Andreas Hochwagen

Fellow, Whitehead Institute 617.324.1716 phone andi@wi.mit.edu

Cell division is a tricky process, one that’s driven by some heavy back-end calculus. If anything goes wrong in the equation, the resulting daughter cells can be plagued by genetic mistakes that lead to birth defects or cancer. Fortunately, our cells have built-in surveillance mechanisms that guard against this. Whitehead Fellow Andreas Hochwagen is determined to discover exactly how our cells oversee this essential biological process.

With the exception of egg and sperm cells, all cells in our bodies contain two sets of chromosomes, one from our fathers and one from our mothers. Egg and sperm cells, however, contain only one copy of each chromosome. Only a small population of cells in our bodies, called germ cells, can produce egg and sperm cells, through the process known as meiosis. This process requires many additional steps, which in turn increase the likelihood of error.

Luckily, our cells constantly monitor the integrity of DNA. If mistakes are found, the cells repair these mistakes prior to further division. These mechanisms are called checkpoints.

Early in Hochwagen’s graduate work, he decided that yeast would be the perfect testbed for understanding how these checkpoints work. While yeast cells are not in the business of creating sperm and eggs, they still undergo meiosis when they reproduce.

Hochwagen discovered that a widely used immunosuppressant drug called rapamycin may be interfering with a cell’s ability to correct genetic mistakes during meiosis, a finding that’s particularly alarming since patients who take this drug often take it for life.

At Whitehead, Hochwagen continues to delve into the deeper question of how cells repair genetic damage, something for which yeast continues to provide us with essential insights. In 2007, the Hochwagen lab used yeast to develop a new method that precisely locates the sites of meiotic chromosome break formation. These breaks are normally tightly controlled and are needed for chromosome transmission. The resulting break profiles from Hochwagen’s work provided fundamental new insights into the transmission of small chromosomes and showed that the ends of chromosomes serve as key regulators of this process.

Hochwagen received his PhD in 2006 from MIT, in the lab of former Whitehead Fellow and Howard Hughes Medical Institute Investigator Angelika Amon. In 2006 he received a Smith Family Award for Excellence in Biomedical Research, in 2001 the Diploma Thesis Award from the Austrian Chemical Society, and in 2000 the Boehringer Ingelheim Fund Doctoral Fellowship Award.

Selected publications

Blitzblau H.G., Bell G.W., Rodriguez J., Bell S.P., Hochwagen A. (2007). Mapping of meiotic single-stranded DNA reveals double-stranded-break hotspots near centromeres and telomeres. Curr Biology Dec 4;17(23):2003-12.

Hochwagen A., Amon A. (2006). Checking Your Breaks: Surveillance Mechanisms of Meiotic Recombination. Curr Biology 16 (6), R217-28.

Hochwagen A., Tham W.-H., Brar G.A., Amon A. (2005). The FK506-binding protein Fpr3 counteracts protein phosphatase 1 to maintain meiotic recombination checkpoint activity. Cell 122 (6): 861-73.

Hochwagen A., Wrobel G., Cartron M., Demougin P., Niederhauser-Wiederkehr C., Boselli M., Primig M., Amon A. (2005). A novel response to microtubule perturbation in meiosis. Mol Cell Biol, 25 (11): 4767-81.

Haering C.H., Lowe J., Hochwagen A., Nasmyth K. (2002). Molecular architecture of SMC proteins and the yeast cohesin complex. Mol Cell, 9 (4): 773-88.

Panizza S., Tanaka T., Hochwagen A., Eisenhaber F., Nasmyth K. (2000). Pds5 Cooperates with Cohesin in Maintaining Sister Chromatid Cohesion. Curr Biology,10 (24): 1557-64.

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