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Cellular Bioenergetics Regulates Cell Proliferation During Mammalian Regeneration, Sandeep Saxena
Cellular Bioenergetics Regulates Cell Proliferation During Mammalian Regeneration, Sandeep Saxena
Theses and Dissertations--Biology
Mammalian system consists of stress-sensing molecules that regulates their cellular response against damage, injury and oncogenic stress. During vertebrate regeneration, cells responding to injury re-enter the cell cycle and proliferate to form new tissue. Cell cycle re-entry or arrest is at least partly regulated by cellular senescence which negatively impacts the proliferative pool of cells during regeneration. What remains unclear is whether cells in regenerating systems possess an increased propensity to proliferate and are refractory to signals that induce senescence. My thesis work has focused on how fibroblasts from the ear pinna differentially regulate healing in highly regenerative mammals (e.g., …
Overcoming Treatment Resistance In Heterogeneous Tumors, Nikhil Hebbar
Overcoming Treatment Resistance In Heterogeneous Tumors, Nikhil Hebbar
Theses and Dissertations--Toxicology and Cancer Biology
Most primary tumors are heterogeneous and are often composed of therapy-sensitive and emerging therapy-resistant cancer cells. Rather unexpectedly, treatment of therapy-sensitive tumor cells in heterogeneous tumor microenvironments resulted in apoptosis of the therapy-resistant cancer cells. We identified a novel Par-4 amino-terminal fragment (PAF, which includes amino acids 1-131 of Par-4) that is produced and released by therapy-sensitive cancer cells following therapy-induced caspase-dependent cleavage of the tumor suppressor Par-4. PAF caused paracrine apoptosis in therapy-resistant cancer cells. Unlike Par-4-inducible apoptosis, which is dependent on the cell surface GRP78 receptor, PAF produced cancer-selective apoptosis independent of cell surface GRP78 function. Par-4 contains …
Cross-Talk Between The Tumor Suppressors Par-4 And P53, Tripti Shrestha Bhattarai
Cross-Talk Between The Tumor Suppressors Par-4 And P53, Tripti Shrestha Bhattarai
Theses and Dissertations--Toxicology and Cancer Biology
This work describes the fascinating interplay between two tumor suppressors Prostate apoptosis response-4 (Par-4) and p53. The guardian of the genome, p53, is frequently mutated in human cancers, and may contribute to therapeutic resistance. However, p53 is intact and functional in normal tissues, and we observed that specific activation of p53 in normal fibroblasts could induce apoptosis selectively in p53-deficient cancer cells. This paracrine apoptotic effect was executed by Par-4 secreted in response to p53 activation. Accordingly, activation of p53 in wild-type mice, but not in p53-/- or Par-4-/- mice, caused systemic elevation of Par-4 that induced apoptosis …
Calpain 5: A Non-Classical Calpain Highly Expressed In The Cns And Localized To Mitochondria And Nuclear Pml Bodies, Ranjana Singh
Calpain 5: A Non-Classical Calpain Highly Expressed In The Cns And Localized To Mitochondria And Nuclear Pml Bodies, Ranjana Singh
Theses and Dissertations--Neuroscience
Calpain 5 (CAPN5) is a non-classical member of the calpain family. It lacks the EF-hand motif characteristic of the classical calpains, calpain 1 and 2, but retains catalytic and Ca2+ binding non EF domains. Tra-3, an ortholog of CAPN5, is involved in necrotic cell death in C.elegans; although specific role of CAPN5 has not been investigated in the mammalian CNS. I compared relative mRNA levels of calpains in rat CNS, which revealed that CAPN5 is the second most highly expressed calpain. We examined relative levels of CAPN5 from late embryonic day 18 to postnatal day 90 and …