Publications by authors named "Nithila A Joseph"

Article Synopsis
  • Orphan nuclear receptors (NRs) like COUP-TF1 and others are linked to telomerase-negative cancers that use an alternative mechanism (ALT) to maintain their telomeres, but their exact role in activating ALT is unknown.
  • The study shows that when these orphan NRs are attached to telomeres in human fibroblasts, they trigger the formation of specific structures (APBs) and activate ALT processes, indicating that they can induce ALT from scratch.
  • Overexpression of orphan NRs enhances ALT activity, while their removal decreases it, showing their critical role in promoting ALT, potentially offering a target for new therapies using agents like arsenic trioxide to inhibit ALT in cancer cells.
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Most cases of acquired aplastic anemia (AA) arise from autoimmune destruction of hematopoietic stem and progenitor cells. Human leukocyte antigen (HLA)-haploidentical nonmyeloablative hematopoietic stem cell transplantation (HSCT) plus post-transplantation cyclophosphamide (PTCy) is increasingly applied to salvage AA using bone marrow as graft and anti-thymocyte globulin (ATG) in conditioning. Herein, we characterize a cohort of twelve AA patients clinically and molecularly, six who possessed other immunological disorders (including two also carrying germline mutations).

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Emerging models of telomere and associated proteins in Tetrahymena have broadened our understanding of telomeric processes. In this issue of Structure, Ma et al. pinpoint a region in p50 that associates with the CST complex.

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Telomere shortening is a hallmark of aging and eventually constrains the proliferative capacity of cells. The protocols discussed here are used for monitoring telomeres comprehensively in Aeolosoma viride, a model system for regeneration studies. We present methods for analyzing the activity of telomerase enzyme in regenerating tissue by telomeric repeat amplification protocol (TRAP) assay, for comparing telomere length between existing tissue and newly regenerated tissue by telomere restriction fragment (TRF) assay, as well as for visualizing telomeres by fluorescence in situ hybridization (FISH).

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Background: Epithelial-to-mesenchymal transition (EMT) has, in recent years, emerged as an important tumor cell behavior associated with high metastatic potential and drug resistance. Interestingly, protein SUMOylation and hepatocyte growth factor could respectively reduce the effect of small molecule inhibitors on tyrosine kinase activity of mutated epidermal growth factor receptor of lung adenocarcinomas (LADC). The actual mechanism is yet to be resolved.

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In this study, we examined the role of autophagy in the initiation of lipid increases in renal epithelial HK2 cells. We found that trivalent chromium [Cr(III)] induced autophagy by activating sphingomyelin phosphodiesterase 2 (SMPD2). SMPD2 increases levels of ceramide and other lipids.

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