Dissertations, Theses, and Capstone Projects

Date of Degree

9-2023

Document Type

Dissertation

Degree Name

Ph.D.

Program

Chemistry

Advisor

Sanjai Kumar Pathak

Committee Members

Susan Rotenberg

Sonia Melino

Shi Jin

Yu Chen

Abstract

Proteases, specifically cysteine proteases, are crucial for the survival and growth of living organisms. They hydrolyze proteins and use different mechanisms to function. Cysteine proteases are classified into three types: papain, caspase, and picornaviridae. The papain class, with 11 cysteine cathepsins, regulates essential physiological functions, and abnormal expression is linked to various diseases. Our research aims to develop small molecules that inhibit cathepsins B and L to develop probes for functional proteomics.

The centrosome is critical for proper cell division and is regulated by multiple kinases, including Nek2. Nek2 is highly concentrated at the centrosome in vertebrates and plays a critical role in maintaining and modifying its architecture. Nek2 kinase activity promotes the splitting of duplicated centrosomes at the beginning of mitosis. Abnormalities in centrosome structure can lead to chromosomal instability, aneuploidy, and cancer. Inhibition of Nek2 offers hope for anti - cancer drug development, as Nek2 expression is high in several types of highly metastatic cancers.

This work is embargoed and will be available for download on Tuesday, September 30, 2025

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