Cambridge Stem Cell Institute and Department of Haematology
I am studying the role of Stat5b in the pathogenesis of myeloproliferative neoplasms (MPN) such as Polycythemia Vera. The three most common driver mutations of MPN are JAK2-V617F, CALR-mutations and mutations of the thrombopoietin receptor MPL. It has recently been shown, that JAK2 mutant haematopoiesis causes metabolic alterations including hypoglycaemia and adipose tissue atrophy.
I am interesting in studying if JAK-STAT signalling might be involved in the metabolic switch from glycolysis of haematopoietic stem cells to oxidative phosphorylation in further differentiated progenitor cells.
I performed some Seahorse-experiments showing some interesting acute changes upon JAK-STAT activation that occur to quick to be explained by transcriptional changes. I would like to further investigate these studies by studying the metabolome of hematopoietic cells before and after JAK-STAT activation.
I am a trained Hhematologist and did my PhD at the University of Zurich on endothelial hemoglobin toxicity and heme-catalized lipid peroxidation. I am funded by a Swiss National Science Foundation Postdoc.Mobility Grant and a Postdoc in Tony Greens lab. On this specific project, I am currently not collaborating with someone else.
I am contacting you because I would like to track the changes in Metabolites such as aKG, Citrate, G6P, Pyruvate and others to further elucidate the molecular mechanisms of the aforementioned metabolic switch induced by JAK-STAT signalling.
Deuel JW, Vallelian F, Schaer CA, Puglia M, Buehler PW, Schaer DJ. Different target specificities of haptoglobin and hemopexin define a sequential protection system against vascular hemoglobin toxicity.
Deuel JW, Schaer CA, Boretti FS, Opitz L, Garcia-Rubio I, Baek JH, Spahn DR, Buehler PW, Schaer DJ. Hemoglobinuria-related acute kidney injury is driven by intrarenal oxidative reactions triggering a heme toxicity response.
Schaer CA*, Deuel JW*, Bittermann AG, Rubio IG, Schoedon G, Spahn DR, Wepf RA, Vallelian F and Schaer DJ. Mechanisms of haptoglobin protection against hemoglobin peroxidation triggered endothelial damage.
Lipiski M*, Deuel JW*, Baek JW, Engelsberger WR, Buehler PW, Schaer DJ. Human Hp1-1 and Hp2-2 phenotype-specific haptoglobin therapeutics are both effective in vitro and in guinea pigs to attenuate hemoglobin toxicity.
Yalamanoglu A, Deuel JW, Hunt RC, Baek JH, Hassell K, Redinius K, Irwin DC, Schaer DJ, Buehler PW. Depletion of haptoglobin and hemopexin promote hemoglobin-mediated lipoprotein oxidation in sickle cell disease. Am J Physiol Lung Cell Mol Physiol. 2018 Nov 1;315(5):L765-L774.
Schaer CA, Deuel JW, Schildknecht D, Mahmoudi L, Garcia-Rubio I, Owczarek C, Schauer S, Kissner R, Banerjee U, Palmer AF, Spahn DR, Irwin DC, Vallelian F, Buehler PW, Schaer DJ. Haptoglobin Preserves Vascular Nitric Oxide Signaling during Hemolysis.