(6aw) Synergizing Engineering, Chemical, and Immunological Concepts to Design the Next Generation of Therapeutics for Unmet Clinical Needs

The overall focus of my research is to develop solutions for unmet clinical needs using engineering, biological, immunological, and chemical techniques. The overall vision is to combine identification of targeting ligands, nanoparticles, and immunologic stimulating payloads to generate therapeutics that allow for controlled activation of an immunologic response against a pathologic region of tissue. I have published manuscripts relating to all three components of this process and have experience with all phases of from design to preclinical validation. Additionally, combining synthetic chemical handles with proteins, separating accumulation and activation phases of pro-drugs, and tissue penetration are also major foci. Synergizing these interests into a single project allows for generation of novel solutions for current clinical needs that isn’t apparent by focusing on a single piece along the process of developing next generation therapeutics.

Research Experience:

I have experience identifying targeting ligands using multiple platforms including phage and yeast surface display, site-specific combination of biological and synthetic chemistry products, development of novel immunotherapies for cancer, and reducing adverse events associated with treatments. I have primarily focused on malignant disease including non-small cell lung cancer and glioblastoma multiforme brain cancer including a recent publication that exploited blood brain barrier (BBB) disruption, rather than disease-associated cellular receptors, to deliver therapeutics to neuropathologies. I also have experience with immunological assays, vaccines, peptide synthesis, liposome production, protein production, in vitro tissue culture models, and in vivo rodent models.

Teaching Interests:

Primarily interested in developing and equipping engineering students for the challenges they will encounter the dynamic field of engineering. While basic competencies are required to have a productive conversation, my interest is teaching abstract concepts such as problem solving, rationale decision making, optimization of resources, and interpersonal skills that are needed to succeed in almost any future position. Given the rapidly changing dynamic and the career mobility of current generations these ideas are essential to the success of future engineers.

Teaching Experience:

Mentored high school, undergraduate, and medical science training program (MSTP) students in the laboratory from diverse educational and cultural backgrounds. Lead a team of research technicians and taught group sessions for the first-year graduate students core course.

Future Directions:

My short-term goals are to combine engineering principles with physiologic targeting mechanisms to improve accumulation and penetration of targeting ligands in neuropathologies that exhibit blood brain barrier disruption as well as develop methods to separate the accumulation and activation phases of prodrug therapies. My long-term goals are to engineer delivery systems for precision delivery of therapeutics to biological tissues and develop scalable solutions to produce these platforms.

Selected Publications:

1. 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. (In Press, Science Advances)
2. Umlauf BJ, Mix KA, Grosskopf VA, Raines RT, Shusta EV. Site-Specific Antibody Functionalization Using Tetrazine-Styrene Cycloaddition. Bioconjug Chem. 2018 May 3.
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
4. 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
5. 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.