrer J, Xiong F, Torregroza I, Evans T, Megason SG, Daley GQ, Schier AF, Young RA, Zon LI. (2012).
  Dev Cell22, 625-38.
• Lineage regulators direct BMP and Wnt pathways to cell-specific programs during differentiation and regeneration.
  Trompouki E*, Bowman TV*, Lawton LN, Fan ZP, Wu DC, DiBiase A, Martin CS, Cech JN, Sessa AK, Leblanc JL, Li P, Durand EM, Mosimann C, Heffner GC, Daley GQ, Paulson RF, Young RA, Zon LI. (2011).
  Cell 28, 577-89
• Truncation of the catalytic domain of the cylindromatosis tumor suppressor impairs lung maturation.
  Trompouki E, Tsagaratou A, Kosmidis SK, Dollé P, Qian J, Kontoyiannis DL, Cardoso WV, Mosialos G. (2009)
  Neoplasia 11, 469-76.
• CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members.
  Trompouki E, Hatzivassiliou E, Tsichritzis T, Farmer H, Ashworth A, Mosialos G. (2003)
  Nature 424, 793-6.