Grinstaff has developed new paradigms for translating rigorous academic research into practical applications, fostering intellectual advancement, economic growth, and enhanced clinical outcomes.
During his first year at Oxy, he worked at the hummingbird section of a museum while simultaneously studying the kinetics of Friedel-Crafts chloromethylation reactions in the laboratory of Franklin DeHaan.
Gray's laboratory at the California Institute of Technology where he conducted research on electron transfer chemistry in proteins and the mechanism of alkane hydroxylation using iron porphyrins and oxygen.
The research is based on a molecular-focused approach involving the development of innovative tools and reagents, and the investigation of natural (polynucleotides, polypeptides, polysaccharides) and synthetic (polyesters, polycarbonates) polymers.
Messenger ribonucleic acid (mRNA) therapeutics are at the forefront of modern medicine as delivery of this polynucleotide results in in vivo protein production via translation.
Critical to this advance was the original discovery of the application of modified nucleosides to mRNA by Karikó and Weissman which revolutionized the field and enable clinical utility.
While saRNA shows promise in preclinical and clinical studies, it triggers a potent innate immune response which impedes its replication and protein expression and thereby restricts its therapeutic utility.
Building off the unexpected discovery that other modified nucleotides do enable successful translation in saRNA, Grinstaff, in collaboration with Dr. Wilson Wong, reported[4] significantly reduced innate immune response with substantial protein expression and duration.
An international team of scientists led by Dr. Mark Grinstaff, Dr. Orian Shirihai, and Dr. Jialiu Zeng published the first report[5] of the potential use acidic nanoparticles as a first-in-kind therapeutic for non-alcoholic fatty liver disease (NAFLD) .
In established high fat diet mouse models of NAFLD, re-acidification of lysosomes via AcNPs treatment returns liver function to lean, healthy levels with reversal of fasting hyperglycemia and hepatic steatosis.
PASs are enantiopure polypeptide-polysaccharide hybrid materials with defined molecular weights and narrow dispersities synthesized using an anionic ring-opening polymerization of a β-lactam sugar monomer.
This research led to the development of drug-eluting buttress technologies for lung tumor prevention, which have undergone clinical translation through the start-up AcuityBio, later acquired[23] by Cook Biotech Inc. Grinstaff has also explored superhydrophobic materials for biomedical applications, including drug delivery devices and diagnostic tools.
In collaboration with Dr. Yolonda Colson, flexible drug-loaded buttresses, implanted at the resection margin, prevent lung tumor and extend survival in vivo.
For instance, a rapid sensor for measuring fat content in breast milk was developed[26] to address nutritional challenges in low birth-weight infants.
Collaborative work[35] with Dr. Janne Mäkelä has expanded this area, including advancements in two-color CT imaging, which are being applied in arthritis research and therapy evaluation.
In collaboration with Dr. Yolonda Colson, Grinstaff developed[36][37][38][39] a nanoparticle-based drug delivery system with demonstrated efficacy in animal models of lung, ovarian, breast, and pancreatic cancers, as well as mesothelioma.
[47][48][49][50][51][52][53][54][55] The team also introduced[56][57][58] charge-reversal amphiphiles, which transition from cationic to anionic states to enhance DNA binding and intracellular release, improving gene delivery systems.
Crosslinkable versions of these polyester, polyamide, and polyether-ester dendritic polymers enabled the preparation of new hydrogels with targeted biodegradation, mechanical, adhesive, and swelling properties.
He developed methacrylated hyaluronic acid and alginate as macromers for photopolymerization,[72][73] complementing ongoing research by other notable scientists on photocrosslinkable polymers such as PEG by R. Langer, PLA-PEG-PLA by J. Hubbell, PVA by K. Anseth, and PPF-PEG by A. Mikos for in-situ hydrogel formation.