Joanne Keene Kelleher
Collaborator
Email: jkk (at) mit (dot) edu
Joanne Keene Kelleher grew up in Kentucky where she developed a strong interest in biomedical research. She had the great fortune to be mentored as a student by Helmut Gordon, Professor of Pharmacology at the University of Kentucky.
She studied chemistry at St. Louis University (B.S. 1969) and Biological Sciences at Boston University (PhD 1976) where her PhD advisor was Lynn Margulis. In the Margulis she was exposed to the intense narrow-minded thinking of prominent molecular and evolutionary biologists of the day who dismissed the endosymbiotic origin of eucaryotic cells. Fortunately, protein and DNA sequencing arrived a few years later to reveal the importance of endosymbiosis as an evolutionary mechanism that created eucaryotic cells.
While in graduate school she saw great opportunity to advance biomedical research using computers to model biochemical and physiological processes. As a postdoctoral student she worked with Barbara E. Wright at Harvard who pioneered computer models of cellular enzymatic pathways to predict developmental outcomes. Unleashing the power of the digital computer to models biochemical pathways was exciting but frustrating as the cost of computer time limited the number of hypotheses that could be tested.
In 1978 she was appointed as Assistant Professor of Physiology at George Washington University Medical School in Washington DC. At GW she established a laboratory in Metabolic Physiology. An important goal of the laboratory was to develop and test computer aided mathematical models of metabolic pathways. The requirement to test a model against experimental data led to a strong focus on isotopic tracer methodology. Key methodologies developed by the laboratory included a radioisotope method, “Acetate CO2 Ratios” which probed the anaplerotic functions of the TCA cycle. Moving to stable isotopes a key methodology was “Isotopomer Spectral Analysis” a nonlinear regression method to quantified polymer biosynthesis. This approach and was especially useful for de novo lipogenesis and the ability to estimate reductive carboxylation as a pathway from glutamine to lipids.
Since 2000 she has been affiliated with the Metabolic Engineering group directed by Professor Gregory Stephanopoulos in the Chemical Engineering Department at MIT. At MIT, a major goal to further the applications engineering methodologies to human metabolic research and human nutrition.