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Accelerating the Development of Diagnostic Biomarkers and Mitigating Drugs for Radiation Injury with Quantitative Mass Spectrometry
Accelerating the Development of Diagnostic Biomarkers and Mitigating Drugs for Radiation Injury with Quantitative Mass Spectrometry
상세정보
- 자료유형
- 학위논문
- Control Number
- 0015494067
- International Standard Book Number
- 9781687966216
- Dewey Decimal Classification Number
- 574
- Main Entry-Personal Name
- Liu, Kate.
- Publication, Distribution, etc. (Imprint
- [Sl] : University of California, Los Angeles, 2019
- Publication, Distribution, etc. (Imprint
- Ann Arbor : ProQuest Dissertations & Theses, 2019
- Physical Description
- 102 p
- General Note
- Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
- General Note
- Advisor: Loo, Joseph A.
- Dissertation Note
- Thesis (Ph.D.)--University of California, Los Angeles, 2019.
- Restrictions on Access Note
- This item must not be sold to any third party vendors.
- Summary, Etc.
- 요약Nuclear and radiological terrorism is an on-going public health concern, but very few effective measures exist to assess the extent of the injury or counter the injuries from these potential attacks. In response to this need, the UCLA Center for Medical Countermeasures against Radiation (CMCR) has dedicated their research efforts on radiation biodosimetry and drug development. On the diagnostic side, existing biodosimetry is only able to provide a crude estimate of radiation exposure dose. More effective diagnostic tools are needed to confirm exposure and predict tissue-specific radiation injury progression. Towards this end, we aimed to develop protein biomarkers that can assess organ-specific radiation damage. Utilizing quantitative mass spectrometry (MS)-based proteomics, we performed discovery experiments to identify proteins that have desirable biomarker characteristics. In addition, we evaluated a set of hypothesized biomarker candidates as part of antioxidant response using a targeted MS method. On the treatment side, very few medical products are available to mitigate radiation-induced injury. In fact, only three radiomitigators, through drug repurposing, have been approved by the FDA for treatment of hematopoietic acute radiation syndrome (H-ARS). The UCLA CMCR has recently identified a novel group of small molecules from high throughput screening (HTS) for inhibitors of radiation-induced apoptosis. The lead compound dramatically decreases mortality from H-ARS in mice. To elucidate the mechanism of action for the lead compound, we utilized an emerging target identification approach based on thermal stability shift upon ligand binding (i.e. thermal proteome profiling or TPP). Data from TPP experiments proposed hypothetical targets for the lead compound, which can later be validated by protein-ligand binding studies and other means.
- Subject Added Entry-Topical Term
- Chemistry
- Subject Added Entry-Topical Term
- Biochemistry
- Added Entry-Corporate Name
- University of California, Los Angeles Chemistry 0153
- Host Item Entry
- Dissertations Abstracts International. 81-04B.
- Host Item Entry
- Dissertation Abstract International
- Electronic Location and Access
- 로그인을 한후 보실 수 있는 자료입니다.
- Control Number
- joongbu:568697
MARC
008200131s2019 c eng d■001000015494067
■00520200217182355
■020 ▼a9781687966216
■035 ▼a(MiAaPQ)AAI22624660
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aLiu, Kate.
■24510▼aAccelerating the Development of Diagnostic Biomarkers and Mitigating Drugs for Radiation Injury with Quantitative Mass Spectrometry
■260 ▼a[Sl]▼bUniversity of California, Los Angeles▼c2019
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2019
■300 ▼a102 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 81-04, Section: B.
■500 ▼aAdvisor: Loo, Joseph A.
■5021 ▼aThesis (Ph.D.)--University of California, Los Angeles, 2019.
■506 ▼aThis item must not be sold to any third party vendors.
■520 ▼aNuclear and radiological terrorism is an on-going public health concern, but very few effective measures exist to assess the extent of the injury or counter the injuries from these potential attacks. In response to this need, the UCLA Center for Medical Countermeasures against Radiation (CMCR) has dedicated their research efforts on radiation biodosimetry and drug development. On the diagnostic side, existing biodosimetry is only able to provide a crude estimate of radiation exposure dose. More effective diagnostic tools are needed to confirm exposure and predict tissue-specific radiation injury progression. Towards this end, we aimed to develop protein biomarkers that can assess organ-specific radiation damage. Utilizing quantitative mass spectrometry (MS)-based proteomics, we performed discovery experiments to identify proteins that have desirable biomarker characteristics. In addition, we evaluated a set of hypothesized biomarker candidates as part of antioxidant response using a targeted MS method. On the treatment side, very few medical products are available to mitigate radiation-induced injury. In fact, only three radiomitigators, through drug repurposing, have been approved by the FDA for treatment of hematopoietic acute radiation syndrome (H-ARS). The UCLA CMCR has recently identified a novel group of small molecules from high throughput screening (HTS) for inhibitors of radiation-induced apoptosis. The lead compound dramatically decreases mortality from H-ARS in mice. To elucidate the mechanism of action for the lead compound, we utilized an emerging target identification approach based on thermal stability shift upon ligand binding (i.e. thermal proteome profiling or TPP). Data from TPP experiments proposed hypothetical targets for the lead compound, which can later be validated by protein-ligand binding studies and other means.
■590 ▼aSchool code: 0031.
■650 4▼aChemistry
■650 4▼aBiochemistry
■690 ▼a0485
■690 ▼a0487
■71020▼aUniversity of California, Los Angeles▼bChemistry 0153.
■7730 ▼tDissertations Abstracts International▼g81-04B.
■773 ▼tDissertation Abstract International
■790 ▼a0031
■791 ▼aPh.D.
■792 ▼a2019
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T15494067▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
■980 ▼a202002▼f2020
