The Medina group employs a multidisciplinary approach that interfaces chemical biology, nanomedicine, immunotherapy and microbiome engineering, to develop new biomedical devices for precision medicine. In particular, we utilize molecular assembly to develop peptide- and protein-based materials at both the nano- and micro-scale, that have the potential to spatially and temporally control cellular functions and augment immune responses – two important objectives towards realizing the full potential of precision medicine. Ultimately, we seek to invent novel technologies that can be rapidly translated into the clinic to improve human health. Current and on-going projects in the group include:
Ultrasound-Triggered Nano-Peptisomes for Precision Biotherapy
Proteins, peptides and nucleic acids are some of the most potent and highly-selective tools in precision medicine. In particular, biomacromolecules which can sense, track and disrupt intracellular interactions represent emerging biosensors and drug candidates, which could open unprecedented diagnostic and therapeutic opportunities, if properly delivered into cells. However, their macromolecular nature often prohibits their delivery across cell membranes to reach their intracellular target. We have recently developed a new class of self-assembled peptide nano-carrier, termed a ‘nano-peptisome’, that can be ruptured via ultrasound to deliver cell-impermeable cargo directly into target cells with high spatial resolution. We are now leveraging this technology to study biomolecular interactions of living cells in real-time, as well as developing intracellularly targeted therapies to disrupt dynamic vulnerabilities in diseased cells.
S. H. Medina*, M. S. Michie, S. E. Miller, M. J. Schnermann, J. P. Schneider*. Fluorous Phase-Directed Peptide Assembly Affords Nano-Peptisomes Capable of Ultrasound-Triggered Cellular Delivery. Angewandte Chemie Int. Ed. 2017, 56(38): 11404-11408.
Peptide-Polysaccharide Antimicrobials for Treatment of Drug-Resistant Bacterial Infections
Emergence of multidrug resistant bacteria threatens to erase many of the gains antibiotics have made in modern medicine. Pathogens responsible for human infections, particularly of the respiratory tract (e.g. pneumonia, tuberculosis), are highly adept at acquiring drug resistance mechanisms. Further, widespread and injudicious use of antibiotics by healthcare providers has accelerated selection and dissemination of resistant pathogens. To combat the growing threat of multidrug resistant superinfections requires developing new antimicrobial tools with unique mechanisms of action. Our group has recently developed a new class of biohybrid peptide-polysaccharide particles that can selectively lyse bacteria to potently kill drug-resistant pathogens with minimal side effects.
Combinatorial Biomaterials that Modulate the Human Microbiome
Bacteria play central roles in both maintaining human health, as well as causing disease. It is now clear that the beneficial microorganisms which symbiotically colonize our body, collectively known as the ‘microbiome’, are critical to homeostasis at the cell, organ and system levels. Biomaterials that can influence these microbial communities represents a new therapeutic strategy to address bacterial dysbiosis (the imbalance of ‘good’ vs. ‘bad’ bacteria) and resultant pathogenesis. Towards this goal, we are developing bio-inspired functional materials, spanning the nano-, micro- and macro-scales, that selectively interact with commensal flora in the human oral, pulmonary and gastrointesinal tracts to engineer the local microbiome and re-establish tissue homeostasis during diseased states.