Monessha Nambiar, Ph.D.

Project 1: Peptide and lipid conjugates for the tunable release of small molecule inhibitors, proteins and probes - Designed and synthesized hydrolytically stable warhead suitable for reversible tethering of cysteine-containing probes and proteins to peptide amphiphiles. - Developed a library of lipid-drug conjugates for incorporation into liposomal formulations, that enabled therapeutic release at defined rates though controlled linker hydrolysis. - Performed structure-activity relationship (SAR) studies to optimize biological activity and therapeutic performance of peptide and lipid-based conjugates. Project 2: Immune-responsive peptide hydrogels for precise regulation of allotransplantation rejection - Synthesized a library of enzyme-cleavable peptide hydrogels to achieve spatiotemporal delivery of JAK inhibitors. - Conducted extensive biophysical characterization of peptides to study temperature-dependent beta sheet folding and assessed shear-thinning properties of hydrogels through oscillatory rheology. - Fostered a cross-institutional collaboration toward preclinical assessment of the efficacy of peptide hydrogels in murine hind-limb transplant models and achieved prolonged transplant survival. Project 3: Liver-specific CAR-T cell optimization assisted by targeted nucleic acid delivery via lipid nanoparticles - Formulated mRNA-LNPs that enable desired chemokine display on the surface of hepatocellular carcinoma cells to achieve optimal CAR-T cell targeting of the liver. - Conducted routine quality control assessments of LNPs, ascertaining physicochemical properties such as encapsulation efficiency, surface charge, size and polydispersity.

Thesis Project: Exploring Higher-Order Alpha-Helical Peptide Assemblies for Biomaterial Applications - Synthesized a library of ligand-modified coiled-coil peptides and established design principles for their hierarchical assembly. - Assessed alpha-helical secondary/tertiary folding and characterized metal-mediated peptide assemblies via electron microscopy. - Investigated the assembled nanostructures for in vitro delivery of chemotherapeutics as well as determined toxicity/uptake in different cell lines. • Independently supervised a team of 15 graduate teaching assistants wherein I managed laboratory instruction including lab safety, maintained adherence to standard operating procedures (SOPs), developed manuals and supervised assessment and grading of laboratory skills. • Mentored undergraduate students (freshman-senior year levels) undertaking maiden research projects by inducting them into safe laboratory practices and imparting the research skills required to build a strong foundation for early career research scientists. Notable Conference Presentations: • 5th Annual Notre Dame-Purdue Symposium on Soft Matter and Polymers: Metal-mediated assembly of alpha-helical peptide bundles into microspheres. South Bend, IN (October 2018) • BASF Research Forum (Invited): Self-assembly of coiled-coil peptides into nanostructured drug-delivery vehicles. Iselin, New Jersey (August 2018) • 35th Annual H.C. Brown Lectures: Reversible hierarchical assembly of trimeric coiled-coil peptides into banded nano- and micro- structures. West Lafayette, IN (April 2018) • 25th American Peptide Symposium: Higher-order assembly of coiled-coil trimers into banded microstructures. Whistler, BC, Canada (June 2017)

Research Project: Study of the applications of structural and chemical modified nanoporous membranes in protein separation involving the use of porous alumina as the base substrate, modified with materials like titania, gold and silanes to create and produce membranes capable of highly selective molecular separations. Selected Conference Presentations • International Conference on Nanoscience and Nanotechnology (ICONN): Study of titania modified porous alumina membranes for protein transport and separation. Perth, Australia (February 2012) • CHEMECA: Fabrication of titania nanotube membranes by atomic layer deposition using naoporous alumina as a template. Sydney, Australia (September 2011)

Research Theme: Investigation of the use of glycolipid coated carbon nanotubes in drug delivery systems using single walled carbon nanotubes modified with glycolipids to examine their affinity towards target proteins.

Research Advisor: Prof. Jean Chmielewski

Honors Project Thesis - “Carbon nanotube array-based sensor for metal ion detection” Research Theme: Design and fabrication of an electrochemical biosensor using a vertical array of single walled carbon nanotubes with peptide-modified ends for sensing target metal ions in aqueous environments.