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We are searching for biosignatures that could indicate whether life exists on other planets. In particular, we are pursuing the hypothesis that some lipids may be uniquely generated by living systems and could be reliable indicators of life on other planets. To test this idea, we are collecting samples from lava tube environments on earth that are similar to lava tubes on Mars, which we think are particularly suitable to harbor life. We are evaluating the types of lipids found in these lava tube samples, and whether they can serve as reliable biosignatures.
In our Cancer Biology projects, we seek to understand how different types of cancer cells and immune cells control tumor survival, and what therapeutic strategies can be used to target various cancers. We are exploring the role of ferroptosis in several cancers, such as brain and liver cancers, examining the mechanism of drug resistance, and using single-cell methods to characterize the heterogeneity and the microenvironment in solid tumors.
We use diverse chemical and biological tools to elucidate new mechanisms related to cell death, metabolism, and disease. For example, we design small molecule inhibitors and activators of proteins using high resolution structural information and computational chemistry tools. We also create imaging probes to determine where different biomolecules are located in cells and tissues.
We are designing small molecules that can be used as pan-viral inhibitors for preventing the pandemics of the future.
Ferroptosis is a form of cell death driven by iron-dependent oxidation of specific lipids that and was first reported in the Stockwell Lab in 2012. Our ongoing research in ferroptosis seeks to define how cells die during ferroptosis, key regulators of ferroptosis, and how ferroptosis can be harnessed for therapeutic benefit through pharmacological and dietary interventions.
We use mass spectrometry imaging to determine the profile of lipids and metabolites present through tissues and different cell types, in normal and disease tissues, and in response to genetic and pharmacological modulation. For example, we have performed desorption ionization (DESI) mass spectrometry imaging of mouse and human liver, as shown in the image below.
We examine the role of kinases and of ferroptosis in a variety of neurodegenerative diseases, including Huntington Disease and ALS. We design, synthesize, and evaluate novel small-molecules as probes and potential therapeutics, then test them in cell and animal models of these diseases.