자료유형  

 학위논문

Control Number  

0017162143

International Standard Book Number  

9798383567654

Dewey Decimal Classification Number  

574

Main Entry-Personal Name  

Homan, Rick A.

Publication, Distribution, etc. (Imprint  

[S.l.] : The Scripps Research Institute., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

271 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-01, Section: B.

General Note  

Includes supplementary digital materials.

General Note  

Advisor: Parker, Christopher G.

Dissertation Note  

Thesis (Ph.D.)--The Scripps Research Institute, 2024.

Summary, Etc.  

요약Heme is a ubiquitously expressed small molecule modulator of protein function that participates in enzymatic reactions as a prosthetic group and acts as a signaling molecule to coordinate several facets of metabolism. Upon cellular damage, unbound "free" heme is released from cells and the heme binding proteins they contain, leading to oxidative damage of cellular components and activating inflammatory signals, serving as a damage-associated molecular pattern. In this context, free heme plays a pivotal role in pathological mechanisms of sterile and pathogenic hemolytic conditions, such as malaria, hemolytic anemias, and injury causing hemorrhage. Heme has been speculated to stimulate immune cells such as leukocytes through activation of precise signaling pathways via direct binding to innate immune receptors. However, the mechanisms by which heme causes the activation of pro-inflammatory responses is not fully understood. This is due to a lack of available tools to study transient heme-protein interactions in native systems. Here, we describe a strategy which utilizes a heme-based photoaffinity probe integrated with chemical proteomic methods to map heme-protein interactions across the proteome. We aim to elucidate specific proteins and biochemical pathways involved in the regulation of heme-dependent signaling functions in immune cells and ascertain the functional consequences and roles of identified immunomodulatory proteins in heme-induced signaling; we highlight examples such as CD36, a heme binding protein identified herein and annotated multifunctional scavenger receptor involved in pattern recognition and activation of immune cells and IRAK1, a pro-inflammatory signaling kinase which serves as a critical signaling node in toll-like receptor-mediated pattern recognition and inflammation.

Subject Added Entry-Topical Term  

Biochemistry.

Subject Added Entry-Topical Term  

Cellular biology.

Subject Added Entry-Topical Term  

Immunology.

Index Term-Uncontrolled  

Enzymatic reactions

Index Term-Uncontrolled  

Pathogenic hemolytic conditions

Index Term-Uncontrolled  

Immune cells

Index Term-Uncontrolled  

Hemolytic anemias

Index Term-Uncontrolled  

Biochemical pathways

Added Entry-Corporate Name  

The Scripps Research Institute Chemical Biology

Host Item Entry  

Dissertations Abstracts International. 86-01B.

Electronic Location and Access  

로그인을 한후 보실 수 있는 자료입니다.

Control Number  

joongbu:658558