Sex, Drugs and Metabolomics: Sex- and Drug-Specific Characteristics and Longitudinal Metabol(om)ic Changes in Metabolic Disease
This PhD project is designed to assess hormonal, metabolic and metabolomic in subgroups of dyslipidemic patients in a cross-sectional and longitudinal manner. These subgroups consist of patients taking a low-dose statin therapy, patients taking a high-dose statin therapy, patients taking PCSK9 inhibitors and patients taking both statins and PCSK9 inhibitors. Moreover, each group will be stratified for sex, age and comorbidity. Likewise, longitudinal changes regarding hormone levels, metabolites, liver fat content and bile acid pool composition will be assessed and stratified according to sex, age and medication status.
To complement the clinical findings, mouse studies will be used to assess the effects of different lipid lowering agents, namely statins (in low, intermediate and high dosages), PCSK9 inhibitors, inclisiran and bempedoic acid, on metabolically highly relevant tissues like liver, muscle and adipose tissue. Several biochemical analyses like triglyceride extraction, cholesterol and glycogen assays, RT-qPCR and western blotting will be used to detect therapy-associated effects on tissues.
The aforementioned research questions will be put into an age-, sex- and drug-specific context and assessed together. Thus, the goal is to detect patients who either respond extraordinarily well or disadvantageous to certain treatments and which might normally stay “hidden behind the masses”. Furthermore, pathophysiological aspects will be covered through the implementation of basic science methodologies.
Methods and Skills:
Clinical studies; RT-qPCR; R programming; cell culture; biochemical assays
Leutner M, Butylina M, Matzhold C, Klimek P, Cuhaj C, Bellach L, Baumgartner-Parzer S, Reiter B, Preindl K, Kautzky A, Stimpfl T, Thurner S, Pietschmann P, Fürnsinn C, Kautzky-Willer A. Simvastatin therapy in higher dosages deteriorates bone quality: Consistent evidence from population-wide patient data and interventional mouse studies. Biomed Pharmacother 158: 114089, 2023
Leutner M, Matzhold C, Bellach L, Deischinger C, Harreiter J, Thurner S, Klimek P, Kautzky-Willer A. Diagnosis of osteoporosis in statin-treated patients is dose-dependent. Ann Rheum Dis 78: 1706-1711, 2019
Bellach L, Eigenschink M, Hassanein A, Savran D, Salzer U, Müllner EW, Repa A, Klebermass-Schrehof K, Wisgrill L, Giordano V, Berger A. Packed red blood cell transfusion in preterm infants. Lancet Haematol 9: e615-e626, 2022
Leutner M, Haug N, Bellach L, Dervic E, Kautzky A, Klimek P, Kautzky-Willer A. Risk of typical diabetes-associated complications in different clusters of diabetic patients: analysis of nine risk factors. J Pers Med 11: 328, 2021
and several further authorships