Browsing by Author "Sankaranarayanan, Ishwarya"
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Item A New Perspective on the Heterogeneity of Cancer Glycolysis(2018-10-22) Neugent, Michael L.; Goodwin, Justin; Sankaranarayanan, Ishwarya; Yetkin, Celal Emre; Hsieh, Meng-Hsiung; Kim, Jung-whan; Neugent, Michael L.; Sankaranarayanan, Ishwarya; Yetkin, Celal Emre; Hsieh, Meng-Hsiung; Kim, Jung-whanTumors are dynamic metabolic systems which highly augmented metabolic fluxes and nutrient needs to support cellular proliferation and physiological function. For many years, a central hallmark of tumor metabolism has emphasized a uniformly elevated aerobic glycolysis as a critical feature of tumorigenecity. This led to extensive efforts of targeting glycolysis in human cancers. However, clinical attempts to target glycolysis and glucose metabolism have proven to be challenging. Recent advancements revealing a high degree of metabolic heterogeneity and plasticity embedded among various human cancers may paint a new picture of metabolic targeting for cancer therapies with a renewed interest in glucose metabolism. In this review, we will discuss diverse oncogenic and molecular alterations that drive distinct and heterogeneous glucose metabolism in cancers. We will also discuss a new perspective on how aberrantly altered glycolysis in response to oncogenic signaling is further influenced and remodeled by dynamic metabolic interaction with surrounding tumor-associated stromal cells.Item Targeting T Cells and a Novel Neurotrophic Factor to Treat Paclitaxel-induced Peripheral Neuropathy in Mice(August 2022) Sankaranarayanan, Ishwarya; Price, Theodore J; Rennaker II, Robert L; Dussor, Gregory; McIntyre Rodriguez, Christa; Burton, MichaelChemotherapy-induced peripheral neuropathy (CIPN) is a challenging condition to treat and arises due to the severe, dose-limiting toxicity of chemotherapeutic drugs such as paclitaxel. Thirty-70% of patients are affected by CIPN. Neurotoxicity associated with CIPN often results in damage to the peripheral nerves and dorsal root ganglia (DRG) and causes debilitating sensory deficits. Presently, there are no effective treatments to prevent or reduce CIPN. Here we sought to investigate two new approaches to treat CIPN. In the first approach we took advantage of immune cell interactions that occur in CIPN. Immune cells have been associated in the development and progression of the disease and disease resolution. We investigated the potential role of Inducible co- stimulatory molecule (ICOS) in the resolution of paclitaxel-induced peripheral neuropathy in mice. ICOS is an immune checkpoint molecule that is expressed on the surface of activated T cells and promotes proliferation and differentiation of T cells. In the second approach we investigated the potential antinociceptive effects of recombinant mouse Meteorin (rmMeteorin) using the paclitaxel-induced peripheral neuropathy model in male and female mice. Meteorin, a novel neurotrophic factor with an uncharacterized receptor, has been shown to mediate the reversal of neuropathic pain injured model. Our findings indicate that both approaches produce a robust antinociceptive effect in paclitaxel- induced peripheral neuropathy in mice. Modulating T cells into an anti-inflammatory phenotype, using ICOS, and using neurotrophic factors such as Meteorin could provide novel and effective therapeutics that are urgently needed for CIPN.