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Mass Spectrometry-Based Proteomic Investigations Into Human Disease
Mass Spectrometry-Based Proteomic Investigations Into Human Disease
Mass Spectrometry-Based Proteomic Investigations Into Human Disease

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20260202104658
ISBN  
9798280770874
DDC  
615
저자명  
Miles, Hannah Nicole.
서명/저자  
Mass Spectrometry-Based Proteomic Investigations Into Human Disease
발행사항  
[Sl] : The University of Wisconsin - Madison, 2025
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2025
형태사항  
227 p
주기사항  
Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
주기사항  
Advisor: Li, Lingjun;Ricke, William A.
학위논문주기  
Thesis (Ph.D.)--The University of Wisconsin - Madison, 2025.
초록/해제  
요약Mass spectrometry (MS) has become a powerful tool for examining human disease, offering high sensitivity and throughput across a wide range of analyte classes. Global proteomic profiling, achieved by coupling of liquid chromatography (LC) with tandem MS scans, commonly referred to as LC-MS/MS, has become a powerful modality in disease investigation and biomarker discovery. This dissertation focuses on the application of LC-MS/MS proteomic strategies to various human disease states, both benign and malignant. A basic workflow for simultaneous profiling of intracellular and extracellular proteomes using in vitro models was developed to probe cellular communication in the context of disease. When examining changes in a model of prostate cancer with therapeutic intervention, a senescent-like phenotype was observed, indicating a potential therapeutic avenue for pharmaceutical development. Additional studies centered on the development of a processing pipeline that integrates mass spectrometry imaging (MSI) with complementary LC-MS/MS data to improve identification confidence in MSI data and enable untargeted spatial profiling. This platform, named MSIght, was subsequently utilized alongside serum profiling to investigate the effects of estrogen receptor alpha inhibition in mouse models of lower urinary tract dysfunction (LUTD) associated with benign prostatic hyperplasia (BPH). Finally, an analysis of glycosylation in neuronal proteins - and their corresponding alterations - was performed in mouse models of fragile X syndrome (FXS), with a particular focus on the enrichment of synaptic glycoproteome alterations. This dissertation demonstrates the broad utility of MS-based proteomic strategies across diverse disease states and sample types, while also identifying and uncovering potential therapeutic avenues in each application.
일반주제명  
Pharmaceutical sciences
일반주제명  
Analytical chemistry
키워드  
Mass spectrometry
키워드  
Proteomics
키워드  
Liquid chromatography
키워드  
Extracellular proteomes
기타저자  
The University of Wisconsin - Madison Pharmaceutical Sciences
기본자료저록  
Dissertations Abstracts International. 86-12B.
전자적 위치 및 접속  
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■1001  ▼aMiles,  Hannah  Nicole.
■24510▼aMass  Spectrometry-Based  Proteomic  Investigations  Into  Human  Disease
■260    ▼a[Sl]▼bThe  University  of  Wisconsin  -  Madison▼c2025
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2025
■300    ▼a227  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  86-12,  Section:  B.
■500    ▼aAdvisor:  Li,  Lingjun;Ricke,  William  A.
■5021  ▼aThesis  (Ph.D.)--The  University  of  Wisconsin  -  Madison,  2025.
■520    ▼aMass  spectrometry  (MS)  has  become  a  powerful  tool  for  examining  human  disease,  offering  high  sensitivity  and  throughput  across  a  wide  range  of  analyte  classes.  Global  proteomic  profiling,  achieved  by  coupling  of  liquid  chromatography  (LC)  with  tandem  MS  scans,  commonly  referred  to  as  LC-MS/MS,  has  become  a  powerful  modality  in  disease  investigation  and  biomarker  discovery.  This  dissertation  focuses  on  the  application  of  LC-MS/MS  proteomic  strategies  to  various  human  disease  states,  both  benign  and  malignant.  A  basic  workflow  for  simultaneous  profiling  of  intracellular  and  extracellular  proteomes  using  in  vitro  models  was  developed  to  probe  cellular  communication  in  the  context  of  disease.  When  examining  changes  in  a  model  of  prostate  cancer  with  therapeutic  intervention,  a  senescent-like  phenotype  was  observed,  indicating  a  potential  therapeutic  avenue  for  pharmaceutical  development.  Additional  studies  centered  on  the  development  of  a  processing  pipeline  that  integrates  mass  spectrometry  imaging  (MSI)  with  complementary  LC-MS/MS  data  to  improve  identification  confidence  in  MSI  data  and  enable  untargeted  spatial  profiling.  This  platform,  named  MSIght,  was  subsequently  utilized  alongside  serum  profiling  to  investigate  the  effects  of  estrogen  receptor  alpha  inhibition  in  mouse  models  of  lower  urinary  tract  dysfunction  (LUTD)  associated  with  benign  prostatic  hyperplasia  (BPH).  Finally,  an  analysis  of  glycosylation  in  neuronal  proteins  -  and  their  corresponding  alterations  -  was  performed  in  mouse  models  of  fragile  X  syndrome  (FXS),  with  a  particular  focus  on  the  enrichment  of  synaptic  glycoproteome  alterations.  This  dissertation  demonstrates  the  broad  utility  of  MS-based  proteomic  strategies  across  diverse  disease  states  and  sample  types,  while  also  identifying  and  uncovering  potential  therapeutic  avenues  in  each  application.
■590    ▼aSchool  code:  0262.
■650  4▼aPharmaceutical  sciences
■650  4▼aAnalytical  chemistry
■653    ▼aMass  spectrometry
■653    ▼aProteomics
■653    ▼aLiquid  chromatography
■653    ▼aExtracellular  proteomes
■690    ▼a0572
■690    ▼a0486
■71020▼aThe  University  of  Wisconsin  -  Madison▼bPharmaceutical  Sciences.
■7730  ▼tDissertations  Abstracts  International▼g86-12B.
■790    ▼a0262
■791    ▼aPh.D.
■792    ▼a2025
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17358411▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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