Mary Jo Ondrechen (born 1953) is an American chemist, educator, researcher, community leader and activist. She serves as Professor of Chemistry and Chemical Biology and Principal Investigator of the Computational Biology Research Group at Northeastern University in Boston, Massachusetts. Ondrechen received an American Chemical Society certified bachelor's degree in chemistry from Reed College, Portland, Oregon, in 1974. She pursued doctoral studies in Chemistry and Chemical Physics at Northwestern University, Evanston, Illinois, and earned the Ph.D. degree in 1978, under the direction of Mark A. Ratner. After postdoctoral research appointments at the University of Chicago and at Tel-Aviv University in Israel, the latter as a NATO Postdoctoral Fellow, she joined the faculty at Northeastern University in Boston, Massachusetts in 1980. Her earlier research achievements include the design of molecules and materials with desirable spectroscopic and conductive properties, prediction of electric field effects in molecules and proteins, the optimization of energy conversion devices, and the design and characterization of ionic conductor materials for rechargeable batteries. Her current research activities include modeling of biological macromolecules and predictive calculations for functional genomics. She co-developed THEMATICS (Theoretical Microscopic Anomalous Titration Curve Shapes), a simple computational predictor of functional information about proteins from their three-dimensional structure alone. THEMATICS predicts catalytic and binding sites in proteins with high sensitivity and good selectivity. A unique and powerful feature of her THEMATICS method is that it requires neither sequence nor structural comparisons and hence applies to novel folds, orphan sequences, and also to engineered polypeptide systems. She is also the co-developer, with Wenxu Tong and Ronald J. Williams, of a novel machine learning technology called Partial Order Optimum Likelihood (POOL).