Hypoxia pathway proteins in health and disease
Previous and Current Research
All cells in our body depend on an appropriate oxygen pressure (pO2) to function. That’s why an inadequate oxygen supply (=hypoxia) is a prominent feature in various diseased tissues. During the past decade, research in our group is focused on unraveling the influence of hypoxia pathway proteins (HPP) in physiological and pathological conditions, including cancer, inflammation, and a variety of processes in the bone/bone marrow environment, especially hematopoietic stem cell (HSC) maintenance. In parallel, we are studying other fundamental questions related to HSC fate decisions as a consequence of external stress and in the context of the bone marrow niche.
Future Projects and Goals
- HPP and Bone Marrow. Defining the impact of HPP in blood vessel activity, and HSC/bone homeostasis.
- HPP and Metastasis. Characterizing the role of HPP in disseminated cancer cells and stromal cells on colonizing and propagating during metastatic processes.
- HPP and Wound Healing. Unraveling the influence of HPP on keratinocytes, blood vessels and leukocytes, during the different phases of wound healing.
- HPP and adrenal gland. Identifying the effect of HPP in adrenal cortex, medulla, and beyond.
Methodological and Technical Expertise
- Inflammatory mouse models
- Tumor biology
- Mouse genetics
Ramasz B, Krüger A, Reinhardt J, Sinha A, Gerlach M, Gerbaulet A, Reinhardt S, Dahl A, Chavakis T, Wielockx B*, Grinenko T*
Hematopoietic stem cell response to acute thrombocytopenia requires signaling through distinct receptor tyrosine kinases
Blood. 134(13):1046–1058 (2019) (*equally contributed as last and corresponding authors)
Grinenko T, Eugster A, Thielecke L, Ramasz B, Krüger A, Dietz S, Glauche I, Gerbaulet A, von Bonin M, Basak O, Clevers H, Chavakis T, Wielockx B
Hematopoietic stem cells can differentiate into restricted myeloid progenitors before cell division in mice
Nat Commun. 15;9(1):1898 (2018)
Singh RP*, Grinenko T*, Ramasz B, Franke K, Lesche M, Dahl A, Gassmann M, Chavakis T, Henry I, Wielockx B
Hematopoietic Stem Cells but Not Multipotent Progenitors Drive Erythropoiesis During Chronic Erythroid Stress in EPO Transgenic Mice
Stem Cell Rep. 10(6):1908–1919 (2018) (*equally contributed as first authors)
Mitroulis I, Chen L-S, Singh RP, Kourtzelis I, Economopoulou M, Kajikawa T, Troullinaki M, Ziogas A, Ruppova K, Hosur K, Maekawa T, Wang B, Subramanian P, Tonn T, Di Scala M, Hidalgo A, Wielockx B*, Hajishengallis G*, Chavakis T*
Secreted Protein Del-1 Regulates Myelopoiesis in the Hematopoietic Stem Cell Niche
J Clin Invest 127(10):3624–3639 (2017) (*equally contributed as last authors)
Franke, K, Kalucka, J, Soulafa Mamlouk, S, Singh, RP, Muschter, A, Weidemann, A, Iyengar, V, Jahn, S, Wieczorek, K, Geiger, K, Muders, M, Sykes, AM, Poitz, D, Ripich, T, Otto, T, Bergmann, S, Breier, G, Baretton, G, Fong, G, Greaves, D.R, Bornstein, S, Chavakis, T, Fandrey, J, Gassmann, M, and Wielockx, B
HIF-1α is a Protective Factor in Conditional PHD2 Deficient Mice Suffering from Severe HIF-2α-Induced Excessive Erythropoiesis.
Blood, 121(8):1436–1445 (2013)