Biology subjects

Yu, S. M.

Publications and source records attributed to Yu, S. M..

3 recordsLinked to original sources

bioRxiv2026

Molecular Imaging of Collagen Turnover in Myocardial Infarction

Cardiac fibrosis is a key contributor to cardiomyopathy after myocardial infarction (MI). Existing imaging techniques can detect established fibrotic changes; however, they lack sensitivity for ongoing collagen turnover--a dynamic process involving the denaturation of collagen triple helix. Molecular imaging of this process could enhance risk assessment and aid in the development of anti-fibrotic treatments. This study aimed to evaluate 99mTc-(HE)-(GPO), a radiotracer designed to target denatured collagen, as a biomarker of collagen turnover after MI. Methods99mTc-(HE)-(GPO) incorporates glycine-proline-hydroxyproline (GPO) repeats and can hybridize with denatured single- or double-stranded collagen. MI was induced in mice by ligation of the left anterior descending artery; sham-operated animals served as controls. At 2 weeks post-MI, animals underwent myocardial perfusion imaging or contrast-enhanced CT to detect the infarct zone, followed by SPECT/CT imaging using 99mTc-(HE)-(GPO) or a control scrambled tracer. Tracer uptake was quantified in vivo and ex vivo with gamma counting and autoradiography. Different aspects of fibrosis were examined by tissue analysis, along with autoradiography with a matrix metalloproteinase-targeted radiotracer, 99mTc-RYM1. Tracer binding was also assessed in human cardiac tissue through ex vivo autoradiography. Results99mTc-(HE)-(GPO) SPECT/CT revealed significantly higher tracer uptake in the infarct zone of MI mice compared to the remote zone and sham controls (P < 0.0001 for both). Tracer uptake was confirmed by autoradiography, which showed a strong correlation between SPECT and autoradiography (R = 0.81, P < 0.01). The scrambled tracer exhibited minimal cardiac uptake, demonstrating the specificity of 99mTc-(HE)-(GPO) signal. Denatured collagen staining and 99mTc-RYM1 autoradiography showed similar patterns as ex vivo 99mTc-(HE)-(GPO) autoradiography, while the ratio of denatured collagen to procollagen in the infarct zone significantly increased from day 3 to 2 weeks post-MI. Finally, 99mTc-(HE)-(GPO) bound to human fibrotic (but not normal) cardiac tissue. Conclusion99mTc-(HE)-(GPO) enables non-invasive detection of denatured collagen as a marker of collagen remodeling in vivo, offering a promising tool for assessing fibrotic remodeling after MI. Collagen, procollagen, and denatured collagen, along with MMP activation, exhibit distinct patterns, and their combined imaging may provide a comprehensive molecular fingerprint of cardiac fibrosis, advancing personalized management of cardiomyopathy.

bioengineering↗

bioRxiv2022

Targeting Damaged Collagen for Intra-Articular Delivery of Therapeutics using Collagen Hybridizing Peptides

The objective of this study was to investigate the potential of collagen hybridizing peptides (CHPs), which bind to denatured collagen, to extend the retention time of near-infrared fluorophores (NIRF) following intra-articular (IA) injection in rat knee joints. CHPs were synthesized with a NIRF conjugated to N-terminus. Male Sprague-Dawley rats were assigned to one of four experimental groups: healthy, CHP; osteoarthritis (OA), CHP; healthy, scrambled-sequence CHP (sCHP), which has no collagen binding affinity; or OA, sCHP. Animals in the OA groups received an IA injection of monosodium iodoacetate to induce OA. All animals then received the corresponding CHP injection. Animals were imaged repeatedly over two weeks using an in vivo fluorescence imaging system. Joint components were isolated and imaged to determine CHP binding distribution. Safranin-O and Fast Green histological staining was performed to confirm the development of OA. CHPs were found to be retained within the joint following IA injection in both healthy and OA animals for the full study period. In contrast, sCHPs were cleared within 24-48 hours. CHP signal was significantly greater (p<0.05) in OA joints when compared to healthy joints. At the two-week end point, multiple joint components retained CHPs, including cartilage, meniscus, and synovium. CHPs extended the retention time of NIRFs following IA injection in healthy and OA knee joints by binding to multiple collagenous tissues in the joint. These results support the pursuit of further research on CHP based therapeutics for IA treatment of OA.

bioengineering↗

bioRxiv2017

Reconstructing the evolution of metabolism in budding yeasts

Budding yeasts inhabit a range of environments by exploiting various metabolic traits. The genetic bases for these traits are mostly unknown, preventing their addition or removal in a chassis organism for metabolic engineering. To help understand the molecular evolution of these traits in yeasts, we created Analyzing Yeasts by Reconstructing Ancestry of Homologs (AYbRAH), an open-source database of predicted and manually curated ortholog groups for 33 diverse fungi and yeasts in Dikarya, spanning 600 million years of evolution. OrthoMCL and OrthoDB were used to cluster protein sequence into ortholog and homolog groups, respectively; MAFFT and PhyML were used to reconstruct the phylogeny of all homolog groups. Ortholog assignments for enzymes and small metabolite transporters were compared to their phylogenetic reconstruction, and curated to resolve any discrepancies. Information on homolog and ortholog groups can be viewed in the AYbRAH web portal (https://kcorreia.github.io/aybrah/) to review ortholog groups, predictions for mitochondrial localization and transmembrane domains, literature references, and phylogenetic reconstructions. Ortholog groups in AYbRAH were compared to HOGENOM, KEGG Orthology, OMA, eggNOG, and PANTHER. PANTHER and OMA had the most congruent ortholog groups with AYbRAH, while the other phylogenomic databases had greater amounts of under-clustering, over-clustering, or no ortholog annotations for proteins. Future plans are discussed for AYbRAH, and recommendations are made for other research communities seeking to create curated ortholog databases.

evolutionary biology↗