The Rosania lab studies the microscopic transport properties of small drug-like molecules inside cells. Our overarching hypothesis is that a drug's microscopic distribution within organelles is as important as its macroscopic distribution in organs in determining efficacy and toxicity. We use microscopic imaging instruments to capture the local distribution and dynamics of small molecules inside cells and analyze image data with innovative computational tools and statistical strategies, combining cheminformatics and machine vision to relate the chemical structure of small molecules to their subcellular distribution. We also develop biochemical analysis methods to study the microdistribution and cellular pharmacokinetics of small drug-like molecules. Lastly, we build mathematical models to simulate drug transport and distribution in single cells and higher order cellular organizations, based on biophysical principles governing molecular transport phenomena at the cellular level.
We envision a day when drugs are designed, optimized, and approved based on their site of action, much as drugs today are designed, optimized, and approved based on their molecular mechanism of action.
Exploring the application of in silico models, such as the cell-based molecular transport simulations we use in our experiments, to pharmaceutical discovery and development
Exploring cell-based molecular transport simulations as a way to probe the role of microscopic drug transport as a determinant of drug absorption, distribution, metabolism, and excretion
Using mathematical and experimental approaches to explore how specific chemical moieties can be used to massively target small-molecule drugs to specific cell types in animals and humans
Dissemination of free modeling and simulation tools to help educate the next generation of pharmaceutical scientists and medicinal chemists and to facilitate the development of drugs neglected by the pharmaceutical industry
- 2018 American Association of Pharmaceutical Scientists Fellow, AAPS
- 2007 Presidential Early Career Award for Scientists and Engineers, US Government
- 2004 Exterior Colombia Award for Excellence in the USA, Colombia Exterior
Rzeczycki P, Woldemichael T, Willmer A, Murashov MD, Baik J, Keswani R, Yoon GS, Stringer KA, Rodriguez-Hornedo N, Rosania GR.(2018) An Expandable Mechanopharmaceutical Device (1): Measuring the Cargo Capacity of Macrophages in a Living Organism.Pharmaceutical Research. 2018; 36(1):12
Rzeczycki P, Yoon GS, Keswani RK, Sud S, Baik J, Murashov MD, Bergin IL, Stringer KA, Rosania GR. (2018) An Expandable Mechanopharmaceutical Device (2): Drug Induced Granulomas Maximize the Cargo Sequestering Capacity of Macrophages in the Liver. Pharmaceutical Research. 2018; 36(1):3.
LaLone V, Mourão MA, Standiford TJ, Raghavendran K, Shedden K, Stringer KA, Rosania GR. (2018) An Expandable Mechanopharmaceutical Device (3): a Versatile Raman Spectral Cytometry Approach to Study the Drug Cargo Capacity of Individual Macrophages. Pharmaceutical research 36(1):2.
Woldemichael T, Keswani RK, Rzeczycki PM, Murashov MD, LaLone V, Gregorka B, Swanson JA, Stringer KA, Rosania GR. (2018) Reverse Engineering the Intracellular Self-Assembly of a Functional Mechanopharmaceutical Device. Sci Rep. Feb 13;8(1):2934. doi: 10.1038/s41598-018-21271-7.