Research Interests

Drug resistance is a major problem in treating a variety of diseases including fungal infections and cancer.  Members of my lab are working to better understand how cells become resistant to a variety of drugs, including anticancer ruthenium complexes.

Metal-based drugs have long been used in cancer chemotherapy, because these compounds readily damage the DNA of rapidly dividing cells, ultimately causing these cells to die.  Ruthenium-based compounds have the added advantage that with different ligands, the oxidation state of ruthenium can be fine-tuned so that these complexes selectively target hypoxic cells like those found in solid tumors.  In collaboration with Dr. Laura Stultz, students synthesize various ruthenium complexes and subsequently test the ability of these drugs to kill rapidly growing yeast cells, which serve as a model for cancer.  Students also study genetic alterations that result in resistance to these ruthenium-based drugs.

Multidrug resistance is a particularly challenging phenomenon that impairs clinical treatment of bacterial and fungal infections, as well as cancer.  Resistance to drugs with diverse targets and structures can arise through a variety of mechanisms, including global changes in gene expression, upregulation of "promiscuous" drug pumps that can act on a wide range of substrates, and alteration of the membrane bilayer, which can reduce passive diffusion of lipophilic drugs into the cell.  Currently, we are focused on the role of sphingolipid metabolism in regulating transporter trafficking as well as bilayer permeability.



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