Parasitologist &immunologist. Using inflammasome and immune cells receptor activations to understand host-parasite interaction in clinically important diseases
New paper today:
Clonorchis sinensis and cholangiocarcinoma: molecular mechanisms and biomarker advances
https://t.co/TPkNIEmSQM
Abstract: Clonorchis sinensis, a common food-borne liver fluke in East Asia, is a Group 1 carcinogen strongly linked to cholangiocarcinoma. In recent years, molecular biology and multi-omics studies have revealed that this parasite drives chronic inflammation of the bile duct epithelium, epigenetic abnormalities, and the formation of precancerous lesions. Concurrently, circulating miRNAs, DNA methylation patterns, differential protein expression, metabolite profiles, and parasite-specific antigens have been proposed as potential early molecular biomarkers, which offers new avenues for the non-invasive detection of precancerous conditions. However, current research mainly remains at the laboratory stage and studies have small-scale cohorts, lacking multi-center, large-sample prospective validation and standardized detection protocols, which limits their clinical applicability. Furthermore, traditional imaging and histological methods exhibit limited sensitivity for early identification. This review aims to systematically summarize the molecular carcinogenic mechanisms associated with C. sinensis infection, recent advances in molecular biomarker research, and strategies for identifying precancerous lesions. It will particularly focus on discussing the major obstacles in clinical translation and future directions, with the goal of providing insights for early screening and prevention strategies.
A new mechanism for “RNA memory”! 😱
Thrilled to share another crazy paper from the lab (can’t believe we posted 2 in 2 days!), summarizing >10 years of research:
Work on transgenerational inheritance of small RNAs in the powerful model organism C. elegans changed how we think about what’s possible in inheritance and evolution, because it allows the most heretical thing: inheritance of parental responses to the environment! However, it’s still unclear whether RNAs are inherited across generations in other animals, largely because the RNA-dependent RNA polymerases that amplify heritable small RNAs and prevent their dilution in C. elegans are not conserved in mammals.
In this new work, an amazing collaboration with the Rink and Wurtzel labs, we show that planarians establish long-lasting and heritable small RNA–based gene regulatory states despite lacking canonical RNA-dependent RNA polymerases and nuclear RNAi machinery (that are required in C. elegans).
You might say “they are both worms…” BUT planarians are evolutionarily very distant from C. elegans (flatworms vs. roundworms, diverged more than 500 million years ago), making this particularly surprising. These are totally different animals.
We find that ingestion of double-stranded RNA induces sequence-specific silencing that persists for months and survives repeated cycles of whole-body regeneration. Even more strikingly, RNAi can be transferred between animals, echoing James V. McConnell’s controversial “RNA memory” experiments from the 1970s (his lab was targeted by the Unabomber terrorist Ted Kaczynski, who sent McConnell a bomb. This and other controversies ended this line of experiments…)
Mechanistically, we find that the response transitions from a transient systemic dsRNA-triggered phase to a stable, cell-autonomous post-transcriptional “memory phase” maintained by antisense small RNAs. Using a new luminescence reporter (transgenesis is currently impossible in planarians), we show that silencing spreads along the targeted gene and identify a weird type of planarian small RNAs with untemplated polyA tails.
RNAi inheritance without canonical RdRPs establishes planarians as a powerful system for studying RNA-based regulatory inheritance beyond C. elegans and raises the possibility that RNA-mediated inheritance may be more broadly conserved in animals, potentially even in mammals.
Here’s a video of a planarian that is treated by RNAi against β-catenin and develops multiple heads instead of just one. This is one of the phenotypes that is inherited. Another phenotype is “loss of eyes” (which we show is not only inherited across multiple regeneration cycles, but can also be transmitted between animals in transplantation experiments).
Amazing work led by first authors Prakash Cherian and Idit Aviram (co-supervised by Omri and me).
Please read the preprint, the link is in the next tweet, and share!
A cancer cell videoed through a microscope. It has 3 nuclei (magenta). The powerhouse/overlords of the cell, mitochondria, are also shown (green). #CellBiology
I'm skeptical of most AI advice on social media.
Here's why:
Salt and sugar look the same to the untrained eye.
Someone can look smart on the surface. Polished threads. Confident takes. But unless they're in the trenches (e.g., coding with Claude Code, building real things, pushing their token limits) how do you know they're not just performing expertise?
The people who've spent more time optimizing their posts than actually using AI tools?
They're everywhere here.
Trust the builders.
Not the broadcasters.
Lactate, a metabolite with big capacities to regulate its own metabolism. Why has lactate this “metabolic power”?
Check the following paper titled “Lactate homeostasis is maintained through regulation of glycolysis and lipolysis.”
Well done to authors!
https://t.co/fVL7TrBxRA