A5033615368- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Helminth infection and control
- Protein Degradation and Inhibitors
- Autophagy in Disease and Therapy
- Ubiquitin and proteasome pathways
- CAR-T cell therapy research
- Bipolar Disorder and Treatment
- Immune Cell Function and Interaction
- Biochemical and Molecular Research
- Adenosine and Purinergic Signaling
- Histone Deacetylase Inhibitors Research
- Peptidase Inhibition and Analysis
Max Planck Institute of Biophysics
2024
Goethe University Frankfurt
2024
Institute of Biochemistry
2024
Harvard University
2020-2022
Heidelberg University
2020-2022
Heidelberg University
2020
The autophagy-lysosome system directs the degradation of a wide variety cargo and is also involved in tumor progression. Here, we show that immunity-related GTPase family Q protein (IRGQ), an uncharacterized to date, acts quality control major histocompatibility complex class I (MHC I) molecules. IRGQ misfolded MHC toward lysosomal through its binding mode GABARAPL2 LC3B. In absence IRGQ, free heavy chains do not only accumulate cell but are transported surface, thereby promoting immune...
The mechanisms underlying resistance of the Chagas disease parasite, Trypanosoma cruzi, to current therapies are not well understood, including role metabolic heterogeneity. We found that limiting exogenous glutamine protects actively dividing amastigotes from ergosterol biosynthesis inhibitors (azoles), independent parasite growth rate. antiparasitic properties azoles derived inhibition lanosterol 14α-demethylase (CYP51) in endogenous sterol synthesis pathway. find carbons 13C-glutamine...
The majority of clinical degrader candidates utilize an immunomodulatory imide drug (IMiD)-based derivative, that directs their target substrate to the E3 ligase receptor Cereblon (CRBN), however, concomitant neo-substrate degradation by IMiDs often results in severe off-target effects. Further biophysical screening is needed discover CRBN binders might overcome these safety concerns, but previously reported protein constructs suffer significant limitations reduce applicability as tools for...
In addition to scavenging exogenous cholesterol, the parasitic kinetoplastid Trypanosoma cruzi can endogenously synthesize sterols. Similar fungal species, T. synthesizes ergostane type sterols and is sensitive a class of azole inhibitors ergosterol biosynthesis that target enzyme lanosterol 14α-demethylase (CYP51). related parasite Leishmania donovani, CYP51 essential, yet in major, cognate dispensable for growth; but not heat resistance. The essentiality specific role ergostane-type sterol...
The majority of clinical degraders utilize an immunomodulatory imide drug (IMiD)-based derivative that directs their target to the E3 ligase receptor cereblon (CRBN); however, identification IMiD molecular glue substrates has remained underexplored. To tackle this, we design human CRBN constructs, which retain all features for ternary complex formation, while allowing generation homogenous and cost-efficient expression in E. coli. Extensive profiling construct shows it be "best both worlds"...
Abstract The mechanisms underlying resistance of the Chagas disease parasite, Trypanosoma cruzi, to current therapies are not well understood, including potential role metabolic heterogeneity in modulating susceptibility intracellular amastigotes trypanocidal compounds. We found that limiting exogenous glutamine protects actively dividing from ergosterol biosynthesis inhibitors (azoles), independent parasite growth rate. antiparasitic properties azoles derived inhibition lanosterol...
Abstract In addition to scavenging exogenous cholesterol, the parasitic kinetoplastid Trypanosoma cruzi can endogenously synthesize sterols. Similar fungal species, T. synthesizes ergostane type sterols and is sensitive a class of azole inhibitors ergosterol biosynthesis that target enzyme lanosterol 14α-demethylase (CYP51). related parasite Leishmania donovani , CYP51 essential, yet in major cognate dispensable for growth; but not heat resistance. The essentiality specific role...