Date: Tuesday, January 14, 2020
Time: 11:00 am
Talk Title: Macromolecular Therapeutics: New Class of Broadly Applicable Biologics
Location: Chemla Room (67-3111)
Biography:
Our program approaches a set of clustered problems of fundamental and therapeutic interest. For example, the discovery and refinement of antibiotics was one of the crowning achievements in the 20th century that revolutionized healthcare treatment. If properly dosed, they could eradicate infection. Unfortunately, this therapeutic specificity of antibiotics also leads to their undoing as under-dosing (incomplete kill) allows for minor mutative changes that mitigate the effect of the antibiotic leading to resistance development. The pervasiveness of drug-resistant infections is a global health issue with significant healthcare, economic and societal burdens. A similar situation exist in cancer treatments, where multiple chemotherapeutics and chemosensitizers are required to mitigate resistance and loss of efficacy. We have developed numerous platform technologies based on rationally designed macromolecules that address key issues in multi-drug resistant diseases including cancer as well as bacterial, and viral infections. Supramolecular structures were developed for cancer therapy that target both cancer cells and cancer stem cells, mitigate drug resistance, and metastasis. Membrane-disruptive macromolecular antimicrobials for treatment of infections were demonstrated in vitro and in vivo, and shown to have efficacy and selectivity against multidrug-resistant A. baumannii and MRSA without inducing toxicity. We have demonstrated a general and broad-spectrum strategy to prevent viral infections using multi-functional macromolecules that inhibit viruses such as influenza, Zika, Ebola, and HBV. In each case, the dynamic nature of the non-covalent hydrogen bonding and ionic interactions allows these polymers to co-evolve concurrently with the disease, thereby preventing resistance without loss in effectiveness.
