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You searched for +publisher:"Harvard University" +contributor:("Yellen, Gary"). Showing records 1 – 2 of 2 total matches.

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Harvard University

1. Hung, Yin Pun. Single Cell Imaging of Metabolism with Fluorescent Biosensors.

Degree: 2012, Harvard University

Cells utilize various signal transduction networks to regulate metabolism. Nevertheless, a quantitative understanding of the relationship between growth factor signaling and metabolic state at the single cell level has been lacking. The signal transduction and metabolic states could vary widely among individual cells. However, such cell-to-cell variation might be masked by the bulk measurements obtained from conventional biochemical methods. To assess the spatiotemporal dynamics of metabolism in individual intact cells, we developed genetically encoded biosensors based on fluorescent proteins. As a key redox cofactor in metabolism, NADH has been implicated in the Warburg effect, the abnormal metabolism of glucose that is a hallmark of cancer cells. To date, however, sensitive and specific detection of NADH in the cytosol of individual live cells has been difficult. We engineered a fluorescent biosensor of NADH by combining a circularly permuted green fluorescent protein variant with a bacterial NADH-binding protein Rex. The optimized biosensor Peredox reports cytosolic (NADH:NAD+) ratios in individual live cells and can be calibrated with exogenous lactate and pyruvate. Notably pH resistant, this biosensor can be used in several cultured and primary cell types and in a high-content imaging format. We then examined the single cell dynamics of glycolysis and energy-sensing signaling pathways using Peredox and other fluorescent biosensors: AMPKAR, a sensor of the AMPK activity; and FOXO3-FP, a fluorescently-tagged protein domain from Forkhead transcription factor FOXO3 to report on the PI3K/Akt pathway activity. With perturbation to growth factor signaling, we observed a transient response in the cytosolic (NADH:NAD+) redox state. In contrast, with partial inhibition of glycolysis by iodoacetate, individual cells varied substantially in their responses, and cytosolic (NADH:NAD+) ratios oscillated between high and low states with a regular, approximately half-hour period, persisting for hours. These glycolytic NADH oscillations appeared to be cell-autonomous and coincided with the activation of the PI3K/Akt pathway but not the AMPK pathway. These results suggest a dynamic coupling between growth factor signaling and metabolic parameters. Overall, this thesis presents novel optical tools to assess metabolic dynamics – and to unravel the elaborate and complex integration of glucose metabolism and signaling pathways at the single cell level. Advisors/Committee Members: Yellen, Gary I..

Subjects/Keywords: fluorescent biosensor; glycolysis; NADH; single cell imaging; biology; cellular biology; molecular biology

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

APA (6th Edition):

Hung, Y. P. (2012). Single Cell Imaging of Metabolism with Fluorescent Biosensors. (Thesis). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:9572078

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Hung, Yin Pun. “Single Cell Imaging of Metabolism with Fluorescent Biosensors.” 2012. Thesis, Harvard University. Accessed October 23, 2017. http://nrs.harvard.edu/urn-3:HUL.InstRepos:9572078.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Hung, Yin Pun. “Single Cell Imaging of Metabolism with Fluorescent Biosensors.” 2012. Web. 23 Oct 2017.

Vancouver:

Hung YP. Single Cell Imaging of Metabolism with Fluorescent Biosensors. [Internet] [Thesis]. Harvard University; 2012. [cited 2017 Oct 23]. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:9572078.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hung YP. Single Cell Imaging of Metabolism with Fluorescent Biosensors. [Thesis]. Harvard University; 2012. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:9572078

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


Harvard University

2. Sprague, Jared Michael. TRPV1 Sensitization in Primary Sensory Neurons.

Degree: PhD, Biological Sciences in Dental Medicine, 2014, Harvard University

Pain is a major personal and community burden throughout the world with currently limited treatment options for persistent pain due to unacceptable side effects, dependence or frank inefficacy. It is necessary to understand the anatomical and molecular pathways leading to pain to better cope with the current challenge of treating it. Advisors/Committee Members: Woolf, Clifford (advisor), Ma, Qiufu (committee member), Gaudet, Rachelle (committee member), Yellen, Gary (committee member).

Subjects/Keywords: Neurosciences; Bortezomib; Optovin; Sensitization; TRPA1; TRPV1

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

APA (6th Edition):

Sprague, J. M. (2014). TRPV1 Sensitization in Primary Sensory Neurons. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:12274115

Chicago Manual of Style (16th Edition):

Sprague, Jared Michael. “TRPV1 Sensitization in Primary Sensory Neurons.” 2014. Doctoral Dissertation, Harvard University. Accessed October 23, 2017. http://nrs.harvard.edu/urn-3:HUL.InstRepos:12274115.

MLA Handbook (7th Edition):

Sprague, Jared Michael. “TRPV1 Sensitization in Primary Sensory Neurons.” 2014. Web. 23 Oct 2017.

Vancouver:

Sprague JM. TRPV1 Sensitization in Primary Sensory Neurons. [Internet] [Doctoral dissertation]. Harvard University; 2014. [cited 2017 Oct 23]. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12274115.

Council of Science Editors:

Sprague JM. TRPV1 Sensitization in Primary Sensory Neurons. [Doctoral Dissertation]. Harvard University; 2014. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12274115

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