By subjecting purified CLC-ec1 to anion transport measurements, electrophysiological recording, equilibrium ligand-binding studies and X-ray crystallography, we show that F(-) binds in the Cl(-) transport pathway with affinity similar to Cl(-) but stalls the transport cycle. The recent discovery of a new CLC clade of F(-)/H(+) antiporters, which are highly selective for F(-) over Cl(-), led us to investigate the mechanism of Cl(-)-over-F(-) selectivity by a CLC Cl(-)/H(+) antiporter, CLC-ec1.
These proteins are weakly selective among anions commonly studied, including Cl(-), Br(-), I(-), NO3(-) and SCN(-), but they seem to be very selective against F(-). They aim to translate results into information that can be used in clinical practice bridging laboratory research and clinical research through multidisciplinary collaboration and methodologies.Cl(-)/H(+) antiporters of the CLC superfamily transport anions across biological membranes in varied physiological contexts. The methods they develop are used to investigate perturbations in metabolic pathways caused by disease and toxicological exposure.
The Lynch lab has developed numerous liquid-chromatography tandem mass spectrometry (LC-MS/MS), liquid-chromatography quadrupole time-of-flight (LC-QTOF) mass spectrometry, and label-free immunoassay methods for the detection and quantitation of small molecules and proteins in biological specimens. They are involved in translational research studies aimed at the clinical evaluation of novel biomarkers or biomarker panels to diagnosis, treat and monitor disease. Her research laboratory primarily focuses on identifying and quantifying endogenous and exogenous compounds in biological specimens using novel diagnostic technologies, such as mass spectrometry and biolayer interferometry, and correlating the findings with clinical pathologies. She is also the Director of Chemistry at UCSF Children's Hospital Oakland. Lynch is the Co-Director of the Core Clinical Laboratory at San Francisco General Hospital overseeing Chemistry and Toxicology.
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