Targeting Neuropathologies via Blood-Brain Barrier (BBB) Disruption: We are interested in targeting therapies to neuropathologies via physiological disruption of the BBB that underlies many neurological diseases, in contrast to the current paradigm of targeting disease-associated cellular receptors. We previously published a study demonstrating targeting ligands that bind neural extracellular matrix preferentially hone to sites of chemically and glioblastoma induced BBB disruption (Science Adv. 2019 May 15;5(5):eaau4245).

Developing Peptide-Based Immunotherapies: We are interesting in developing peptide-based immunotherapies where immunogenic peptides are specifically targeted to cancer cells and presented in HLA class 1 receptors. In patients previously vaccinated against the immunogenic peptide, a robust cytotoxic T cell immune response is mounted against the tumor. We previously demonstrated proof-of-principle for the peptide-based immunotherapy concept using an autophagy mediated mechanism to facilitate presentation of the immunogenic peptide in HLA class 1 receptors of non-small cell lung cancer (NSCLC) tumors (Mol Ther. 2015 Jun;23(6):1092-1102).

Site-Specific Protein Modification: We are interested in developing methods for site-specific modification of proteins that allows for appending chemical handles precisely onto the c or n terminus of a protein to preserve the activity of the labelled protein. We have utilized express protein ligation (EPL) methods to specifically modify the c-terminus of antibody fragments with small molecules and fluorophores without altering antigen binding activity (Bioconjug Chem. 2018 May 16;29(5):1605-1613, Methods Mol Biol. 2020;2133:221-233).

Identifying Targeting Ligands: We are interested in identifying targeting ligands using selection-based assays. We have isolated targeting: peptides, scFvs, and VLRs (Variable Lymphocyte Receptors, the antigen recognition system from lamprey) using phage display and yeast surface display (YSD) libraries (Science Adv. 2019 May 15;5(5):eaau4245).

Full Bibliography

• Umlauf BJ, Shusta EV. Site-Directed Modification of Yeast-Produced Proteins Using Expressed Protein Ligation. Methods Mol Biol. 2020 2133:221-233.
• Umlauf BJ, Clark PA, Lajoie JM, Georgieva JV, Bremner S, Herrin BR, Kuo JS, Shusta EV. Identification of Variable Lymphocyte Receptors that can Target Therapeutics to Pathologically Exposed Brain Extracellular Matrix. Science Advances 2019 May;5(5):eaau4245
• Umlauf BJ, Shusta EV. Exploiting BBB Disruption for the Delivery of Nanocarriers to the Diseased CNS. Curr Opin Biotechnol. 2019 Mar 5;60:146-152

• Umlauf BJ, Mix KA, Grosskopf VA, Raines RT, Shusta EV. Site-Specific Antibody Functionalization Using Tetrazine-Styrene Cycloaddition. Bioconjug Chem. 2018 May 3.
• Zorniak M, Clark PA, Umlauf BJ, Cho Y, Shusta EV, Kuo JS. Yeast display biopanning identified human antibodies targeting glioblastoma stem-like cells. Scientific Rep. 2017 Nov 20;7(1):15840
• Umlauf BJ, Chung CY, Brown KC. Modular Three-Component Delivery System Facilitates HLA Class I Antigen Presentation and CD8+ T cell Activation Against Tumors. Mol Ther. 2015 Jun;23(6):1092-1102
• Umlauf BJ, McGuire MJ, Brown KC. Introduction of plasmid encoding for rare tRNAs reduces amplification bias in phage display biopanning. Biotechniques. 2015 Feb 1;58(2):81-4.
• Umlauf BJ, Mercedes JS, Chung CY, Brown KC. Identification of a Novel Lysosomal Trafficking Peptide using Phage Display Biopanning Coupled with Endocytic Selection Pressure. Bioconjug Chem. 2014 Oct 15;25(10):1829-37.
• Umlauf BJ, Haralambieva IH, Ovsyannikova IG, Kennedy RB, Pankratz VS, Jacobson RM, Poland GA: Associations between Demographic Variables and Multiple Measles-Specific Innate and Cell-Mediated Immune Responses Following Measles Vaccination, Viral Immunol. 2012 Feb;25(1):29-36
• Umlauf BJ, Pinsky NP, Ovsyannikova IG, Poland GA: Detection of vaccinia virus-specific IFNγ and IL-10 secretion from human PBMCs and CD8⁺ T cells by ELISPOT, Methods Mol Biol. 2012;792:199-218.
• Haralambieva IH, Ovsyannikova IG, Umlauf BJ, Vierkant RA, Shane Pankratz V, Jacobson RM, Poland GA: Genetic polymorphisms in host antiviral genes: Associations with humoral and cellular immunity to measles vaccine, Vaccine. 2011 Nov 8;29(48):8988-97.
• Umlauf BJ, Ovsyannikova IG, Haralambieva IH, Kennedy RB, Vierkant RA, Pankratz VS, Jacobson RM, Poland GA: Correlations between vaccinia-specific immune responses within a cohort of armed forces members, Viral Immunol. 2011 Oct;24(5):415-20.