Cholinesterase Inhibitory Arisugacins L-Q from a sp. Isolate Obtained through a Citizen Science Initiative and Their Activities in a Phenotype-Based Zebrafish Assay.

Phenotype-based screening of a fungal extract library yielded an active sample from a sp. isolate that impaired zebrafish motility. Bioassay-guided purification led to the identification of 14 meroterpenoids including six new metabolites, arisugacins L-Q (, , , and -), seven known arisugacins (-, , , , and ), and one known terreulactone ().

Functional characterization of variants identified in familial adenomatous polyposis adenomas.

Germline mutations in the tumor suppressor () define Familial Adenomatous Polyposis (FAP), the genetic predisposition to developing adenomatous polyps. Recent sequencing of FAP adenomas have challenged established dogma that mutations alone represent the adenoma mutational landscape because recurrent somatic mutations in non-WNT pathway genes were also discovered. In particular, one of these novel genes, , presented E20K and E70K mutations that are predicted to be deleterious .

A metabolic switch controls intestinal differentiation downstream of polyposis coli (APC).

Elucidating signaling pathways that regulate cellular metabolism is essential for a better understanding of normal development and tumorigenesis. Recent studies have shown that , a crucial player in pyruvate metabolism, is downregulated in colon adenocarcinomas. Utilizing zebrafish to examine the genetic relationship between and a key tumor suppressor in colorectal cancer, we found that controls the levels of and that knock down of recapitulates phenotypes of impaired function including failed intestinal differentiation.

Juxtaposition of chemical and mutation-induced developmental defects in zebrafish reveal a copper-chelating activity for kalihinol F.

A major hurdle in using complex systems for drug screening is the difficulty of defining the mechanistic targets of small molecules. The zebrafish provides an excellent model system for juxtaposing developmental phenotypes with mechanism discovery using organism genetics. We carried out a phenotype-based screen of uncharacterized small molecules in zebrafish that produced a variety of chemically induced phenotypes with potential genetic parallels.