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Laurie Boyer’s studies of stem cell differentiation could improve treatments for heart disease.
Anne Trafton | MIT News Office
April 3, 2015
up near Springfield, Mass., Laurie Boyer was always interested in
science but didn’t have many opportunities to satisfy her curiosity. She
was unsure how to pursue a career in science and was instead encouraged
to put her energy into working after school.
However, Boyer persevered and became the first person in her family
to attend college, eventually earning a PhD and joining the faculty of
MIT’s Department of Biology, where she recently earned tenure. She now
studies how cells regulate the complex genetic pathways that control
their development from stem cells to mature tissues, especially cardiac
“I have always been inspired and motivated by solving complex
problems in biology,” says Boyer, the Irwin and Helen Sizer Career
Development Associate Professor in Biology at MIT. “I’m so incredibly
curious that it’s a driving force. I have to have the answer.”
That search for answers has led her to discoveries that may help
scientists develop new treatments for heart disease and other
conditions, by mimicking how cells naturally transition from immature to
mature states, and vice versa.
“The heart has extremely limited capacity to regenerate itself,” she
says. “Being able to understand how heart cells are generated during
development may actually provide a potential therapeutic down the road.”
Eager for knowledge
After graduating from Framingham State College in 1990, Boyer says
she knew a lot about laboratory techniques, but “I still didn’t have a
great sense of the big picture, or what the process of doing research
was all about,” she recalls.
She got a job at Boston University’s School of Medicine performing
clinical tests to diagnose prenatal genetic disorders, which piqued her
interest in the mechanisms behind such disorders. “I always had too many
questions, and I really wanted to understand the disease,” Boyer says.
“Then I worked at Integrated Genetics, which was owned by Genzyme, for a
number of years, and again I felt like I always had questions about
mechanisms, and how does this work, and why does this happen, and what’s
the biology behind it.”
Her supervisor at Integrated Genetics, who had been a postdoc in
David Housman’s lab at MIT, encouraged her to take a class that Housman
was teaching in the Harvard-MIT Division of Health Sciences and
Technology on the molecular basis of genetic disease.
“Twice a week, I would drive to Harvard early in the morning to take
the class, and then I would drive to work in Framingham and stay at work
late. I loved it,” Boyer says. “At Integrated Genetics we were
developing assays for prenatal diagnostics for diseases like spinal
muscular atrophy and cystic fibrosis, and I really wanted to understand
why these mutations caused a disease, not just test for them.”
The class made her want to apply to graduate school, but she had never had any experience working in an academic lab.
During the class semester, she mustered the courage to speak with
Housman about her dream of pursuing a research career. “Before I knew
it, he is driving me over to his lab at the time, in E17, and I started
volunteering with a postdoc of his. I would work at Genzyme during the
day, but then I couldn’t wait to get to MIT to work half the night with
this postdoc. From the first minute I was in that environment, it’s like
all the lights went on, and I found the energy and the buzz of people
discussing science so exciting,” Boyer says.
She spent about a year working in Housman’s lab, looking for genes
that might play a role in susceptibility to melanoma. Inspired by this
experience, she decided to apply to the University of Massachusetts
Medical School for graduate school, where she studied chromatin — the
complex formed by DNA and the proteins that surround it.
Working in Craig Peterson’s lab, Boyer studied chromatin remodeling
and its role in gene regulation. This was around the time, in the
mid-1990s, that scientists first began to think of chromatin as having
an important regulatory role in turning genes on and off.
After getting her PhD, Boyer joined Rudolf Jaenisch’s lab as a
postdoc at the Whitehead Institute. There, her interests shifted toward
understanding how genes are controlled during embryonic development as
stem cells differentiate in specialized tissues. Working with Jaenisch
and Richard Young, she identified gene targets for three transcription
factors known to be necessary for stem cells to remain pluripotent —
OCT4, SOX2, and NANOG.
The paper describing those results, published in Cell
in 2005, has been cited nearly 3,000 times. That paper, along with the
discovery that a type of proteins called polycomb group proteins help
control cell fate by repressing certain genes, earned Boyer and Young a
spot on Scientific American’s 2006 list of 50 top scientists and science policymakers.
What drives development
In 2007, Boyer joined the MIT faculty as a member of the Department
of Biology, where she continues to study chromatin structure as well as
genetic and epigenetic control of development. In particular, she has
begun to focus on factors that drive development of the heart.
“The heart is highly sensitive to perturbations in gene expression,”
Boyer says. “It’s really critical that genes are precisely regulated at
the temporal and spatial level. Even subtle perturbations of gene
expression programs during development can lead to congenital heart
defects, or even worse, failure to survive.”
In a recent study published in the journal Cell, Boyer’s lab
showed that in addition to transcription factors, RNA molecules that do
not code for proteins are critical players in regulating the expression
of heart genes during development. In another study published in Circulation Research,
they characterized the gene expression profiles that allow mice, during
the first week of life, to regenerate injured heart cells. “For many
years it was thought that mammals did not have this capacity,” Boyer
says. “It turns out they do, but they lose it once heart muscle cells
fully mature during this one-week window in mice.”
Boyer’s work suggests that heart cells have an intrinsic ability to
reverse their developmental clock back to an immature state, which
allows them to divide and produce more heart tissue, just like embryonic
heart cells. “If we can understand this process at the molecular level,
perhaps we can identify factors that we can exploit to promote
regeneration,” Boyer says.