Andreas Hochwagen joins Whitehead
Fellows program
CAMBRIDGE, Mass. (May 15, 2006) — Cell division
is a tricky process, one that’s driven by some
pretty 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 installed surveillance
mechanisms that guard against this. New Whitehead Fellow
Andreas
Hochwagen, who begins his Whitehead appointment
on May 15, is determined to discover exactly how our
cells guide this essential biological process.
“This is such an important aspect of basic biology,”
says Hochwagen. “Understanding the mechanisms
of cell division will provide us with tremendous insight
into other health conditions and biological functions.”
Hochwagen, who received his PhD this year from MIT,
comes to Whitehead from the laboratory of Angelika Amon,
a former Whitehead Fellow who is now an Associate Professor
of Biology at MIT and a Howard Hughes Medical Institute
Investigator. While working in her lab, Hochwagen published
a paper last fall in the journal Cell demonstrating
that a widely used drug may be meddling with meiosis,
the process by which gametes, i.e., egg and sperm cells,
are created.
With the exception of gametes, all cell’s in our
body contain two sets of chromosomes, one from our father,
one from our mother. Gametes, however, contain only
one copy of each chromosome. Only a small population
of cells in our body, called germ cells, are able, through
meiosis, to produce egg and sperm cells. This requires
many additional steps, which in turn increases the likelihood
of error.
“Meiosis requires lots of breaking up and reshuffling
of the chromosomes,” says Hochwagen. “It
can get very messy.”
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 obviously
not in the business of creating sperm and eggs, they
still undergo meiosis when they reproduce.
As Hochwagen was screening these cells to find genes
and proteins that acted as checkpoints, one item jumped
out: A key protein involved in safeguarding meiotic
cell division also is a target for rapamycin, a widely
used immunosuppressant drug given to transplant recipients.
Hochwagen then created a population of mutant yeast
cells with no ability to repair damaged DNA. “As
a result, as soon as DNA damage occurred, a strong checkpoint
response was triggered in the cells preventing any further
division,” he says.
Next, he treated those mutant cells with rapamycin,
and the result was unsettling. Within an hour of treatment,
the cells began to divide again, passing on all DNA
mistakes to the subsequent generations. Clearly, something
in rapamycin either overrode the checkpoint response,
or disabled it altogether. This suggests that patients
taking rapamycin may lack an essential component for
curbing the effects of DNA damage that occurs during
meiosis.
“This is pretty scary, because many people who
take this drug take it for life,” says Hochwagen.
“This could result in lower fertility, or in birth
defects such as Downs syndrome.”
At Whitehead, Hochwagen plans to follow up on these
results and to delve into the deeper question of how
cells repair genetic damage. “The process of repairing
broken DNA is huge,” he points out. “The
cell needs to scan the entire genome for the correct
base pairs that can fix the break. Scientists really
aren’t very clear on how this all works. With
yeast, we’re now in a position where we can address
these questions.”
“I admire Andreas’ creativity, his scientific
acumen and productivity, and his ability to find his
own way at this early juncture in his career,”
says Whitehead Director David Page.
“I’m delighted to see Andreas join the Whitehead
Fellows program,” says Angelika Amon. “His
scientific instincts are exemplary, and I have no doubt
he’ll make great contributions to the Institute.”
Whitehead Fellows are postdoctoral researchers of exceptional
promise who are given the space, resources and support
needed to start and run their own labs, without traditional
faculty responsibilities. Hochwagen, who came to the
U.S. in 2000 from Austria, will join four other current
Whitehead Fellows: Thijn Brummelkamp, Fernando Camargo,
Hui Ge, and Paul Wiggins.
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