Biology subjects

Kam, J. H.

Publications and source records attributed to Kam, J. H..

3 recordsLinked to original sources

bioRxiv2023

Multi-region spatial transcriptome analysis reveals cellular networks and pathways associated with hepatocellular carcinoma recurrence

Hepatocellular carcinomas (HCC) are driven by various etiologies and molecular diversity at presentation. Patient prognosis post-surgery is generally dismal, and the majority respond poorly to adjuvant targeted and/or immuno-therapies. Tumours are an ecosystem comprised of organization and interaction between different cell types that may contribute to clinically significant outcomes, such as disease recurrence. To better understand this phenomenon, we leveraged on a local cohort of patients with or without recurrence to generate spatial transcriptome profiles from multiple sectors from each tumour. We identified widespread gene expression intra- and inter tumour heterogeneity observed across the tumour sectors. Our analysis also revealed the cell type enrichment and localization, and ligand-receptor interactions identify a specific subset of endothelial cell enriched in primary tumours of patients with recurrence. Altogether, this study describes the spatial gene expression landscape in HCC patients associated with disease recurrence.

cancer biology↗

bioRxiv2022

Mitochondrial decline in the ageing old world primate retina: little evidence for difference between the centre and periphery

Mitochondrial decline is a key feature of ageing. The retina has more mitochondria than any other tissue and ages rapidly. To understand human retinal ageing it is critical to examine old world primates that have similar visual systems to humans, and do so across central and peripheral regions, as there is evidence for early central decline. Hence, we examine mitochondrial metrics in young and ageing Macaca fascicularis retinae. In spite of reduced ATP with age, primate mitochondrial complex activity did not decline. But mitochondrial membrane potentials were reduced significantly, and concomitantly, mitochondrial membrane permeability increased. The mitochondrial marker Tom20 declined significantly, consistent with reduced mitochondria number, while VDAC, a voltage dependent anion channel and diffusion pore associated with apoptosis increased significantly. In spite of these clear age-related changes, there was almost no evidence for regional differences between the centre and the periphery. Primate cones do not die with age, but many showed marked structural decline with vacuous spaces in proximal inner segments normally occupied by endoplasmic reticulum (ER), that regulate mitochondrial autophagy. In many peripheral cones, ER was displaced by the nucleus that transposed across the outer limiting membrane and could become embedded in mitochondrial populations. These data are consistent with significant changes in retinal mitochondria in old world primate ageing but provide little if any evidence that aged central mitochondria suffer more than those in the periphery.

neuroscience↗

bioRxiv2021

The morning burst: Shifting daily patterns of ATP production in Drosophila and temporal windows for their improvement in ageing

Mitochondria produce energy for cell function via adenosine triphosphate (ATP) and are regulated by a molecular 24h clock. Here we use Drosophila melanogaster to reveal shifts in whole animal ATP production over 24h, showing a marked peak in the morning that declines around midday and remains low from then through to the following morning. Mitochondrial membrane potential and ATP production has been shown previously to improve after long wavelength exposure, but apparently not at all times. Hence, to explore this further we exposed flies to 670nm at different times. Exposures between 08.00 and 11.00 resulted in a significant increase in ATP, while exposures at other times had no effect. Within the morning window, not all times were equally effective, however, 670nm exposure mid-morning when ATP production was maximal did not increase ATP, possibly because mitochondria lacked spare capacity at this time. Hence, in the morning there is a complex dynamic relationship between long wavelength light and mitochondria. Mitochondrial function and the influence of long wavelengths are conserved across species from fly to human, and determining the time points for light administration to improve function in ageing and disease is of key importance. Our data progress this search and reveal the outline of these times.

physiology↗