Dr. Alexandra Shedlovsky, or as we knew her in McArdle, Alex Dove, moved from the study of light transmission in photoreceptors to mouse genetics in 1975. She, Bill, and their three children began this transition by a sabbatical year in Paris with Francois Jacob, one half of the pair of Jacob and Monod, famous for their analyses of the Lac Operon. Jacob had moved from bacterial to mouse genetics and Alex and Bill made a parallel change. On returning from Paris, Alex joined McArdle in 1977. Bill and his group had worked on the phage, Lambda, and on the slime mold, Physarum polycephalum, analyzing their regulation and life-cycles genetically. Moving to work with mice genetically was a major intellectual and organizational feat.
Researchers in McArdle including Betty and Jim Miller and Roz Boutwell had worked with large colonies of mice to unravel the mechanisms of chemical carcinogenesis. But their studies did not focus on genetic analyses requiring controlled matings and exact typing of offspring. Alex took charge of the demanding organization making mouse genetics feasible in McArdle. She refined the use of germline mutagenesis proving it was both powerful and practical by uncovering phenotypes that have been subsequently studied by multiple groups in multiple Universities. Alex used ENU to mutagenize mice, assayed liver extracts for the enzyme, phenylalanine hydroxylase, and identified animals deficient in this activity. These animals are informative models for the inherited human disorder, phenylketonuria (PKU). It is inherited as an autosomal recessive trait, that is, each parent has to contribute a mutated gene to their child. PKU, if untreated, can lead to damaging effects on the child’s cognitive development. Alex’s murine model has been a fundamental tool with which to understand the mechanisms underlying this disease.
Alex’s fostering mouse genetics in McArdle allowed her and the students with whom she worked to conduct successful analyses of the developmental locus, brachyury or T, which controls development of the mesoderm and for years had presented a baffling problem for developmental biologists. This same expertise was the basis for Bill’s group’s discovery of the Min locus encoding the APC gene, pivotal to the initiation of colon cancers in us. Alex guided many current McArdlites to master working with mice genetically including Andrea Bilger, Linda Clipson, Rich Halberg, and Cheri Pasch. She also worked to ensure that this research would be conducted thoughtfully and in accordance with ever evolving guidelines by serving on our Animal Care Committee and representing us in SMPH on the Medical School Institutional Animal Care and Use Committee.
Alex Dove helped to initiate much of the mouse genetics which is now basic to our cancer research. She trained numerous colleagues in this exacting work. She enriched McArdle both scientifically and personally through her quiet guidance of many of us.
–Dr. Bill Sugden, McArdle Laboratory for Cancer Research