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College of Arts and Sciences Department of Chemistry

Organic Chemistry Proposal Seminar – Aaron Hendricksen

Oral Prelim Exam Announcement

Tuesday, November 3rd @ 12:30 pm; ZOOM ONLY

Aaron Hendricksen (Mancini Group)

Title: Multivalent Immunostimulant Glycopolymers as Novel Adjuvants and Immunotherapeutics

 Abstract: The development of rationally designed adjuvants is critical for the efficacy of purified antigens used in modern vaccine formulations including those developed for cancer immunotherapy. Few adjuvants are licensed for use in human vaccines at this time, however recent advances in the understanding of immune activation allow for development of discrete motifs targeting Pattern Recognition Receptors (PRRs) to the desired clinical benefit. Of these PRRs, the Macrophage Inducible C-Type Lectin receptor (MINCLE) has become an attractive target for adjuvant design. Despite this, only one experimental adjuvant CAF01 has been formulated for human use with trehalose dibehenate, a synthetic analogue of the glycolipid responsible for pathogenicity of Mycobacterium tuberculosis, whereby multivalent agonism is exploited for effective signaling. Furthermore, aryl derivatives of trehalose including the natural product brartemicin have demonstrated anti-invasive properties by inhibition of key proteins involved in tumor metathesis, highlighting the promising role of C-type lectin receptor agonists as anti-cancer therapeutics. In this work, we will investigate the molecular parameters for multivalent MINCLE agonism with a trehalose-based glycopolymer scaffold constructed via controlled/living radical polymerization for precise control of agonist density and macromolecular architecture.  In addition, we propose the development of a hydrophilic tri-block polymer scaffold that retains MINCLE-specific immunogenicity and expands the platform to include aryl trehalose subunits for application in cancer immunotherapy. We propose a hydrophilic A-block for improved solubility and passive targeting of tumor tissue, a lipidated trehalose B-block to exploit multivalent MINCLE agonism, and an aryl trehalose C-block for delivery of anti-invasive therapeutics to the tumor microenvironment. The proposed work will elucidate the discrete molecular parameters of multivalent agonism for improvement of adjuvant design and subsequent control of immune response, while combined properties of MINCLE dependent immunogenicity and metathesis inhibition in tandem with the in vivo benefits of macromolecular carriers will serve to broaden their potential in cancer immunotherapy.

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Date & Time: Nov 3, 2020 12:30 PM Pacific Time (US and Canada)

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Organic Seminar-Emily Savoy (Berkman)

Title: Development of a Urine-Based Liquid Biopsy for Prostate Cancer

Emily Savoy (Berkman Group)

Abstract: A urine-based liquid biopsy is a non-invasive approach to detect validated biomarkers for the evaluation or diagnosis of prostate cancer. Extracellular vesicles (EVs) have received significant attention for their role in cell-cell communication and are currently being explored as a tool for prognostic and diagnostic management. Consequently, various exosome isolation methods, based on different principles, have been developed. The important enzyme biomarker Prostate Specific Membrane Antigen, PSMA, is a validated target for prostate cancer and is also expressed on tumor-derived exosomes. Tumor secreted exosomes could be used as an extracellular resource of PSMA and thus, as a simple and effective non-invasive approach to detect prostate cancer. By using a PSMA inhibitor magnetic isolation system, there is the potential to rapidly capture and quantify progression of prostate cancer. In this presentation, inhibitor synthesis and various exosome isolation methods will be discussed. Future work includes the nondestructive capture and characterization of tumor-derived exosomes through a variety of exosome isolation methods.