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You searched for +publisher:"Texas A&M University" +contributor:("Dees, W. Les"). Showing records 1 – 2 of 2 total matches.

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Texas A&M University

1. Scribner, Kelly C. Regulation of Mammary cell Differentiation and Metabolism by Singleminded-2s.

Degree: PhD, Toxicology, 2013, Texas A&M University

Ductal carcinoma in situ (DCIS) has been shown to be a precursor to invasive ductal cancer (IDC). Though the progression of DCIS to IDC is believed to be an important aspect of tumor aggressiveness, prognosis and molecular markers that predict progression are poorly understood. Therefore, determining the mechanisms by which some DCIS progress is critical for future breast cancer diagnostics and treatment. Singleminded-2s (SIM2s) is a member of the bHLH/PAS family of transcription factors and a key regulator of differentiation. SIM2s is highly expressed in mammary epithelial cells and lost in breast cancer. Loss of Sim2s causes aberrant mouse mammary development with features suggestive of malignant transformation, whereas over-expression of Sim2s promotes precocious alveolar differentiation, suggesting that Sim2s is required for establishing and enhancing mammary gland differentiation. We hypothesize that SIM2s expression must be lost in premalignant lesions for breast cancer to develop. We first analyzed Sim2s in the involuting mammary gland, which is a highly tumorpromoting environment. Sim2s is down-regulated during involution, and forced expression delays involution. We then analyzed SIM2s expression in human breast cancer samples and found that SIM2s is lost with progression from DCIS to IDC, and this loss correlates with metastasis. SIM2s expression in DCIS promoted a differentiated phenotype and suppressed genes associated with de-differentiation. Furthermore, loss of SIM2s expression in DCIS xenografts increased metastasis likely due to an increase in hedgehog signaling and matrix metalloproteinase expression. Interestingly, we found metabolic shifts with gain and loss of SIM2s in not only DCIS cells, but also MCF7 and SUM159 cells. SIM2s expression decreased aerobic glycolysis and promoted oxidative phosphorylation through direct upregulation of CDKN1a and senescence. Loss of SIM2s, conversely, promotes mitochondrial dysfunction and induction of the Warburg effect. This is the first time CDKN1a and cellular senescence have been indicated as causative to metabolic shifts within cancer cells. These studies show a new role for SIM2s in metabolic homeostasis, and this regulation is lost during tumorigenesis. These data indicate SIM2s is at the apex where aging, metabolism, and disease meet – regulating the delicate relationship between the three. Advisors/Committee Members: Porter, Weston W (advisor), Safe, Stephen (committee member), Dindot, Scott (committee member), Dees, W. Les (committee member), Phillips, Tim (committee member).

Subjects/Keywords: Breast Cancer; Warburg Effect; Metabolism; Singleminded-2s; Mammary gland

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APA (6th Edition):

Scribner, K. C. (2013). Regulation of Mammary cell Differentiation and Metabolism by Singleminded-2s. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/151007

Chicago Manual of Style (16th Edition):

Scribner, Kelly C. “Regulation of Mammary cell Differentiation and Metabolism by Singleminded-2s.” 2013. Doctoral Dissertation, Texas A&M University. Accessed May 06, 2021. http://hdl.handle.net/1969.1/151007.

MLA Handbook (7th Edition):

Scribner, Kelly C. “Regulation of Mammary cell Differentiation and Metabolism by Singleminded-2s.” 2013. Web. 06 May 2021.

Vancouver:

Scribner KC. Regulation of Mammary cell Differentiation and Metabolism by Singleminded-2s. [Internet] [Doctoral dissertation]. Texas A&M University; 2013. [cited 2021 May 06]. Available from: http://hdl.handle.net/1969.1/151007.

Council of Science Editors:

Scribner KC. Regulation of Mammary cell Differentiation and Metabolism by Singleminded-2s. [Doctoral Dissertation]. Texas A&M University; 2013. Available from: http://hdl.handle.net/1969.1/151007

2. Bawa, Bhupinder. Neurodegeneration in cerebellar granule cells of p/q type voltage gated calcium channel mutant leaner mice.

Degree: PhD, Veterinary Anatomy, 2009, Texas A&M University

Mutations of the α1A subunit of CaV 2.1 voltage gated calcium (VGCC) channels are responsible for several inherited disorders affecting humans, including familial hemiplegic migraine, episodic ataxia type and spinocerebellar ataxia type. The leaner mouse also carries an autosomal recessive mutation in the α1A subunit of CaV 2.1 VGCCs, which, in the homozygous condition, results in a severe cerebellar atrophy and ataxia. The leaner mutation results in reduced calcium influx through CaV 2.1 VGCCs. To better understand cerebellar neurodegeneration and cerebellar dysfunction we focused our research on elucidating the relationship between mitochondrial function/dysfunction and calcium channel mutations. The aims of this dissertation were: 1) to estimate the extent of neuronal cell death, basal intracellular calcium and mitochondrial (dys)function in cerebellar granule cells (CGC) of adult leaner mice; 2) to analyze the role of the leaner calcium channel mutation on postnatal development of CGCs; and 3) to test whether inducing increased calcium influx by exposing cultured granule cells to potassium chloride can eliminate or reduce the CGC death. By using mechanism independent Fluoro-Jade staining and apoptosis specific TUNEL staining, we demonstrated that leaner CGC death continues into adulthood and the spatial pattern of granule cell death observed during postnatal development also continues into adulthood. The present investigation showed a reduced resting intracellular calcium in CGC from leaner mice as compared to age matched wild type mice, and tottering mice. The tottering mouse is another mutant mouse that carries a mutation in the α1A subunit of CaV 2.1 VGCCs like leaner mouse. However, these mice do not show any neurodegeneration and therefore they were used as a second control. Our results also showed that even though CGC of leaner mice have dysfunctional CaV2.1 channels, there is no change in depolarization induced Ca2+ influx, which suggests a functional compensation for CaV2.1 calcium channels by other VGCCs. Our results showed reduced mitochondrial membrane potential at the time of peak CGC death in leaner mice as compared to wild type CGCs and tottering CGCs. The results of this investigation suggest mitochondrial mediated but reactive oxygen species independent cell death in CGCs of leaner mice. Advisors/Committee Members: Abbott, Louise C. (advisor), Dees, W. Les (committee member), Griffith, William (committee member), Welsh, C. Jane (committee member).

Subjects/Keywords: Neurodegeneration; cerebellum; Leaner; calcium channels

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Bawa, B. (2009). Neurodegeneration in cerebellar granule cells of p/q type voltage gated calcium channel mutant leaner mice. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/ETD-TAMU-2609

Chicago Manual of Style (16th Edition):

Bawa, Bhupinder. “Neurodegeneration in cerebellar granule cells of p/q type voltage gated calcium channel mutant leaner mice.” 2009. Doctoral Dissertation, Texas A&M University. Accessed May 06, 2021. http://hdl.handle.net/1969.1/ETD-TAMU-2609.

MLA Handbook (7th Edition):

Bawa, Bhupinder. “Neurodegeneration in cerebellar granule cells of p/q type voltage gated calcium channel mutant leaner mice.” 2009. Web. 06 May 2021.

Vancouver:

Bawa B. Neurodegeneration in cerebellar granule cells of p/q type voltage gated calcium channel mutant leaner mice. [Internet] [Doctoral dissertation]. Texas A&M University; 2009. [cited 2021 May 06]. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2609.

Council of Science Editors:

Bawa B. Neurodegeneration in cerebellar granule cells of p/q type voltage gated calcium channel mutant leaner mice. [Doctoral Dissertation]. Texas A&M University; 2009. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2609

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