"STRUCTURAL BIOLOGY OF DIAPHANOUS-1 AND ITS ROLE IN HUMAN PATHOLOGY" by Gregory G. Theophall

ORCID

0000-0001-7515-2998

Date of Award

Fall 2024

Language

English

Embargo Period

12-3-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Chemistry

Program

Chemistry

First Advisor

Alxander Shekhtman

Committee Members

Alexander Shekhtman, Igor Lednev, Li Niu, Maxim Royzen, Ravichadran Ramasamay

Keywords

DIAPH1, RAGE, RHO, DIABETES, CARDIOVASCULAR DISEASE, INFLAMMATION

Subject Categories

Chemistry

Abstract

DIAPH1 is diaphanous related formin which polymerizes actin into filaments and is important to cytoskeleton dynamics.[1, 2] The dysregulation and aberrant activation of DIAPH1 is known to cause deafness[3, 4] and clotting disorders,[5] and is recently implicated in the inflammatory responses associated with cardiovascular and diabetic pathology.[6-9] Despite this, activation of the full length structure and its regulation are poorly understood.[10-12] Therefore, the main objective of this dissertation is to explore the structural, autoinhibitory, and regulatory properties of DIAPH1 in the context of disease pathology. Herein, I show that DIAPH1 has a dynamic structure which is regulated through negative cooperativity, and describe the structural interactions with proteins involved in inflammatory responses.

Comments

There is a 1 year embargo on this dissertation

License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Available for download on Wednesday, December 03, 2025

Included in

Chemistry Commons

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