Gesa Richter

• Doctor of Philosophy
• Principal Investigator at Sandoz

A fundamental step in developing a protein drug is the selection of a stable storage formulation that ensures efficacy of the drug and inhibits physiochemical degradation or aggregation. Here, we designed and evaluated a general workflow for screening of protein formulations based on small-angle X-ray scattering (SAXS). Our SAXS pipeline combines a...

Transcription factors harbor defined regulatory intrinsically disordered regions (IDRs), which raises the question of how they mediate binding to structured co-regulators and modulate their activity. Here, we present a detailed molecular regulatory mechanism of Forkhead box O4 (FOXO4) by the structured transcriptional co-regulator β-catenin. We fin...

Decreased cognitive performance is a hallmark of brain aging, but the underlying mechanisms and potential therapeutic avenues remain poorly understood. Recent studies have revealed health-protective and lifespan- extending effects of dietary spermidine, a natural autophagy-promoting polyamine. Here, we show that die- tary spermidine passes the bloo...

The transcription factor forkhead box protein P2 (FOXP2) is a highly conserved key regulator of embryonal development. The molecular mechanisms of how FOXP2 regulates embryonal development, however, remain elusive. Using RNA sequencing, we identified the Wnt signaling pathway as key target of FOXP2‐dependent transcriptional regulation. Using cell‐b...

Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplantation (allo-HCT) has a dismal prognosis. We found that T cells of patients relapsing with AML after allo-HCT exhibited reduced glycolysis and interferon-γ production. Functional studies in multiple mouse models of leukemia showed that leukemia-derived lactic acid (LA...

The causes for preterm birth (PTB) often remain elusive. We investigated whether circulating human milk oligosaccharides (HMOs) might be involved in modulating urinary and vaginal microbiome promoting or preventing PTB. We identified here HMOs and key microbial taxa associated with indicators of PTB. Based on our results, we propose two models for...

Significance We uncovered a molecular mechanism by which multiple importins regulate nuclear import, phase separation, and stress granule recruitment of an RNA-binding protein. Our work permitted the identification of two types of nuclear localization signal (NLS) in cold-inducible RNA-binding protein (CIRBP). We show that CIRBP, which lacks any cl...

Background Preterm birth is one of the leading causes of neonatal mortality. The causes for spontaneous preterm birth (PTB) are multifactorial and remain often unknown. In this study, we tested the hypothesis that human milk oligosaccharides (HMOs) in blood and urine modulate the maternal urinary and vaginal microbiome and influence the risk for PT...

The Hsp90 chaperone machinery in eukaryotes comprises a number of distinct accessory factors. Cns1 is one of the few essential co-chaperones in yeast, but its structure and function remained unknown. Here, we report the X-ray structure of the Cns1 fold and NMR studies on the partly disordered, essential segment of the protein. We demonstrate that C...

Allogeneic hematopoietic cell transplantation (allo-HCT) is the treatment strategy of choice for the majority of patients with acute myeloid leukemia (AML). However, about 40% of patients relapse, which is associated with a poor prognosis. Donor lymphocyte infusions (DLIs) induce remission only in a minority of relapsed AML patients. In order to un...

The genome of the yeast Saccharomyces cerevisiae encodes a canonical lipoamide dehydrogenase (Lpd1p) as part of the pyruvate dehydrogenase complex and a highly similar protein termed Irc15p (increased recombination centers 15). In contrast to Lpd1p, Irc15p lacks a pair of redox active cysteine residues required for the reduction of lipoamide and th...