The protein homeostasis (proteostasis) network, a critical cytoprotective system that restores homeostasis in response to molecular stress, comprises distinct pathways, including the heat-shock response, unfolded protein response, oxidative stress response, and autophagy. These distinct pathways are all co-opted by tumor cells to cope with cancer-associated stress, and their activation in...
Plasminogen activator inhibitor-1 (PAI-1) is an essential mediator of senescence and a potential therapeutic target for preventing aging-related pathologies. Cellular Senescence is associated with organismal aging and related pathologies. In our study, we investigate the efficacies of PAI-1 inhibitors in both in vitro and in vivo models of homocysteine...
Uterine leiomyomas (fibroids) are a major source of gynaecologic morbidity in reproductive age women and are characterised by the excessive deposition of a disorganised extracellular matrix, resulting in rigid benign tumours. Clinically, leiomyoma patients usually present with pelvic pain, urinary incontinence, as well as heavy cyclic and non-cyclic bleeding. Curative...
Over the past fifty years, techniques for synthesizing and manipulating matter on the 1-100 nanometer scale have led to the development of nanoparticle-based approaches to both disease diagnosis and treatment. The modification of nanoparticles with biological macromolecules such as proteins and nucleic acids has led to the development of highly...
Current biomaterials-based methods for in vitro ovarian follicle culture enable individual follicles or follicle classes to survive and carry out basic functions of the ovary, including hormone and release of mature oocytes upon gonadotropin stimulation. However, these current strategies do not support the survival and maturation of isolated primordial and...
Proper spatiotemporal expression of genes is essential during development. One method of regulation of signaling-responsive genes is at the level of transcription. In this work, I present the adaptation of single molecule fluorescent in situ hybridization for use in Drosophila imaginal disc tissues in order to more precisely quantify transcript...
Evolutionary theory predicts that reproduction entails energetic costs that detract from somatic maintenance, accelerating biological aging. In women, such ‘costs of reproduction’ (CoR) are thought to arise predominantly during pregnancy and lactation, while in men the physiological effects of the steroid hormone testosterone (T) are believed to be a major...
The product of hexokinase (HK) enzymes, glucose-6-phosphate, can be metabolized through glycolysis or directed to alternative pathways, such as the pentose phosphate pathway (PPP) to generate anabolic intermediates. HK1 contains an N-terminal domain that permits mitochondrial binding, but its physiologic significance remains unclear. We generated mice lacking the HK1 mitochondrial-binding...
Mitochondria-derived reactive oxygen species (mROS) are required for the survival, proliferation, and metastasis of cancer cells. The mechanism by which mitochondrial metabolism regulates mROS levels to support cancer cells is not fully understood. To address this, we conducted a metabolism-focused CRISPR/Cas9 genetic screen and uncovered that loss of genes encoding...
Biological systems comprise diverse collections of cellular and non-cellular components with intricate relationships and dynamic interactions. To gain system-level understanding, we must be able to accurately model these systems, both experimentally and computationally. Agent-based models (ABMs) in particular are a uniquely intuitive, modular, and flexible framework capable of supporting multi-scale,...