Honors & Awards
Phi Beta Kappa, University of Washington (2010)
iGEM Regional Championship Winner, International Genetically Engineered Machine Competition (2011)
iGEM World Championship Grand Prize, International Genetically Engineered Machine Competition (2011)
Mary Gates Research Scholarship, University of Washington (2012)
Department of Chemistry Award, University of Washington (2012)
Speaker at TedXYouth@Seattle, TedXYouth (2012)
Speaker at Women in Innovation Summit, WINS (2012)
Stanford Graduate Fellowship, Stanford University (2013)
NSF Graduate Fellowship, Honorable Mention, National Science Foundation (2014)
NSF Graduate Fellowship, Honorable Mention, National Science Foundation (2015)
Education & Certifications
Bachelor of Science, University of Washington, Biochemistry (2012)
Irving Weissman, Doctoral Dissertation Advisor (AC)
Aaron Ring, Andrew Kruse, Aashish Manglik, Irv Weissman, Roy Maute, Melissa McCracken, Sydney Gordon. "United States Patent 14/821,589 High Affinity PD-1 Agents and Methods of Use", Leland Stanford Junior University, Aug 7, 2015
Justin SIEGEL, David BAKER, Sydney GORDON, Rin Anna, Ingrid PULTZ, Elizabeth STANLEY, Sarah WOLF. "United States Patent 2013023151 COMPOSITIONS AND METHODS FOR TREATING CELIAC SPRUE DISEASE", University of Washington, Feb 15, 2013
Current Research and Scholarly Interests
Engineering and development of small protein cancer immunotherapeutics.
- Engineering high-affinity PD-1 variants for optimized immunotherapy and immuno-PET imaging PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2015; 112 (47): E6506-E6514
Computational Design of an alpha-Gliadin Peptidase
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2012; 134 (50): 20513-20520
The ability to rationally modify enzymes to perform novel chemical transformations is essential for the rapid production of next-generation protein therapeutics. Here we describe the use of chemical principles to identify a naturally occurring acid-active peptidase, and the subsequent use of computational protein design tools to reengineer its specificity toward immunogenic elements found in gluten that are the proposed cause of celiac disease. The engineered enzyme exhibits a k(cat)/K(M) of 568 M(-1) s(-1), representing a 116-fold greater proteolytic activity for a model gluten tetrapeptide than the native template enzyme, as well as an over 800-fold switch in substrate specificity toward immunogenic portions of gluten peptides. The computationally engineered enzyme is resistant to proteolysis by digestive proteases and degrades over 95% of an immunogenic peptide implicated in celiac disease in under an hour. Thus, through identification of a natural enzyme with the pre-existing qualities relevant to an ultimate goal and redefinition of its substrate specificity using computational modeling, we were able to generate an enzyme with potential as a therapeutic for celiac disease.
View details for DOI 10.1021/03094795
View details for Web of Science ID 000312430700051
View details for PubMedID 23153249
Hematopoietic stem cell transplantation in immunocompetent hosts without radiation or chemotherapy.
Science translational medicine
2016; 8 (351): 351ra105-?
Hematopoietic stem cell (HSC) transplantation can cure diverse diseases of the blood system, including hematologic malignancies, anemias, and autoimmune disorders. However, patients must undergo toxic conditioning regimens that use chemotherapy and/or radiation to eliminate host HSCs and enable donor HSC engraftment. Previous studies have shown that anti-c-Kit monoclonal antibodies deplete HSCs from bone marrow niches, allowing donor HSC engraftment in immunodeficient mice. We show that host HSC clearance is dependent on Fc-mediated antibody effector functions, and enhancing effector activity through blockade of CD47, a myeloid-specific immune checkpoint, extends anti-c-Kit conditioning to fully immunocompetent mice. The combined treatment leads to elimination of >99% of host HSCs and robust multilineage blood reconstitution after HSC transplantation. This targeted conditioning regimen that uses only biologic agents has the potential to transform the practice of HSC transplantation and enable its use in a wider spectrum of patients.
View details for DOI 10.1126/scitranslmed.aae0501
View details for PubMedID 27510901