Breast cancer survivor offers wisdom at Faulkner satellite center
Call 877-422-3324 today to make an appointment
Make your appointment or second opinion with Dana-Farber today to meet with an onsite specialist.
Can’t get to Boston? Explore our Online Second Opinion service to get expert advice from Dana-Farber oncologists.
Toll-Free Number866-408-DFCI (3324)
Discover the ways to give and how to get involved to support Dana-Farber.
Poet Richard Fox gains insight – and material – through cancer treatment
A family faces cancer in an unfamiliar city – with help
Choosing mastectomy or not: Studying young women's surgical choices
Jeff's targeted therapy has kept his advanced lung cancer at bay.
A decade ago, Dana-Farber pediatric oncologist and researcher Todd Golub, MD, pioneered the use of DNA microarrays to
classify cancers based on their gene expression signatures, a
technique used worldwide today. Recently, with colleague Kimberly Stegmaier, MD, a former postdoc in his lab, Golub
finessed this technique into an unconventional drug discovery tool.
Known as gene expression-based high-throughput screening (GE-HTS),
this approach makes ingenious use of genomics to identify
anti-tumor compounds even when their molecular targets are unknown
or considered un-druggable.
In GE-HTS, investigators first define the gene expression
signature of a desired biological state, such as differentiation,
and then screen a library of small molecules for compounds that
induce this target signature and corresponding phenotype.
In collaboration with the Broad Institute, where Golub is
director of the cancer program, Stegmaier and colleagues
demonstrated the feasibility of GE-HTS in a landmark study of acute
myeloid leukemia (AML), a cancer in which white blood cells fail to
After comparing gene expression profiles of undifferentiated AML
cells with their mature myeloid counterparts, the investigators
selected a core signature of five genes that collectively acted as
a surrogate for the differentiation phenotype. "The tricky part,"
says Stegmaier, "was figuring out how to quantify the expression of
this collection of genes affordably in 384 wells," the format of
small-molecule libraries. Of the technologies available at the
time, Stegmaier and Golub chose mass spectrometry, building on an
assay used by Levi Garraway, MD, PhD, to measure mRNA levels after cells were
exposed to 1,700 small molecules provided by the Broad. This work
led to identification of candidate compounds that reliably
reproduced the target signature. Based upon the results of this
screen, Dana-Farber investigators are now collaborating with
industry partners to test a new drug for patients with AML.
With recent enhancements to bead-based Luminex technology,
investigators gain the capacity to analyze expression of up to 500
genes simultaneously, increasing both the sensitivity and
specificity of screening and enabling the study of increasingly
intricate gene expression patterns induced by small molecules, says
Stegmaier, of the Department of Pediatric Oncology. "This opens up
new possibilities in predicting synergy between compounds,
screening for very complex biological signatures, and analyzing
multiple phenotypes in a single screen."
Search by last name:
Browse directory of