Ruth Lehmann Elected as Director of Whitehead InstituteWhitehead Institute for Biomedical Research
Lehmann, a world renowned developmental and cell biology researcher, as the Institute’s fifth Director
Lehmann, a world renowned developmental and cell biology researcher, as the Institute’s fifth Director
A team of scientists has uncovered a surprising molecular link connecting how cells regulate growth with how they sense and make available nutrients. The findings also implicate a new protein as a potential drug target in pancreatic cancer.
For the first time, scientists have directly linked deletions in two genes in zebrafish and traits, such as seizures, hyperactivity, large head size, and increased fat content. Both genes are in a genome region linked to autism spectrum disorder, developmental delays, seizures, and obesity in humans
For more than a century, the link between thyroid hormone and red blood cell production has remained elusive. Now, Whitehead scientists have teased about the mechanism that connects them, which could help scientists identify new therapies for specific types of anemia.
Whitehead Institute Member David Sabatini will be this year’s recipient of the Dickson Prize in Medicine. The annual award is the University of Pittsburgh School of Medicine’s highest honor and recognizes “an American biomedical researcher who has made significant, progressive contributions to medicine”.
The transition from an egg to a developing embryo is one of life’s most remarkable transformations. Now Whitehead Institute researchers have used fruit flies to decipher how one aspect—control of the translation of messenger RNAs (mRNAs) into proteins—shifts as the egg becomes an the embryo. This type of switch could tell scientists more about how human cells work and embryos develop.
Many cultures traditionally use herbs believed to increase milk supply – so called galactagogues – although scientific data are lacking. Now Whitehead Institute Member Jing-Ke Weng and the Family Larsson-Rosenquist Foundation are teaming up to explore the effects of galactagogues on milk production.
Whitehead Institute scientists have identified a gene that could help clinicians discern which patients have aggressive forms of early stage breast cancer, which could prevent hundreds of thousands of women from undergoing unnecessary treatment and save millions of dollars.
Using red blood cells modified to carry disease-specific antigens, scientists from Whitehead Institute and Boston Children’s Hospital have prevented and alleviated two autoimmune diseases—multiple sclerosis (MS) and type 1 diabetes—in early stage mouse models.
Researchers at Whitehead Institute have now uncovered a role for the protein-folding chaperone HSP90 in humans, not only as a modifier of the effects of mutations, but as a mediator of the impact of the environment on the function of mutant proteins. And these effects of HSP90 can alter the course of human diseases.
Parkinson’s disease (PD) and other “synucleinopathies” are known to be linked to the misfolding of alpha-synuclein protein in neurons. Less clear is how this misfolding relates to the growing number of genes implicated in PD through analysis of human genetics. Researchers affiliated with Whitehead Institute and Massachusetts Institute of Technology (MIT) explain how they used a suite of novel biological and computational methods to shed light on the question.
Whitehead Institute researchers provide insight into a specific gene pathway that appears to regulate the growth, structure, and organization of the human cortex. They also demonstrate that 3D human cerebral organoids can be effective in modeling the molecular, cellular, and anatomical processes of human brain development.
The use of proteasome inhibitors to treat cancer has been greatly limited by the ability of cancer cells to develop resistance to these drugs. But Whitehead Institute researchers have found a mechanism underlying this resistance—a mechanism that naturally occurs in many diverse cancer types and that may expose vulnerabilities to drugs that spur the natural cell-death process.
Targeting human genes required for HIV infection but not T cell survival may avoid inducing treatment resistance
The Susan Lindquist Chair for Women in Science will advance the work of women who are leaders in biomedical research and role models for emerging female scientists. It honors a singular scientist who blazed a path—for women and men alike—into new realms of discovery.
Whitehead Institute researchers have determined how the master transcriptional regulator of the heat shock response, known as heat shock factor 1 (HSF1), is controlled in yeast. Understanding how HSF1 works, how it is regulated, and how to fine tune it in a cell-type specific way could lead to therapies for cancer and neurodegenerative diseases.
Researchers using a mouse model of Rett Syndrome find that cortical pyramidal neurons have faults in excitatory and inhibitory signaling; and demonstrate why recombinant human Insulin Like Growth Factor 1 has had therapeutic effects for RTT patients in clinical trials.
