Cassandra Callmann, Ph.D.

American Cancer Society Postdoctoral Fellow

Research Overview

Hijacking Nature’s Own Molecules and Pathways to Understand and Treat Disease

My research background and interests are centered on elucidating the effect of chemical structure and hierarchical arrangement of biohybrid supramolecular assemblies (peptide-, lipid-, nucleic acid-, and carbohydrate-based) on their interactions with biological systems, as well as developing ways to hijack or modulate these dynamic interactions to achieve highly specified and targeted cargo delivery.

Spherical Nucleic Acids for Cancer Immunotherapy

Spherical nucleic acids (SNAs) are chemically well-defined nanoscale structures comprised of nucleic acids densely arranged around a spherical nanoparticle core in a highly oriented fashion. When comprised of immunostimulatory nucleic acids together with cancer-associated proteins or peptides, SNAs efficiently mobilize the immune system to seek and destroy tumors. The chemical composition of these materials, as well as the way they are arranged on the nanoscale, has a profound impact on the efficacy of SNA-based immunotherapeutics.

Long Chain Fatty Acid Mimics for Hitchhiking on Serum Albumin

Human Serum Albumin (HSA) is the most abundant serum protein and a main transporter of long chain fatty acids (LCFAs) throughout the body. Mimicking this interaction using an 18 carbon α,ω-dicarboxylic acid mono-functionalized with paclitaxel via ester linkage affords a prodrug that forms strong, stable electrostatic interactions with HSA in its natural binding sites for LCFAs. This material binds to HSA with higher affinity than stearic acid and shows differentiated pharmacokinetics, as well as remarkable tolerability and efficacy in multiple tumor xenograft models. Moreover, this motif is generalizable to multiple diverse classes of therapeutic and diagnostic cargo.

Peptide-Polymer Amphiphiles for Targeted Drug Delivery to Tumors

Matrix metalloproteinases (MMPs) are highly overexpressed in the extracellular matrix (ECM) of many aggressive tumors. Polymerizing hydrophilic peptides that are natural substrates for MMPs, together with hydrophobic drug molecules using living graft-through polymerization, affords peptide-polymer amphiphiles (PPAs) that assemble into ~30 nm nanoparticles. Following intravenous injection, these materials undergo drastic changes in morphology when exposed to MMPs in the tumor ECM and are retained in tumor tissue for prolonged, local drug release.

Carbohydrate-Polymer Conjugates for Understanding and Modulating Biological Interactions

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©2020 by Cassandra Callmann, Ph.D.