Biology subjects

Baumann, F.

Publications and source records attributed to Baumann, F..

3 recordsLinked to original sources

bioRxiv2026

MicroRNA-17~92 drives metabolic programming of virus-specific effector CD4 and CD8 T cell responses

The miR-17[~]92 microRNA cluster drives oncogenesis by inducing proliferation and survival of cancer cells. A similar pro-proliferative role of miR-17[~]92 has also been identified in pathogen- and tumor-reactive T cells. However, the metabolic underpinnings of miR-17[~]92-drivenT cell expansion and effector differentiation remain undefined. Using a murine model of conditional miR-17[~]92 deletion or constitutive overexpression in viral antigen-specific CD4 or CD8 T cells, here we show that miR-17[~]92 drives terminal differentiation of CD4 and CD8 T cells through sustained activation of mTOR and glycolytic bioenergetics pathways. Constitutively increased expression of miR-17[~]92 led to a universal increase in the numbers of antigen-specific T follicular helper (TFH), T helper 1 (TH1) and cytotoxic T lymphocyte (CTL) effector subsets. During early stages of T cell activation, miR-17[~]92 overexpression was associated with increased glucose uptake and heightened glycolytic and oxidative metabolism to sustain increased proliferation in both CD4 and CD8 T cells. However, prolonged overexpression of miR-17[~]92 led to a loss of polyfunctionality and compromised metabolic fitness (glycolysis and mitochondrial respiration) by the peak of the effector responses. These studies establish miR-17[~]92 as a critical driver of T cell proliferation and effector differentiation through metabolic regulation of both effector CTL and CD4 T cell subsets (TFH and TH1) that are critical for combating viral infections. These studies form the basis for future manipulation of miR-17[~]92 gene/metabolic regulatory network to commandeer T cell immunity during infection, vaccination or cancer immunotherapy.

immunology↗

bioRxiv2026

Novel Protoporphyrinogen oxidase 1 mutations endow resistance to PPO-inhibiting herbicides in Bassia scoparia

PPO-inhibiting herbicides are widely used to manage weeds in different cropping systems, yet resistance evolution threatens their long-term efficacy. Here, we investigated the molecular basis of resistance to PPO-inhibiting herbicides in Bassia scoparia biotypes collected from four locations in North Dakota, USA. Greenhouse dose-response assays revealed high levels of resistance to saflufenacil and carfentrazone-ethyl, while fomesafen retained full efficacy across all biotypes. Resistant plants did not show increased copy number or elevated expression of PPO1 or PPO2. Sequencing of survivor plants revealed conserved PPO2 sequences, but consistent target-site substitutions at position F454 in PPO1, including F454I, F454L, and F454V. In vitro enzyme assays demonstrated that these substitutions impair PPO1 sensitivity to saflufenacil and carfentrazone-ethyl, but not to fomesafen. Ectopic expression of B. scoparia PPO1 F454 mutant variants in Arabidopsis thaliana conferred tolerance to saflufenacil and carfentrazone-ethyl, but not to fomesafen, supporting greenhouse and in vitro results. Molecular modeling indicated that the conformational flexibility and interaction profile of fomesafen enables it to maintain binding to mutated PPO1 variants, in contrast to the more rigid structures of saflufenacil and carfentrazone-ethyl. A yeast-based complementation system further confirmed that F454 substitutions decrease herbicide sensitivity. In addition, developmental profiling showed distinct expression patterns of PPO1 and PPO2 during early growth stages in B. scoparia and Amaranthus spp., highlighting isoform-specific roles. Together, these findings represent the first reported PPO1 target-site mutations in a broadleaf weed species as a key mechanism of resistance and highlight that fomesafen is effective to control resistant B. scoparia populations.

biochemistry↗

bioRxiv2024

Metastasis founder cells activate immunosuppression early in human melanoma metastatic colonization

The earliest steps of lethal metastasis in patients are incompletely understood. To dissect them, we prospectively searched for the earliest detectable disseminated cancer cells (DCC) in sentinel lymph node biopsies of 492 stage I-III patients. By visually-controlled, micromanipulator-assisted isolation and single cell transcriptome analysis of these extremely rare DCC, we identified MCSP+ melanoma cells as strong candidates for metastasis founder cells (MFC) in lymph nodes. Based on a median follow-up time of 6 years, their detection was the strongest predictor of systemic metastasis and death upon multivariable analysis. During transition from single cells to metastasis-initiating clusters, melanoma DCC were exposed to CD8 T cell attack, activated the extracellular vesicular exosomal pathway, and expressed the immunomodulatory proteins CD155 and CD276, but rarely PD-L1. CD155 and CD276-positive extracellular vesicles from patient-derived DCC models exhibited an immunosuppressive activity on CD8 T cells. Our data indicate that either direct targeting of MFC employing MCSP or their immune escape mechanisms might be key for cure of early-stage melanoma.

cancer biology↗