Jaenisch Lab

A widely conserved family of RNA-binding proteins known to be expressed in neural stem cells and other stem cell types has now been shown to play a role in controlling both the state and behavior of breast cancer cells.

Induced neural stem cells (iNSCs) hold promise for therapeutic transplantation, but their potential in this capacity has been limited by failed efforts to maintain such cells in their multi-potent NSC state. Now, Whitehead Institute scientists have created iNSCs that remain in the multi-potent state—without ongoing expression of reprogramming factors. This allows the iNSCs to self-renew repeatedly to generate cells in quantities sufficient for therapy.

Induced pluripotent stem cells (iPSCs) may hold the potential to cure damaged nerves, regrow limbs and organs, and perfectly model a patient’s particular disease. Yet these cells can acquire serious genetic and epigenetic abnormalities that lower the cells’ quality and limit their therapeutic usefulness. Now Whitehead Institute researchers have identified a cocktail of reprogramming factors that produces very high quality iPSCs.

Embryonic stem cell (ESC) research has been hampered by the inability to transfer research and tools from mouse ESC studies to their human counterparts, in part because human ESCs are “primed” and slightly less plastic than the mouse cells. Now researchers in the lab of Whitehead Institute Founding Member Rudolf Jaenisch have discovered how to manipulate and maintain human ESCs into a “naïve” or base pluripotent state similar to that of mouse ESCs without the use of any reprogramming factors.

Whitehead Institute researchers have identified a potential dual-pronged approach to treating Niemann-Pick type C (NPC) disease, a rare but devastating genetic disorder. By studying nerve and liver cells grown from NPC patient-derived induced pluripotent stem cells (iPSCs), the scientists determined that although cholesterol does accumulate abnormally in the cells of NPC patients, a more significant problem may be defective autophagy—a basic cellular function that degrades and recycles unneeded or faulty molecules, components, or organelles in a cell. Here, the scientists propose two drugs, one to reduce cholesterol buildup and the other to induce autophagy, as a strategy for treating NPC.

The German Society for Biochemistry and Molecular Biology (GBM) will present this year’s Otto Warburg Medal to Whitehead Institute Founding Member Rudolf Jaenisch later this month.

Whitehead Institute researchers have determined that the lipid storage disorder Niemann-Pick type C1 (NPC1) disease is caused not only by defects in cholesterol processing but also in autophagy—a key cellular degradation pathway that malfunctions in many neurodegenerative diseases.

A team of researchers from Whitehead Institute and Sanford-Burnham Research Institute has brought new clarity to the picture of how gene-environmental interactions can kill nerve cells that make dopamine. The study uses patient-derived stem cells to show that a mutation in the α-synuclein gene causes increased vulnerability to pesticides, leading to Parkinson’s disease.

Whitehead Institute researchers have discovered that the protein product of the gene MECP2, which is mutated in about 95% of Rett syndrome patients, is a global activator of neuronal gene expression. Mutations in the protein can cause decreased gene transcription, reduced protein synthesis, and severe defects in the AKT/mTOR signaling pathway.

A new study from a team of Whitehead and MIT researchers reveals a gene that is critical to the process of memory extinction. Enhancing the activity of this gene, known as Tet1, might benefit people with posttraumatic stress disorder (PTSD) by making it easier to replace fearful memories with more positive associations.