Tag: Sabatini Lab

Schematic of how interrupting ATPIF1 rescues cells with mitochondrial dysfunction

Scientists find potential target for treating mitochondrial disorders

March 27, 2014

Mitochondria, long known as “cellular power plants” for their generation of the key energy source adenosine triphosphate (ATP), are essential for proper cellular functions. Mitochondrial defects are often observed in a variety of diseases, including cancer, Alzheimer’s disease, and Parkinson’s disease, and are the hallmarks of a number of untreatable genetic mitochondrial disorders whose manifestations range from muscle weakness to organ failure. Whitehead Institute scientists have identified a protein whose inhibition could hold the key to alleviating suffering caused by such disorders.

Diagram of the Nutrostat machine

How diabetes drugs may work against cancer

March 16, 2014

Scientists at Whitehead Institute have pinpointed a major mitochondrial pathway that imbues cancer cells with the ability to survive in low-glucose environments. By identifying cancer cells with defects in this pathway or with impaired glucose utilization, the scientists can predict which tumors will be sensitive to these anti-diabetic drugs known to inhibit this pathway.

Image of scissors cutting DNA

New gene-editing system enables large-scale studies of gene function

December 12, 2013

Since the completion of the Human Genome Project, which identified nearly 20,000 protein-coding genes, scientists have been trying to decipher the roles of those genes. A new approach developed at MIT, the Broad Institute, and the Whitehead Institute should speed up the process by allowing researchers to study the entire genome at once.

Image showing how cells with and without normal FLCN gene react to nutrients

Gene responsible for hereditary cancer syndrome found to disrupt critical growth-regulating pathway

November 7, 2013

Whitehead Institute scientists report that the gene mutated in the rare hereditary disorder known as Birt-Hogg-Dubé cancer syndrome prevents activation of mTORC1, a critical nutrient-sensing and growth-regulating cellular pathway.   

Image of GATOR1's location in cells where it is functional and nonfunctional

Protein complex in key cell-growth pathway could help predict response to cancer therapy

May 30, 2013

Whitehead Institute researchers have identified a protein complex that, when mutated, sends the master growth regulatory pathway known as mTORC1 into overdrive. Researchers believe that mutations in this complex could serve as biomarkers to predict response to rapamycin treatment in cancer patients.

Image of autophage markers in cells with and without RagA activated

Nutrient-sensing enzymes key to starvation response and survival in newborn mammals

December 23, 2012

One enzyme, RagA, has been found to regulate the mechanistic target of rapamycin complex 1 (mTORC1) pathway in cells according to glucose and amino acid availability. When this regulation breaks down in fasting newborn mice, the animals suffer a nutritional crisis and die.

Graphical explanation of MCT1's role in 3-BrPA's uptake by some cancer cells

Cell surface transporters exploited for cancer drug delivery

December 2, 2012

According to Whitehead Institute researchers, a protein known as monocarboxylate transporter 1 (MCT1), which is highly expressed in a subset of metabolically altered cancer cells, is needed for the entry of the investigational cancer drug 3-bromopyruvate (3-BrPA) into malignant cells.

Image:  Computer-generated model of mTORC1

On the path to age-defying therapies

March 29, 2012

By teasing apart rapamycin’s activity at the cellular level, researchers at Whitehead Institute and the University of Pennsylvania have determined that inhibiting only the protein cluster known as the mechanistic target of rapamycin complex 1 (mTORC1) prolongs life in mice without adversely affecting glucose tolerance or insulin sensitivity.

Key metabolic pathway implicated in intractable form of breast cancer

July 18, 2011

Using a new in vivo screening system, Whitehead Institute researchers have identified a protein in a key metabolic pathway that is essential in estrogen receptor (ER)-negative breast cancer.

Scientists discover new component of key growth-regulating signaling pathway

June 10, 2011

Researchers in the lab of Whitehead Institute Member David Sabatini have identified a previously unknown substrate of the mammalian target of rapamycin (mTOR) kinase, called Grb10. Linking Grb10 activity to mTOR provides a more detailed understanding of the function of mTOR and may open up new areas for mTOR research.

Leucine deprivation proves deadly to malignant melanoma cells

May 16, 2011

Whitehead Institute researchers have found that depriving human melanoma cells of the amino acid leucine can be lethal to the cells, suggesting a possible strategy for therapeutic intervention. The researchers observed the effect in melanoma cells with a mutation in the RAS/MEK signaling pathway—the most common mutation found in the deadliest form of skin cancer.

Mammalian aging process linked to overactive cellular pathway

December 22, 2010

Whitehead Institute researchers have linked hyperactivity in the mechanistic target of rapamycin complex 1 (mTORC1) cellular pathway to reduced ketone production in the liver, which is a well-defined physiological trait of aging in mice.

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