all Todd Golub stories

Genetic 'road map' leads to discoveries

Thu, 12 Jul 2007 10:55:58 -0400

A research team led by scientists at the Broad Institute of MIT and Harvard announced Sept. 28 the development of a new kind of genetic "road map" that can connect human diseases with potential drugs to treat them, as well as predict how new drugs work in human cells. Called the "connectivity map," the new tool and its uses are described in the Sept. 29 issue of Science and in separate publications in the Sept. 28 immediate early edition of Cancer Cell. The three papers show the map's ability to accurately predict the molecular actions of novel therapeutic compounds and to suggest ways that existing drugs can be newly applied to treat diseases such as cancer.

Gene chips aid drug search in rare cancers

70652986 — Mon, 26 Mar 2007 06:26:04 -0400

When Kimberly Stegmaier was a pediatric oncology fellow at Dana-Farber and Children's Hospital Boston six years ago, she says,"I was struck by how poorly our young patients with AML (acute myeloid leukemia) do." Long-term survival is about 50 percent, compared with 80 percent from those with the more prevalent ALL (acute lymphoblastic leukemia).

Clearly, better drugs could save lives, but AML is relatively rare and not a likely priority for pharmaceutical companies. Moreover, scientists haven't identified a specific molecular defect common to all AML cells that could be corrected with an existing or "designer" drug. If such a target were known, it would simplify testing a large number of possible drugs (a process known as "screening") to identify compounds that cause a desired change in the target.

At the time, the young pediatric oncologist was a member of the laboratory of Todd Golub of Dana-Farber and the Broad Institute in Cambridge. Golub, among other things, has pioneered the use of gene chips - or microarrays - to classify different types of cancer on the basis of their distinctive genetic activity patterns, or gene expression "profiles."

AML cells, which proliferate uncontrollably and take over the normal bone marrow, are in a state of arrested development. They are immature, dividing abnormally, and unable to become specialized blood cells. Unfortunately, the abnormal proteins or molecular pathways responsible for failed maturation are poorly understood.

Stegmaier and Golub came up with a new approach for screening. First, they'd capture the gene expression profile, or signature, of an immature AML cell and that of a mature, normal blood cell, and identify genes that were expressed differently between them. The next step was to expose the cells in the laboratory to thousands of drugs and chemicals, observing which of the compounds changed the cancerous gene signature to a normal one. Those chemicals merited further testing as potential AML treatments.

After screening more than 1,700 chemicals, the scientists got 13 novel "hits" - compounds that altered the gene profiles of the cancerous cells, and of those, eight reliably induced the gene signature of mature cells. One of the compounds is already being tested in a Phase II clinical trial at Dana-Farber for AML, says Stegmaier.

A new way to identify cancers is found

50443248 — Tue, 24 Jul 2007 09:39:41 -0400

Scientists are surprised and delighted that a recently discovered group of small molecules show an unexpected potential for easily distinguishing healthy cells from tumors and one type of cancer from others. These molecules, known as microRNAs (miRNAs), provide fingerprints that may enable doctors to quickly and inexpensively diagnose any type of cancer.
When miRNAs are present in insufficient numbers, it is believed that cells may divide without proper regulation, a hallmark of cancer. In other words, miRNAs may play a role in keeping cells on a normal growth track.

Researchers find better way to predict childhood brain tumor outcomes

70652986 — Mon, 26 Mar 2007 05:19:12 -0400

About 2,000 children a year are diagnosed with medulloblastoma, or brain tumor. In a study, researchers examined gene expression patterns from 99 patient tumor samples of three different types of brain tumors. In addition to distinguishing tumor types from each other, the study found strong expression of a signaling protein known as "Sonic Hedgehog," which is supposed to be turned off after it performs its crucial functions during fetal brain developing. Pediatric neurologist Scott Pomeroy, associate professor at Harvard Medical School, was first author of the study, which confirmed other work in fruit flies and humans implicating mutations in the Hedgehog signaling pathway as responsible for turning normal cerebellum into cancerous cells. "The bottom line [of the study] is that there exists a gene expression signature of outcome in childhood medulloblastoma, and this signature is detectable at the time of diagnosis, before patients receive treatment," says pediatric oncologist Todd Golub, senior author of the study paper. "It is important not only for medulloblastoma, but because it suggests that such signatures are likely to be detectable for other cancers as well." Golub is an assistant professor of pediatrics at Harvard Medical School and holds joint appointments at several Boston hospitals.

Diagnosis by database shows promise

70652986 — Mon, 26 Mar 2007 05:16:55 -0400

A relatively new approach to researching cancer involves looking at the actions of thousands of genes in cancer tumors. This technique just recently became possible because, using new applications of technology, researchers are able to make "diagnoses by database." At Harvard Medical School, several teams of researchers have recently discovered new types of cancer or new ways to diagnose known cancers by analyzing what are called the "gene expression patterns" of thousands of genes in diseased cells. The researchers involved in this work include postdoc Arindam Bhattacharjee in the Dana-Farber lab of pathologist Matthew Meyerson, Harvard Medical School (HMS) assistant professor of pathology; pediatric oncologist Scott Armstrong in the Dana-Farber laboratory of Stanley Korsmeyer; Dana- Farber oncologist Margaret Shipp, an HMS associate professor; Children's Hospital pediatric neurologist Scott Pomeroy, an HMS associate professor of neurology; Dana- Farber oncologist Sridhar Ramaswamy, an HMS instructor; Todd Golub, HMS assistant professor of pediatrics; and Eric Lander, director of the genome center at the Whitehead Institute of Biomedical Research and Massachusetts Institute of Technology.

Scientists using gene chips identify unique form of leukemia

70652986 — Mon, 26 Mar 2007 05:18:24 -0400

Currently, physicians diagnose and treat a rare form of cancer that strikes infants as a particularly aggressive form of the more common acute lymphoblastic leukemia. The cancer may respond to chemotherapy at first, but it tends to recur fatally. That's why the prognosis is so much worse than for most types of childhood leukemia, which today can usually be treated effectively. Using the relatively new technology of gene chips, scientists working at Dana-Farber Cancer Institute have discovered that this rare leukemia is genetically distinct from other types of leukemia.