Abstract/Details

Dissecting biological pathways in cancer and bacteria through the study and application of serine protease inhibitors


2011 2011

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Abstract (summary)

Serine proteases are an abundant class of enzymes that are vital to many biological processes. Proteolysis must be tightly controlled, and this regulation is frequently carried out through serine protease inhibitors. Dysregulation of either the protease or the inhibitor can have severe biological consequences, such as the development of cancer. Additionally, the role of proteases can be challenging to study, since the active form or proteases can be difficult to isolate. In this thesis, the role of the naturally occurring protease inhibitor PI-9 is examined in the development of prostate cancer. The findings presented here show that PI-9 protects prostate cancer cells from immunosurveillance early in cancer progression. Additionally, a chemical biology approach is taken to develop small molecule activity based probes for serine proteases, in order to better study active proteases in complex systems. Principles governing the design and potency of these probes were discovered, and new imaging applications for these probes were developed. These new techniques could be applied to the study of proteases in any biological system. The work described here provides new information on how to identify proteases involved in cancer and bacterial development, and such insights could be used to design new therapeutic strategies.

Indexing (details)


Subject
Microbiology;
Biochemistry;
Oncology
Classification
0410: Microbiology
0487: Biochemistry
0992: Oncology
Identifier / keyword
Health and environmental sciences; Pure sciences; Biological sciences; Activity-based probes; Granzyme b; Phosphonate; Prostate cancer; Protease inhibitors; Serpinb9
Title
Dissecting biological pathways in cancer and bacteria through the study and application of serine protease inhibitors
Author
Ray, Manisha
Number of pages
114
Publication year
2011
Degree date
2011
School code
0034
Source
DAI-B 73/01, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9781124922058
Advisor
Craik, Charles S.
Committee member
Cox, Jeffery S.; Gross, Carol A.
University/institution
University of California, San Francisco
Department
Biochemistry and Molecular Biology
University location
United States -- California
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3474958
ProQuest document ID
899268429
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/899268429
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