Email: Click to Mail
Phone: (805) 893-2610
Fax: (805) 893-4731
Office Location: 3335 Engineering II
Address: Chemical Engineering,
Mail Code 5080,
University of California,
Santa Barbara, CA 93106-5080 USA
Lab Phone: (805) 893-3477
Name: Debbie Watts
Email: Click to Mail
Phone: (805) 893-8692
Fax: (805) 893-4731
BS: Chemical Engr. (Honors), University of Minnesota, Minneapolis-St. Paul (1993)
PhD: Chemical Engineering, The University of Texas at Austin (1999)
2010 Fellow, American Institute of Medical and Biological Engineering (AIMBE)
2007 ACS Young Investigator Award, Biochemical Technology Division
2006 Camille Dreyfus Teacher Scholar Award
2005 National Science Foundation CAREER Award
2005 Keynote Lecturer, FOSBE Meeting
2003 Santa Barbara Cottage Hospital Research Award
Proteolytic enzymes; specificity & redesign, imaging probes
Proteolytic enzymes play critical roles in diverse biologic processes in health and disease. Despite their recognized importance, little is known about where and when proteases are activated, and which substrates they act upon to carry out their biological functions. We are creating peptide-based probes that enable quantitative measurements of protease activity in living organisms. Using display technologies developed in the Daugherty Laboratory (bacterial display and CLiPS), we are designing and constructing novel activity-based detection probes to elucidate the functions of proteases involved in cancer progression. These probes may provide the first quantitative measurements that reveal where and when these critical enzymes are activated, and lead to new therapeutic strategies.
The ability of proteases to specifically activate or deactivate target protein substrates with high catalytic efficiency creates new therapeutic opportunities. However, the development of proteases as therapeutics is limited by our understanding of how protein structure confers high substrate selectivity. Thus, we are developing technologies to analyze millions of proteases variants to identify how specific amino acid substitutions and structural changes influence substrate specificity.
Antibody signatures of health and disease
The antibody repertoire in blood has proven to be a rich source of information to diagnose a range of diseases. Unique antibody reactivity patterns, or signatures, been observed for many different diseases (Cancer, autoimmune, neurodegenerative, and infectious). Even so, the identification of those few antibody species that indicate disease (i.e. antibody biomarkers) has proven remarkably challenging. We have developed a new antibody biomarker discovery method that provides a unique opportunity to discover diagnostically useful biomarkers for unmet medical needs. This method uses quantitative, specificity-based display library screening to identify and evolve peptide reagents that specifically capture disease-associated antibodies under clinically relevant conditions. With our clinical collaborators, we are refining and applying these methods to discover antibody-reagent pairs suitable for diagnostic development and clinical translation.
Therapeutic peptide design
Therapeutic peptides are a large and rapidly growing class of biological therapeutics. Given their small size and potential for high potency, peptides are well suited for alternative formulations and delivery routes. Using our peptide discovery tools, we are engineering small cyclic peptides specific for several therapeutic protein targets. The ability to rapidly discover and optimize key peptide properties (affinity, specificity, and stability) provides a potential route to develop next generation multifunctional therapeutics that exhibit improved safety and efficacy profiles.
Selected Recent Publications
Kenrick SA, Daugherty PS. Bacterial display enables efficient and quantitative peptide affinity maturation. Protein Eng Des Sel. 2010. 23(1):9-17. (Cover article)
Karim AY, Kulczycka M, Kantyka T, Dubin G, Jabaiah A, Daugherty PS, Thogersen IB, Enghild JJ, Nguyen KA, Potempa J. A novel matrix metalloprotease-like enzyme (karilysin) of the periodontal pathogen Tannerella forsythia ATCC 43037. Biol. Chem. 2010 391(1):105-17.
Boulware KT, Jabaiah AM, Daugherty PS. Evolutionary optimization of peptide substrates for proteases that exhibit rapid hydrolysis kinetics. Biotechnol. Bioeng. 2010. 106(3):339-46. (Featured article)
Nguyen, AW, You, X, Jabaiah, AM, Daugherty, PS. Fluorescent Protein FRET Applications: Protein Engineering, Intracellular Sensing, and Interaction Screening, Principles of Fluorescence Spectroscopy, Fluorescent Proteins and Their Uses. 2010 Vol. 12.
Xiao Y, Dane K, Uzawa T, Csordas A, Qian J, Soh T, Daugherty P, Lagally E; Heeger, A, Plaxco K. Detection of telomerase activity in high concentration of cell lysates using primer-modified gold nanoparticles. J Am Chem Soc. 2010.132(43):15299-15307.
Little, L, Dane KY, Daugherty PS, Healy K and Schaffer D. Exploiting bacterial peptide display technology to engineer biomaterials for neural stem cell culture. Biomaterials. 2011 32(6):1484-94.
Jabaiah AM, Daugherty PS. Directed evolution of protease beacons that enable sensitive detection of endogenous MT1-MMP activity in tumor cell lines. Chem. Biol. 2011. 25;18(3):392-401.
Getz JA, Rice JJ, Daugherty PS. Protease resistant peptide ligands from a knottin scaffold library. ACS Chemical Biology. 2011.19;6(8):837.
Getz JA, Schoep T, Daugherty PS. Peptide discovery using bacterial display and flow cytometry. Methods in Enzymology, Vol. 503, Burlington: Academic Press, 2012, pp. 75-97. ISBN: 978-0-12-396962-0.
Kalińska M, Kantyka T, Greenbaum DC, Larsen KS, Władyka B, Jabaiah A, Bogyo M, Daugherty PS, Wysocka M, Lesner A, Rolka A, Schaschke N, Stennicke H, Dubin A, Potempa J, Dubin G. Substrate specificity of Staphylococcus aureus cysteine proteases - Staphopains A, B and C Biochimie. 2012 Feb; 94(2):318-27.
Jabaiah, AM, Getz JA, Witkowski, WA, Hardy, JA, Daugherty, PS. Identification of protease exosite-interacting peptides that enhance substrate cleavage kinetics. Biol. Chem. 2012. 393(9):933-41.
Erster O, Thomas, JM, Hamza J, Schoep T, Jabaiah AM, Getz JA, Hall SS, Ruoslahti, E, Daugherty PS. Site-specific targeting of antibody activity in vivo mediated by disease-associated proteases. J Control Release. 2012 161(3):804-812.