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Cellular Consequences of Dynamic Receptor Tyrosine Kinase Signaling
Cellular Consequences of Dynamic Receptor Tyrosine Kinase Signaling
Cellular Consequences of Dynamic Receptor Tyrosine Kinase Signaling

Detailed Information

자료유형  
 학위논문 서양
최종처리일시  
20260202103000
ISBN  
9798280749252
DDC  
574
저자명  
Thornton, Richard H.
서명/저자  
Cellular Consequences of Dynamic Receptor Tyrosine Kinase Signaling
발행사항  
[Sl] : Princeton University, 2025
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2025
형태사항  
106 p
주기사항  
Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
주기사항  
Advisor: Toettcher, Jared E. .
학위논문주기  
Thesis (Ph.D.)--Princeton University, 2025.
초록/해제  
요약Communication via signal transduction is the foundation of how multicellular organisms interact with the external environment and how they relay internal information. Seeking to understand how these signals are conveyed is a prime directive for many branches of science, with many disease states originating from signal dysregulation. In addition to preventing undesirable outcomes, enhanced comprehension of how cells transmit information can also aid in characterizing developmental and regenerative processes. While signaling networks are composed of many important members, this work centers on receptor tyrosine kinases (RTKs) and their targets since they are well-studied and integral to many biological functions. Many cues transmitted via these membrane-embedded enzymes orchestrate information flow through dynamic methods, including spatiotemporal variation (Chapter 1). The work presented in this thesis focuses on several key areas relating to RTK-based signaling and time-variable activity. Chapter 2 is dedicated to the construction and implementation of a migration assay that utilizes optogenetic control of EGFR to precisely direct tissues in a variety of geometries and inhibitory conditions. By characterizing multiple cell types with this method, we were able to craft the foundations of a more generalizable model for epithelial tissue migration. Chapter 3 focuses on how altered signaling activity correlates to drug resistant phenotypes in cancer models. With the implementation of biosensors that report/record pulsatile Erk activity during and after drug adaptation discernable changes in signal patterns were observed, corroborating previous work in the field. Finally, Chapter 4 summarizes the findings for each chapter and details how future work can effectively utilize this dissertation to develop clinically-relevant optogenetic wound healing and craft a protocol for screening oncogenic drug resistance based on signaling state.
일반주제명  
Molecular biology
일반주제명  
Bioengineering
일반주제명  
Cellular biology
일반주제명  
Biomedical engineering
키워드  
Dynamics
키워드  
Kinases
키워드  
Migration
키워드  
Optogenetics
키워드  
Receptor
키워드  
Signaling activity
기타저자  
Princeton University Molecular Biology
기본자료저록  
Dissertations Abstracts International. 86-12B.
전자적 위치 및 접속  
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MARC

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■040    ▼aMiAaPQ▼cMiAaPQ
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■1001  ▼aThornton,  Richard  H.▼0(orcid)0000-0002-9707-6110
■24510▼aCellular  Consequences  of  Dynamic  Receptor  Tyrosine  Kinase  Signaling
■260    ▼a[Sl]▼bPrinceton  University▼c2025
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2025
■300    ▼a106  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  86-12,  Section:  B.
■500    ▼aAdvisor:  Toettcher,  Jared  E.  .
■5021  ▼aThesis  (Ph.D.)--Princeton  University,  2025.
■520    ▼aCommunication  via  signal  transduction  is  the  foundation  of  how  multicellular  organisms  interact  with  the  external  environment  and  how  they  relay  internal  information.  Seeking  to  understand  how  these  signals  are  conveyed  is  a  prime  directive  for  many  branches  of  science,  with  many  disease  states  originating  from  signal  dysregulation.  In  addition  to  preventing  undesirable  outcomes,  enhanced  comprehension  of  how  cells  transmit  information  can  also  aid  in  characterizing  developmental  and  regenerative  processes.  While  signaling  networks  are  composed  of  many  important  members,  this  work  centers  on  receptor  tyrosine  kinases  (RTKs)  and  their  targets  since  they  are  well-studied  and  integral  to  many  biological  functions.  Many  cues  transmitted  via  these  membrane-embedded  enzymes  orchestrate  information  flow  through  dynamic  methods,  including  spatiotemporal  variation  (Chapter  1).  The  work  presented  in  this  thesis  focuses  on  several  key  areas  relating  to  RTK-based  signaling  and  time-variable  activity.  Chapter  2  is  dedicated  to  the  construction  and  implementation  of  a  migration  assay  that  utilizes  optogenetic  control  of  EGFR  to  precisely  direct  tissues  in  a  variety  of  geometries  and  inhibitory  conditions.  By  characterizing  multiple  cell  types  with  this  method,  we  were  able  to  craft  the  foundations  of  a  more  generalizable  model  for  epithelial  tissue  migration.  Chapter  3  focuses  on  how  altered  signaling  activity  correlates  to  drug  resistant  phenotypes  in  cancer  models.  With  the  implementation  of  biosensors  that  report/record  pulsatile  Erk  activity  during  and  after  drug  adaptation  discernable  changes  in  signal  patterns  were  observed,  corroborating  previous  work  in  the  field.  Finally,  Chapter  4  summarizes  the  findings  for  each  chapter  and  details  how  future  work  can  effectively  utilize  this  dissertation  to  develop  clinically-relevant  optogenetic  wound  healing  and  craft  a  protocol  for  screening  oncogenic  drug  resistance  based  on  signaling  state.
■590    ▼aSchool  code:  0181.
■650  4▼aMolecular  biology
■650  4▼aBioengineering
■650  4▼aCellular  biology
■650  4▼aBiomedical  engineering
■653    ▼aDynamics
■653    ▼aKinases
■653    ▼aMigration
■653    ▼aOptogenetics
■653    ▼aReceptor
■653    ▼aSignaling  activity  
■690    ▼a0307
■690    ▼a0202
■690    ▼a0379
■690    ▼a0541
■71020▼aPrinceton  University▼bMolecular  Biology.
■7730  ▼tDissertations  Abstracts  International▼g86-12B.
■790    ▼a0181
■791    ▼aPh.D.
■792    ▼a2025
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17356598▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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