Tag: Sabatini Lab

Electron microscope image of a mitochondrion

Amino acid shortage curbs proliferation in cells with mitochondrial dysfunction

July 31, 2015

According to Whitehead Institute researchers, cells with malfunctioning mitochondria are unable to proliferate due to a shortage of the amino acid aspartate, not because of an energy crisis, as was once thought. Mitochondrial dysfunction plays a role in a host of relatively rare disorders as well as neurodegenerative disorders, including Parkinson’s disease.

Image of brain samples showing gene activity in ischemic areas

Biologists identify brain tumor weakness

April 8, 2015

Biologists at Whitehead Institute and MIT have discovered a vulnerability of brain cancer cells that could be exploited to develop more-effective drugs against brain tumors.

Dividing human mammary stem cells

Age discrimination during cell division maintains the ‘stem’ in stem cells

April 2, 2015

A team of Whitehead Institute scientists has discovered that during division, stem cells distinguish between old and young mitochondria and allocate them disproportionately between daughter cells.

Transmembrane protein SLC38A9 appears to act as a nutrients sensor for the mTORC1 metabolic pathway

Scientists identify first nutrient sensor in key growth-regulating metabolic pathway

January 7, 2015

Scientists in the lab of Whitehead Institute Member David Sabatini have for the first time identified a protein that appears to be a nutrient sensor for the key growth-regulating mTORC1 metabolic pathway. 

Diagram of the Sestrins' role in mTORC1 regulation

New protein players found in key disease-related metabolic pathway

September 25, 2014

Cells rely on the mechanistic target of rapamycin complex 1 (mTORC1) pathway—which senses the availability of nutrients—to coordinate their growth with existing environmental conditions. The lab of Whitehead Member David Sabatini has identified a family of proteins that negatively regulate the branch upstream of mTORC1 that senses amino acids, the building blocks of proteins.

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.

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