Mark Jeffrey, D.Phil

Mark Jeffrey
Mark Jeffrey, D.Phil

Mark Jeffrey, D.Phil, develops mathematical analytical models that offer greater insights into magnetic resonance spectroscopy (MRS) and mass spectrometry studies of the flux through metabolic pathways. Such metabolic biochemical pathways constitute the machinery by which the cell breaks down energy-containing molecules to extract energy to power the cell, and also builds molecules needed for cell structure and function. Dr. Jeffrey's models have been applied to studies of metabolism of the heart, liver, and brain.

In his research, Dr. Jeffrey is developing analytical models that can extract more information from MRS, as well as mass spectrometry, studies in which researchers use tracer molecules synthesized to contain more than one atom of the 13C isotope. In MRS, this heavier, non-radioactive carbon isotope is widely used as a tracer to enhance MRS signals from natural components of metabolic pathways, enabling researchers to follow the fate of compounds in those pathways.

When a tracer molecule contains one 13C, it produces a single peak, or singlet, in the MRS spectrum. However, a tracer molecule with two such carbon atoms produces a "doublet" that reflects the interaction between the two atoms. Or, doublets in the spectrum will also be produced when two singly labeled molecules combine in the biochemical pathways, creating a doubly labeled molecule. Dr. Jeffrey's analytical models enable interpretation of the biochemical significance of such doublets in MRS spectra, offering researchers more detailed understanding of the progress of reactions in metabolic pathways.

Researchers can also gain deeper insight into the functioning of metabolic pathways by administering molecules with different patterns of 13C isotope labeling and using Dr. Jeffrey's analytical models to compare the MR spectra to distinguish the flux through different components of the complex, multi-branched pathways.

Dr. Jeffrey's models have enabled neurologists to distinguish the metabolic pathways of two different types of cells in the brain—glial cells and neurons. Glial cells support and protect neurons, which are the brain cells that transmit nerve impulses in the brain. Better understanding of the distinctive metabolism of these two types of cells is aiding fundamental understanding of brain function.

He is also collaborating with researchers in the AIRC's Mouse Metabolic Phenotyping Center to characterize the metabolic abnormalities in the hearts of mice with genetic heart defects. Specifically, he and his colleagues are analyzing the relationships between utilization of fatty acids and glucose as energy sources in the hearts of the mutant mice.

In other studies, Dr. Jeffrey is collaborating with neurologist Juan Pascual to analyze the metabolic defects in patients with Glut1 deficiency, a genetic defect that causes impaired entry of glucose, the cell's chief energy source, into the brain from the bloodstream. Better understanding of metabolism in this disorder could lead to treatments in which patients receive alternative energy-containing molecules, enabling them to lead more normal lives.

For publication information please view Dr. Jeffrey's faculty profile.