“Sue has meant so much to Whitehead as an institution of science, and as a community of scientists, and her passing leaves us diminished in so many ways,” reflects David C. Page, M.D., Director of Whitehead Institute
Using an unbiased screen in yeast, a team of Whitehead Institute and Stanford University scientists have identified dozens of prion-like proteins that could change the defining characteristics of these unusual proteins.
Inherited methylation—a form of epigenetic regulation passed down from parents to offspring—is far more dynamic than previously thought and may contribute to changes in the brain and other tissues over time. This finding by Whitehead Institute scientists challenges current understandings of gene regulation via methylation, from development through adulthood.
Whitehead Institute researchers have conducted the first genome-wide screen in Apicomplexa, a phylum of single-celled parasites that cause diseases such as malaria and toxoplasmosis. The screen sheds light into the vast, unstudied reaches of parasite genomes, uncovering for instance a protein common to all apicomplexans.
Whitehead Institute scientists have developed a method to quickly isolate mitochondria from mammalian cells and systematically measure the concentrations of mitochondrial metabolites. Mitochondrial dysfunction is found in several disorders, including Parkinson’s disease, cardiovascular disease, and mitochondrial diseases. Until now, peering into the inner metabolic workings of these vital organelles has been very challenging.
Whitehead Institute scientists have identified a potential antifungal mechanism that could enable combination therapy with fluconazole, one of today’s most commonly prescribed fungal infection treatments. Severe, invasive fungal infections have a mortality rate of 30-50% and cause an estimated 1.5 million deaths worldwide annually.
Whitehead Institute scientists have created a checklist that defines the “naive” state of cultured human embryonic stem cells (ESCs). Such cells provide a better model of early human embryogenesis than conventional ESCs in later stages of development.
Using tiny, alpaca-derived, single-domain antibody fragments, Whitehead Institute scientists have developed a method to perturb cellular processes in mammalian cells, allowing them to tease apart the roles that individual proteins play in these pathways. With improved knowledge of protein activity, scientists can better understand not only basic biology but also how disease corrupts cellular function and identify potential therapeutics to rectify these aberrations.
Using a novel method, Whitehead Institute researchers have determined how mutations that are not located within genes are identified through genome-wide association studies (GWAS) and can contribute to sporadic Parkinson’s disease, the most common form of the condition. The approach could be used to analyze GWAS results for other sporadic diseases with genetic causes, such as multiple sclerosis, diabetes, and cancer.
In a finding with enormous implications for cancer diagnostics and therapeutics, Whitehead Institute scientists have discovered that breaches in looping chromosomal structures known as “insulated neighborhoods” can activate oncogenes capable of fueling aggressive tumor growth.
Over the past decade, studies have found that obesity and eating a high-fat, high-calorie diet are significant risk factors for many types of cancer. Now, a new study from Whitehead Institute and MIT’s Koch Institute for Integrative Cancer Research reveals how a high-fat diet makes the cells of the intestinal lining more likely to become cancerous.
Whitehead Institute researchers have created a hydrogel scaffold that replicates the environment found within the human breast. The scaffold supports the growth of human mammary tissue from patient-derived cells and can be used to study normal breast development as well as breast cancer initiation and progression.
The germinal centers that form in the body’s lymph nodes work as a fitness boot camp in which B cells evolve to produce antibodies of increasingly higher affinity to an invading pathogen. This new finding from Whitehead Institute scientists overturns a previously held notion that only a narrow range of B cells can survive this training and go on to secrete high-affinity antibodies. This revised understanding may aid development of effective vaccines against HIV, influenza, and other viruses that mutate rapidly.
Whitehead Institute researchers have created a new mouse-human modeling system that could be used to study neural crest development as well as the modeling of a variety of neural crest related diseases, including such cancers as melanoma and neurofibromatosis. Mouse-human chimeras would fill an important gap in disease research, as existing models do not accurately mimic key disease processes, including solid tumor initiation and progression, and are of little value for studying diseases with long latencies, such as Alzheimer’s and Parkinson’s.
Whitehead Institute researchers have created a map of the DNA loops that comprise the three dimensional (3D) structure of the human genome and contribute to gene regulation in human embryonic stem cells. The location of genes and regulatory elements within this chromosomal framework will help scientists better navigate their genomic research, establishing relationships between mutations and disease development.
