Biology subjects

Huang, C.-Y.

Publications and source records attributed to Huang, C.-Y..

3 recordsLinked to original sources

bioRxiv2018

Crystal Structure of a Natural Light-Gated Anion Channelrhodopsin

The anion channelrhodopsin GtACR1 from the alga Guillardia theta is a potent neuron-inhibiting optogenetics tool. Presented here, its X-ray structure at 2.9 [A] reveals a tunnel traversing the protein from its extracellular surface to a large cytoplasmic cavity. The tunnel is lined primarily by small polar and aliphatic residues essential for anion conductance. A disulfide-immobilized extracellular cap facilitates channel closing and the ion path is blocked mid-membrane by its photoactive retinylidene chromophore and further by a cytoplasmic side constriction. The structure also reveals a novel photoactive site configuration that maintains the retinylidene Schiff base protonated when the channel is open. These findings suggest a new channelrhodopsin mechanism, in which the Schiff base not only controls gating, but also serves as a direct mediator for anion flux.

biochemistry↗

bioRxiv2018

Targeting BMI1 and MCL1 for Lung Adenocarcinoma Treatment

Lung cancer is the leading cause of cancer-associated death worldwide. Early metastasis and the recurrence remain major challenges for lung cancer treatment in clinic. Targeting the cancer stemness could be a potential strategy to restrain tumor progression. In the current study, we found that in lung adenocarcinoma (LAC), BMI1 and MCL1 play crucial roles in invasion, chemo-resistance, and tumor initiation. JNK signaling is a link between oncogenic pathway or environment stress to cancer stemness. The activation of JNK, either by EGFR or chemotherapy agent, stabilized BMI1 and MCL1 proteins through suppressing the expression of E3-ubiquitin ligase HUWE1. In lung cancer patient samples, high level of BMI1 is correlated with poor survival, and the expression of BMI1 is positively correlated with MCL1. A novel small-molecule BI-44 was synthesized, which effectively suppressed BMI1/MCL1 expression and inhibited tumor formation and progression in preclinical models. Targeting BMI1/MCL1 provides the basis for a new therapeutic approach in the treatment of LAC.

cancer biology↗

bioRxiv2017

Non-invasive detection of upper tract urothelial carcinomas through the analysis of driver gene mutations and aneuploidy in urine

Upper tract urothelial carcinomas (UTUC) of the renal pelvis or ureter can be difficult to detect and challenging to diagnose. Here, we report the development and application of a non-invasive test for UTUC based on molecular analyses of DNA recovered from cells shed into the urine. The test, called UroSEEK, incorporates assays for mutations in eleven genes frequently mutated in urologic malignancies and for allelic imbalances on 39 chromosome arms. At least one genetic abnormality was detected in 75% of urinary cell samples from 56 UTUC patients but in only 0.5% of 188 samples from healthy individuals. The assay was considerably more sensitive than urine cytology, the current standard-of-care. UroSEEK therefore has the potential to be used for screening or to aid in diagnosis in patients at increased risk for UTUC, such as those exposed to herbal remedies containing the carcinogen aristolochic acid.

cancer biology↗