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You searched for +publisher:"Georgia Tech" +contributor:("Yuhong Fan"). Showing records 1 – 2 of 2 total matches.

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1. Guerrant, William. Targeted histone deacetylase inhibition.

Degree: PhD, Chemistry and Biochemistry, 2012, Georgia Tech

Histone deacetylase (HDAC) inhibitors (HDACi) have demonstrated a wealth of biological effects, including anti-proliferative, anti-inflammatory, anti-parasitic, and cognition-enhancing activities. The recent FDA approvals of the inhibitors SAHA and FK-228 have validated HDACi clinical use in cutaneous T cell lymphoma, while numerous clinical trials are currently ongoing using HDACi against a variety of disease states. While the future of the HDAC field looks increasingly promising, there are lingering issues hindering broader use. Recent data point to dysregulation of specific HDAC isoforms in many disease states. However, most current HDACi are pan-inhibitors, lacking the specificity to target individual isoforms. Adding to this, there are currently 18 identified HDAC isoforms, and most lack a defined crystal structure, further complicating the task of designing isoform-specific inhibitors. Most importantly, HDACi have demonstrated a lack of efficacy against solid tumors in the clinic, a major obstacle to broader use in cancer therapy. Several of these issues could more fully be addressed through specific targeting of HDACi, and could bring HDACi into wider and more efficacious pharmaceutical use. Targeting the specific tissue or organelle where HDAC dysregulation occurs could confer greater efficacy in vivo. To this end, we have created four classes of compounds: (1) aryltriazolyl HDACi that potently inhibit HDAC activity and prostate cancer cell growth, (2) dual-targeted inhibitors of Topoisomerase II and HDAC and (3) dual-targeted inhibitors of Topoisomerase I and HDAC, both of which have potent inhibition against both target enzymes as well as cancer cell lines, and finally (4) macrocyclic HDACi that potently inhibit the growth of lung cancer cell lines and preferentially target lung tissue in vivo. Advisors/Committee Members: Yomi Oyelere (Committee Chair), Donald Doyle (Committee Member), James Powers (Committee Member), Loren Williams (Committee Member), Yuhong Fan (Committee Member).

Subjects/Keywords: HDAC inhibitors; Drug design; Targeted drug delivery; HDAC; Histone deacetylase; Bifunctional inhibitors; Cancer therapy; Drug delivery systems; Cancer Treatment; Enzymes

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APA (6th Edition):

Guerrant, W. (2012). Targeted histone deacetylase inhibition. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/44907

Chicago Manual of Style (16th Edition):

Guerrant, William. “Targeted histone deacetylase inhibition.” 2012. Doctoral Dissertation, Georgia Tech. Accessed January 23, 2021. http://hdl.handle.net/1853/44907.

MLA Handbook (7th Edition):

Guerrant, William. “Targeted histone deacetylase inhibition.” 2012. Web. 23 Jan 2021.

Vancouver:

Guerrant W. Targeted histone deacetylase inhibition. [Internet] [Doctoral dissertation]. Georgia Tech; 2012. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1853/44907.

Council of Science Editors:

Guerrant W. Targeted histone deacetylase inhibition. [Doctoral Dissertation]. Georgia Tech; 2012. Available from: http://hdl.handle.net/1853/44907

2. Park, Hyejung. Characterization of ceramide synthases (Cers) in mammalian cells.

Degree: PhD, Biology, 2009, Georgia Tech

This thesis describes the characterization of ceramide (Cer) biosynthesis by mammalian cells. The possibility that Cer undergo developmental changes was explored using mouse embryonic stem cells versus embryoid bodies by analysis of the Cer subspecies by liquid chromatography, electrospray ionization-tandem mass spectrometry (LC ESI-MS/MS) and of the transcript levels for enzymes involved in Cer biosynthesis by qRT-PCR. Cer of embroid bodies had higher proportions of very-long-chain fatty acids, which correlated with the relative expression of mRNA for the respective Cer synthases (CerS) and fatty acyl-CoA elongases, as well as changes in the fatty acyl-CoA's of the cells. Therefore, it is clear that Cer subspecies change during embryogenesis, possibly for functionally important reasons. One CerS isoform, CerS2, was studied further because it has the broadest tissue distribution and a remarkable fatty acyl-CoA specificity, utilizing longer acyl-chain CoAs (C20-C26) in vitro. The fatty acid chain selectivity was refined by analysis of the Cer from livers from CerS2 null mice, which displayed very little Cer with fatty acyl chains with 24 + 2 carbons. Another interesting structural variation was discovered in studies of cells treated with fumonisin B1 (FB1), which inhibits CerS. Under these conditions, cells in culture and animals accumulate substantial amounts of a novel sphingoid base that was identified as 1-deoxysphinganine. This compound arises from utilization of L-alanine instead of L-serine by serine palmitoyltransferase (SPT) based on the inability of LYB cells, which lack SPT, to make 1-deoxysphinganine. In the absence of FB1, 1-deoxysphinganine is primarily acylated to 1-deoxydihydroceramides. These are an underappreciated category of bioactive sphingoid bases and "ceramides" that might play important roles in cell regulation and disease. In summary, cells contain a wide variety of Cer subspecies that are determined by changes in expression of CerS, enzymes that produce co-substrates (such as fatty acyl-CoAs), and the types of amino acids utilized by SPT, the initial enzyme of de novo sphingolipid biosynthesis. One can envision how these changes might impact membranes structure as well as signaling by this family of highly bioactive compounds. Advisors/Committee Members: Alfred H. Merrill, Jr (Committee Chair), John Cairney (Committee Member), M. Cameron Sullards (Committee Member), Marion B. Sewer (Committee Member), Yuhong Fan (Committee Member).

Subjects/Keywords: Ceramide; Ceramide synthase; Sphingolipid; Ceramides; Biosynthesis; Biochemical engineering; Stem cells; Embryonic stem cells; Liquid chromatography; Chromatographic analysis

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

APA (6th Edition):

Park, H. (2009). Characterization of ceramide synthases (Cers) in mammalian cells. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/29616

Chicago Manual of Style (16th Edition):

Park, Hyejung. “Characterization of ceramide synthases (Cers) in mammalian cells.” 2009. Doctoral Dissertation, Georgia Tech. Accessed January 23, 2021. http://hdl.handle.net/1853/29616.

MLA Handbook (7th Edition):

Park, Hyejung. “Characterization of ceramide synthases (Cers) in mammalian cells.” 2009. Web. 23 Jan 2021.

Vancouver:

Park H. Characterization of ceramide synthases (Cers) in mammalian cells. [Internet] [Doctoral dissertation]. Georgia Tech; 2009. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1853/29616.

Council of Science Editors:

Park H. Characterization of ceramide synthases (Cers) in mammalian cells. [Doctoral Dissertation]. Georgia Tech; 2009. Available from: http://hdl.handle.net/1853/29616

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