Anchordoquy Lab
Tom Anchordoquy PhD
Professor
Department of Pharmaceutical Sciences
I joined the faculty at the CU School of Pharmacy in 1998, and my early work focused on the stability of lipid-DNA complexes during freezing, drying, and storage. In attempting to assess “recovery” of these new pharmaceutical entities, I became interested in the mechanism by which they facilitated delivery to target cells after systemic delivery. We soon recognized that the exposure of particles to serum proteins caused massive aggregation that resulted in accumulation in the lung. In an attempt to avoid the use of PEGylated components, we used high cholesterol levels to impart resistance to protein-induced perturbations. In addition to imparting stability, we documented that cholesterol forms phase-separated lipid domains within our particles that offer an optimal location for targeting ligands. Our more recent work demonstrated that these particles were being avidly taken up by circulating immune cells that elicited a potent cytokine response upon intravenous injection. After expending considerable effort attempting to evade the immune response (with little success), we have shifted our focus toward exploiting the immunogenicity of particles to limit off-target accumulation of nanomedicines and promote tumor regression. For the past decade, we have also been studying exosomes as nature’s method of delivering nucleic acids to cells. While our initial work aimed to hijack exosomes as a delivery vehicle, our current focus is on using exosomes from cow milk to enable the oral delivery of medications that typically require infusion. In addition to these projects, my lab is constantly involved in multiple formulation studies (anticancer cream, eye drops, parenterals, ointments, injectable sustained release systems) that utilize small molecules to treat a variety of conditions.
Phone:303-724-6113
Milk Exosomes. This project starts with the observation that mammalian mothers use exosomes in their milk to transfer large molecules (e.g., antibodies) from their baby’s gut into the blood. Because bovine antibodies cross-react with the human Fc receptor, cow exosomes can be used to transport therapeutic molecules from a patient’s gut to their blood. This potentially would enable a variety of molecules (chemotherapeutics, peptides, RNA) to be administered orally instead of via IV infusion. This would reduce the need for patients to travel to infusion centers and/or hospitals for treatment.
Vascular Tightening. This project exploits the fact that gene delivery vehicles elicit an antiviral response when administered systemically, i.e., the body reacts as if it is being infected. As a mechanism of limiting the spread of infection, the body signals the vasculature to limit particle uptake. However, we have observed that the immunosuppressed state of the tumor prevents this effect, thereby allowing particles to preferentially access the tumor while reducing accumulation in non-target tissues. We have recently verified that this response only are currently characterizing this phenomenon and will utilize this to improve nanoparticle-mediated delivery to tumors.
Injectable Sustained Release. This project is focused on developing a polymer-based formulation that is injected as a liquid but forms a gel under physiological conditions. The gel is composed of pharmaceutically-compatible materials that dissolve over time and are cleared from the body. By adjusting the components of the formulation, we can alter the time needed for the gel to dissolve, which ultimately determines the duration of drug release. Our current project is focused on utilizing peptides for immunotherapy to treat brain tumors, but this delivery system could potentially be optimized for other drugs.
Madison Ricco, PharmD, Graduate Student - Madison is a 2022 PharmD graduate who has been working in Dr. Anchordoquy's lab since her first year at Anschutz in 2018. While a pharmacy student, she was awarded the American Foundation of Pharmaceutical Education's 2021 Gateway to Research Award for her work on alternative dosage forms of chemotherapy. Madison has been a core member of the milk exosome project and is now a graduate student in Dr. Anchordoquy's lab working on her PhD in Pharmaceutical Sciences.
Scott Tilden, Graduate Student - Scott is a Colorado native from Golden. He graduated from the University of Colorado Boulder with a BA in Biochemistry and a BA in Molecular Cellular Developmental Biology. After graduation, Scott worked at CU Boulder for four years in the Maier/Watkins Neuroscience Laboratory and the Hough Biochemical and Biophysical Laboratory. Scott started at Anschutz in fall 2018 and joined Dr. Anchordoquy’s lab in the spring of 2019. Scott’s main interest is investigating how to induce anti-viral responses to manipulate endothelial permeability and reduce off-target toxicity/accumulation of nanomedicines. He and Dr. Anchordoquy have also working closely with a local epilepsy research company to develop novel formulation of anticonvulsant pharmaceuticals to be used in clinical trials.
| Alumnus | Current Organization |
| Dean Allison | deceased |
| Ye Zhang | Arcturus Therapeutics |
| Yvonne Lentz | Fate Therapeutics |
| Mayank Patel | Astrazeneca |
| Marion Molina | CureVac |
| Long Xu | Johnson and Johnson |
| Peter Yu | Biotech in China |
| Mayank Patel | Astrazeneca |
| Tyson Smyth | Nektar Therapeutics |
| Matt Fete | Chicago State University |
| Nicole Payton | Moderna Therapeutics |
| Max Kullberg | University of Alaska |
| Jasmina Redzic | University of Colorado |
| Scott Tilden | Student |
| Madison Ricco | Student |