Whitehead Institute researchers have determined the organization of a protein complex that is critical during chromosome segregation. Without the foundation it supplies, the link between chromosome and kinetochore would fail, as would chromosome segregation and cell division.
Scientists at Whitehead Institute and Broad Institute of MIT and Harvard have for the first time identified the universe of genes in the human genome essential for the survival and proliferation of human cell lines or cultured human cells.Their findings and the materials they developed in conducting the research will not only serve as invaluable resources for the global research community but should also have application in the discovery of drug-targetable genetic vulnerabilities in a variety of human cancers.
Whitehead Institute scientists have at last answered the long-standing question of how the growth-regulating pathway known as mechanistic target of rapamycin complex 1 (mTORC1) detects the presence of the amino acid leucine—itself a key player in modulating muscle growth, appetite, and insulin secretion.
Whitehead Institute researchers have developed a tool that allows scientists to monitor changes in DNA methylation over time in individual cells. Certain diseases, including cancer, cause changes in DNA methylation patterns, and the ability to document these alterations could aid in the development of novel therapies.
A protein known to play a role in transporting the molecular contents of normal cells into and out of various intracellular compartments can also turn such cells cancerous by stimulating a key growth-control pathway.
In the breast, cancer stem cells and normal stem cells can arise from different cell types and tap into distinct yet related stem cell programs, according to Whitehead Institute researchers. The differences between these stem cell programs may be significant enough to be exploited by future therapeutics.
Upsetting the balance between protein synthesis, misfolding, and degradation drives cancer and neurodegeneration. Recent cancer treatments take advantage of this knowledge with a class of drugs that block protein degradation, known as proteasome inhibitors. Widespread resistance to these drugs limits their success, but Whitehead researchers have discovered a potential Achilles heel in resistance. With such understandings researchers may be able to target malignancy broadly, and more effectively.
By teasing apart the structure of an enzyme vital to the parasites that cause toxoplasmosis and malaria, Whitehead Institute scientists have identified a potentially ‘drugable’ target that could prevent parasites from entering and exiting host cells.
Leveraging a novel system designed to examine the double-strand DNA breaks that occur as a consequence of gene amplification during DNA replication, Whitehead Institute scientists are bringing new clarity to the causes of such genomic damage. Moreover, because errors arising during DNA replication and gene amplification result in chromosomal abnormalities often found in malignant cells, these new findings may bolster our understandings of certain drivers of cancer progression.
Diamond Blackfan anemia (DBA), a rare inherited bone marrow failure syndrome is typically treated with glucocorticoids that cause a host of often dangerous side effects. Using a mouse model, Whitehead scientists have determined that combining the drug fenofibrate with glucocorticoids could allow for dramatically lower steroid doses in the treatment of DBA and other erythropoietin-resistant anemias. These promising results are the foundation for a clinical trial that will begin soon.
A novel approach that allows real-time imaging of the immune system’s response to the presence of tumors—without the need for blood draws or invasive biopsies—offers a potential breakthrough both in diagnostics and in the ability to monitor efficacy of cancer therapies.
Candida albicans causes potentially lethal infections in immunocompromised individuals. Now, using a modified CRISPR-Cas system, Whitehead researchers can edit the fungus’s genome systematically—an approach that could help identify potential drug targets.
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.
Whitehead Institute scientists have for the first time identified a protein that appears to be a nutrient sensor for the key growth-regulating mTORC1 metabolic pathway.
Long known for its ability to help organisms successfully adapt to environmentally stressful conditions, the highly conserved molecular chaperone heat-shock protein 90 (HSP90) also enables estrogen receptor-positive (ER+) breast cancers to develop resistance to hormonal therapy.
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.
An exhaustive effort to sequence the mouse Y chromosome reveals a surprisingly large and complex biological beast, at the same time providing remarkable insight into a heated battle for supremacy between mammalian sex chromosomes.
A team of Whitehead Institute scientists has discovered the surprising manner in which an enigmatic protein known as SUUR acts to control gene copy number during DNA replication. It’s a finding that could shed new light on the formation of fragile genomic regions associated with chromosomal abnormalities.