Classes Taught
- Organic Chemistry
- Biochemistry
- Chemical Biology
- Medicinal Chemistry
- Drugs and Toxicology
- Nutrition
- Masters-level Medicinal Chemistry
Research InterestsResearch in Dr. Karver's lab broadly focuses on the chemical biology, bioorganic, and medicinal chemistry of inflammatory caspases. Specifically, we are developing chemical tools to study these enzymes. These enzymes are overactive in many inflammatory and autoimmune diseases which makes them potential drug targets. One set of projects is to create a structure-activity relationship (SAR) profile of successful and potent inhibitors of caspase-1, -4, and -5. Libraries of small molecules are synthesized and tested as inhibitors of caspases to create this profile. The biochemical testing uses commercially available fluorogenic peptides substrates.
A second set of projects aims to find selective peptide substrates for each caspase using a different fluorescence-based assay, Förster resonance energy transfer (FRET), developed in our lab in collaboration with Dr. Carey Southern in our department. Substrates are spectroscopically characterized prior to use in kinetics experiments. Kinetic progress curves and Michaelis-Menten kinetics parameters are used to compare the activity of each substrate with all of the caspases tested. A specificity profile for each enzyme will be developed to aid in creating a selective substrate for each inflammatory caspase.
Select Publications
- Amanda East, Callista G. Polasek, Elizabeth A. Miller, Srirajkumar Ranganathan, Isabella D. Reda, Aisha Patel, Christopher D. Ahlers, Sarah K. Zigngales, and Caitlin E. Karver* “Expansion of the structure-activity relationship profile of triaminopyrimidines as inhibitors of caspase-1” Accepted in revisions Chemical Biology and Drug Design 2024
- Kyle A. Grice*, Zoe M. Varsbergs, Yingjie Zhang, Sarah Zingales, Adam R. Johnson, Roger D. Sommer, Caitlin E. Karver* “Structural, computational, docking and biological studies of a triaminopyrimidine caspase-1 inhibitor” J. Mol. Struct, 2024, 1318, 139297
- Raj Ranganathan, Gena Lenti, Nicholas M. Tassone, Brian J. Scannell, Cathrine A. Southern, Caitlin E. Karver* “Design and Application of a Fluorogenic Assay for Monitoring Inflammatory Caspase Activity” Analytical Biochemistry, 2018, 543, 1-7
- Courtney R. Kent, Magdalena Bryja, Helen A. Gustafson, Margaret Y. Kawarski, Gena Lenti, Emily N. Thayer, Rachel C. Knopp, Victor Ceja, Bhabna Pati, D. Eric Walters and Caitlin E. Karver* “Variation of the aryl substituent on the piperazine ring within the 4-(piperazin-1-yl)-2,6-di(pyrrolidin-1-yl)pyrimidine scaffold unveils potent, non-competitive inhibitors of the inflammatory caspases” Bioorganic and Medicinal Chemistry Letters 2016, 26, 5476-5480.
- Sophia G. Robinson, Philip T. Burns, Amanda M. Miceli, Kyle A. Grice, Caitlin E. Karver, and Lihua Jin “Calorimetric Studies of the Interaction of Metalloenzyme Active Site Mimetics with Zinc-binding Inhibitors” Dalton Transactions, 2016, 45, 11817 – 11829.
- Margaret Kawarski, UThomas K. Hagerman and Caitlin E. Karver* “Lazaroids U83836E and U74389G are Potent, Time-dependent Inhibitors of Caspase-1” Chemical Biology and Drug Design 2015, 86, 1049-1054.
Service and Professional Activities
- Academic Program Review Committee
- Grade Challenge Review Board
- CSH Advising Committee
- CSH Exceptions Committee
- CSH Pre-health Advising Committee
- Health Sciences Faculty Council
- Organic Chemistry Committee
- Chair of Advising Committee
- Assessment Committee
- Graduate Committee
- Curriculum Committee
Professional Society Memberships
- American Chemical Society (ACS)
- International Society for Chemical Biology