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Bio
I began my career interested in mechanisms of genetic recombination and chose to use yeast as a model system since I could combine genetic and molecular biological tools that were rapidly being developed in the ‘70s and ‘80s. Early on we showed that plasmids containing double-strand DNA breaks were repaired using homologous genomic sequences, which lead directly to genetic engineering, gene disruption and later to the double-strand break repair model. Using the tools that we developed, I next turned my attention to both study and search for genes involved in genome stability. We examined many of the central genes involved in genetic recombination (RAD52, RAD51, RAD1, RAD10 etc.) and also discovered new key players in this process, including TOP3, SGS1, the Shu complex and IRC genes. Since DNA repair is essential for preserving genome integrity in all organisms, it is not surprising that most of these genes are evolutionarily conserved. Several years ago, using fluorescently tagged proteins, we developed yeast strains that allow us to follow events from the initiation of the damage to its repair. These strains allow us to study the movement of chromosomes and to determine their spatiotemporal relationships during the DNA damage response, uncovering the inherent choreography of this process. The lab is also interested in using the power of yeast genetic screens to identify new connections between cellular pathways. By overexpressing a protein from one pathway, we look for genetic interactions with mutations in another pathway that cause a “synthetic” effect using colony growth as a metric. As an example, we have found new connections in the secretory pathway in a collaboration with Elizabeth Miller and Randy Schekman. We are also using yeast as a model to study cancer and cancer predisposition. We are especially interested in gene overexpression, an underexploited area of cancer biology. We find that almost all of the pathways identified in our yeast screens are conserved in mammalian cells. We have on-going collaborations with many members of my department as well as the Cancer Center, including Alberto Ciccia, Chao Lu, Zhiguo Zhang, Dawn Hershman and Gary Schwartz to exploit our yeast findings in mammalian cells. During this COVID-19 pandemic, we have turned our attention to using our yeast expertise to explore the way SARS-CoV-2 viral proteins affect host pathways. We have at our disposal humanized yeast strains containing human proteins with which viral proteins interact. We have outstanding colleagues, including Vincent Racaniello and Amy Rosenfeld, with whom I am collaborating on this project. Finally, I am committed to the training and mentoring of students and post-docs. For the past 35 years at Columbia University Medical Center, I have trained 22 PhD students including 3 URMs (with 2 more PhD students in progress, one of whom is a URM) and 22 post-docs, many of whom are professors at various stages in their careers. Some are involved in the biotechnology industry, patent law or science filmmaking. More than 30 undergraduates have passed through my lab on their way to graduate or medical school.
Research Interests
Papers共 202 篇Author StatisticsCo-AuthorSimilar Experts
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Michael T Kimble, Aakanksha Sane, Robert Jd Reid, Matthew J Johnson,Rodney Rothstein,Lorraine S Symington
bioRxiv : the preprint server for biology (2024)
Genes & developmentno. 7-8 (2024): 354-354
bioRxiv (2022)
Genome Medicineno. 1 (2021): 1-3
CELLSno. 6 (2021): 1433
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