Biology subjects

Lobel, L.

Publications and source records attributed to Lobel, L..

4 recordsLinked to original sources

bioRxiv2026

Western diet suppresses canonical intestinal stem cells and reprograms c-Kit+ reserve stem cells via proinflammatory dysbiosis

While colorectal cancer (CRC) is thought to originate primarily from resident stem cells, diet heavily influences intestinal stem cell homeostasis and disease onset. In this study, we demonstrate that a Western-style diet (WSD) alters intestinal homeostasis by uncoupling canonical stemness from tumorigenesis. WSD exposure suppresses canonical Lgr5 stem cells while activating an alternative pool of facultative c-Kit secretory cells. Although these reprogrammed stem-like cells exhibit genotoxic stress, they remain proliferative under prolonged dietary exposure, suggesting increased susceptibility to tumor-initiating mutations. We identify diet-induced microbial shifts and the expansion of enterotoxigenic Bacteroides fragilis (ETBF) as the upstream driver. ETBF and its toxin fragilysin autonomously trigger multipotency in c-Kit+ cells through Wnt/{beta}-catenin and YAP signaling. Importantly, these alterations are fully reversible upon dietary intervention. Together, our results highlight a targetable dietary-microbial axis that shapes epithelial stemness and underscores the role of facultative stem cells in diet-induced CRC onset.

cell biology↗

bioRxiv2024

Crimean-Congo Hemorrhagic Fever Survivors Elicit Protective Non-Neutralizing Antibodies that Target 11 Overlapping Regions on Viral Glycoprotein GP38

Crimean-Congo hemorrhagic fever virus can cause lethal disease in humans yet there are no approved medical countermeasures. Viral glycoprotein GP38, unique to Nairoviridae, is a target of protective antibodies, but extensive mapping of the human antibody response to GP38 has not been previously performed. Here, we isolated 188 GP38-specific antibodies from human survivors of infection. Competition experiments showed that these antibodies bind across five distinct antigenic sites, encompassing eleven overlapping regions. Additionally, we reveal structures of GP38 bound with nine of these antibodies targeting different antigenic sites. Although GP38-specific antibodies were non-neutralizing, several antibodies were found to have protection equal to or better than murine antibody 13G8 in two highly stringent rodent models of infection. Together, these data expand our understanding regarding this important viral protein and inform the development of broadly effective CCHFV antibody therapeutics.

immunology↗

bioRxiv2020

Diet Post-translationally Modifies The Gut Microbial Proteome To Modulate Renal Function

We identify a novel mechanism linking diet, gut microbial metabolism, and renal function. We found that a sulfur amino acid-based dietary intervention post-translationally modifies a microbial enzyme, blunting its uremic toxin-producing activity and alleviating chronic kidney disease (CKD) in a preclinical model. We also define a heretofore unknown role for the post-translational modification S-sulfhydration within the gut microbiome. This study provides a framework for understanding how diet can tune microbiota function via protein post-translational modification without altering microbial community composition to support healthy host physiology beyond the gut and specifically how a dietary modification can inhibit tryptophanase activity to ameliorate CKD progression. One Sentence SummaryWe found that diet post-translationally modifies the gut microbiota proteome to modulate kidney function.

microbiology↗

bioRxiv2018

HERD IMMUNITY TO EBOLAVIRUSES IS NOT A REALISTIC TARGET FOR CURRENT VACCINATION STRATEGIES

The recent West African Ebola virus pandemic, which affected >28,000 individuals increased interest in anti-Ebolavirus vaccination programs. Here, we systematically analyzed the requirements for a prophylactic vaccination program based on the basic reproductive number (R0, i.e. the number of secondary cases that result from an individual infection). Published R0 values were determined by a systematic literature research and ranged from 0.37 to 20. R0s [≥]4 realistically reflected the critical early outbreak phases and superspreading events. Based on the R0, the herd immunity threshold (Ic) was calculated using the equation Ic=1-(1/R0). The critical vaccination coverage (Vc) needed to provide herd immunity was determined by including the vaccine effectiveness (E) using the equation Vc=Ic/E. At an R0 of 4, the Ic is 75% and at an E of 90%, more than 80% of a population need to be vaccinated to establish herd immunity. Such vaccination rates are currently unrealistic because of resistance against vaccinations, financial/ logistical challenges, and a lack of vaccines that provide long-term protection against all human-pathogenic Ebolaviruses. Hence, outbreak management will for the foreseeable future depend on surveillance and case isolation. Clinical vaccine candidates are only available for Ebola viruses. Their use will need to be focused on health care workers, potentially in combination with ring vaccination approaches.

epidemiology↗