Despite intense research efforts, therapeutic efficacies in multiple cancer types are sorely lacking. However, early detection of tumor formation can substantially improve patient prognosis via reduced probability of metastasis, improved therapeutic effectiveness, and reduced tumor burden. Our research applies engineering principles to chemistry, biology, and physiology to enhance the limits of disease detection, with a particular focus on in vivo molecular imaging of tumors. Molecular imaging is the non-invasive detection, localization, and quantification of molecules and molecular processes in the body. This approach can yield increased specificity and sensitivity relative to traditional imaging and enable a molecular understanding of disease biology thereby providing utility for diagnostics, therapeutic monitoring, drug development, and scientific research.
Imaging living systems at the molecular and cellular scale necessitates command of molecular recognition, molecular biology of the target, biological transport at the tissue and cellular levels, and detection technology. Our program benefits from focused research on high-throughput engineering of molecular recognition proteins with exceptional affinity, stability, and biological properties. This is coupled with in silico, in vitro, and in vivo studies of the biology and transport of the molecular target to yield efficient, selective delivery. These innovations are merged with multimodality imaging technologies to enhance detection. Tangentially, lessons learned in these endeavors are also directly applicable to (a) engineering proteins for industrial, scientific, and therapeutic applications; (b) in vitro diagnostics; (c) tumor targeting for therapeutic applications; and (d) targeting of other malignancies or molecules of scientific interest.
- Institute for Engineering in Medicine Faculty Career Development Award
- College of Science and Engineering Guillermo Borja Career Development Award
- Kim, M., Haman, K.J., Houang, E.M., Zhang, W., Yannopoulos, D., Metzger, J.M., Bates, F.S., Hackel, B. "PEO–PPO Diblock Copolymers Protect Myoblasts from Hypo-Osmotic Stress In Vitro Dependent on Copolymer Size, Composition, and Architecture" Biomacromolecules. 2017.
- Chan, J.Y., Hackel, B., Yee, D. "Targeting insulin receptor in breast cancer using small engineered protein scaffolds" Mol. Cancer. Ther. 2017.
- Stern, L., Csizmar, C., Woldring, D., Wagner, C., Hackel, B. "Titratable Avidity Reduction Enhances Affinity Discrimination in Mammalian Cellular Selections of Yeast-Displayed Ligands" ACS. Comb. Sci. 2017.
- Woldring, D., Holec, P., Stern, L., Du, Y., Hackel, B. "A Gradient of Sitewise Diversity Promotes Evolutionary Fitness for Binder Discovery in a Three-Helix Bundle Protein Scaffold" Biochem. 2017 56: 1656-1671.
- Johnson, S., Javner, C., Hackel, B. "Development and implementation of a protein-protein binding experiment to teach intermolecular interactions in high school or undergraduate classrooms" J. Chem. Ed. 2017 94: 367-374.
- Kruziki, M., Case, B., Chan, J., Zudock, E., Woldring, D., Yee, D., and Hackel, B.J., "64Cu-Labeled Gp2 Domain for PET Imaging of Epidermal Growth Factor Receptor" Mol. Pharm. 2016 13: 3747-3755.
- Holec, P.V., and Hackel, B.J., "PyMOL360: Multi-user gamepad control of molecular visualization software" J. Comput. Chem. 2016 37(30) 2667-69.
- Stern, L.A., Schrack, I.A., Johnson, S.M., Deshpande, A., Bennett, N.R., Harasymiw, L.A., Gardner, M.K., Hackel, B.J., "Geometry and expression enhance enrichment of functional yeast-displayed ligands via cell panning." Biotechnol. Bioeng. 2016 113:2328-41.
- Woldring, D.R., Holec, P.V., and Hackel, B.J., "ScaffoldSeq: Software for characterization of directed evolution populations" Proteins. 2016 84:869-74.
- Case, B.A., and Hackel, B.J., "Synthetic and natural consensus design for engineering charge within an affibody targeting epidermal growth factor receptor" Biotechnol. Bioeng. 2016 113:1628-38.
- Woldring, D.R., Holec, P.V., Zhou, H., and Hackel, B.J., "High-throughput ligand discovery reveals a sitewise gradient of diversity in broadly evolved hydrophilic fibronectin domains" PLOS One. 2015, 10, e0138956.
- McClintock, M., Kaznessis, Y.N., and Hackel B.J., "Enterocin A mutants identified by saturation mutagenesis enhance potency towards vancomycin-resistant Enterococci" Biotechnol. Bioeng. 2015.
- Kruziki, M.A., Bhatnagar, S., Woldring, D.R., Duong, V.T., and Hackel B.J., "A 45-amino acid scaffold mined from the Protein Data Bank for high affinity ligand engineering" Chem. Biol. 2015 22:946-956.