Structural Biology/Biochemistry Seminar
Tuesday September 17, 2013
Kasha Laboratory, Room 112
11:15 AM
“Understanding cell physiology using isotope tracers and metabolic flux analysis”

Christian-MetalloDr. Christian Metallo
UC San Diego Jacobs School of Engineering
Asst. Professor in Bioengineering
Host: Dr. Tim Logan

http://www.jacobsschool.ucsd.edu/faculty/faculty_bios/index.sfe?fmp_recid=332

 

Metabolism, system biology, mass spectrometry, flux analysis, cancer, stem cell biology

Metabolism is central to virtually all cellular functions, and cells must negotiate their surrounding microenvironment to effectively utilize their surrounding nutrients.  A detailed understanding of how metabolic pathways are regulated is necessary to control cell function (e.g., stem cell fate) and identify therapeutic targets in diseases where metabolism is deregulated, including cancer, obesity, and type 2 diabetes.  To this end we apply stable isotope tracers, mass spectrometry, and metabolic flux analysis to characterize central carbon metabolism in mammalian cells, including tumor cell lines and non-transformed cells.  We have developed unique, tracer-based methods to probe glycolysis, the pentose phosphate pathway, the tricarboxylic acid cycle, and redox metabolism.  Using these approaches we have characterized how proliferating and differentiated cells regulate flux of glucose and amino acids into mitochondria for biosynthesis.  We have also applied MFA to cancer cells with specific metabolic defects to identify enzyme targets that selectively inhibit growth.  The application of systems-level approaches to cellular models greatly improves our ability to characterize intracellular metabolic processes, providing a more mechanistic understanding of pathophysiology associated with metabolic disease.