All cellular biology stories

Drug based on MGH discovery may significantly improve treatment of dangerous blood disorder

yvette — Mon, 04 Feb 2008 15:51:43 -0500

Two clinical trials of the novel drug romiplostim (Nplate) show that it significantly improved platelet levels in patients with chronic immune thrombocytopenic purpura (ITP), a hematologic disorder that can cause uncontrolled bleeding. An international research team reports Phase 3 trial results for the drug, which duplicates the action of a natural hormone discovered by a Massachusetts General Hospital (MGH) investigator, in the February 2 issue of The Lancet.

Stem cells may enhance capability of heart cells to regenerate

jake — Mon, 22 Oct 2007 12:21:50 -0400

During a fatal heart attack, at least 1 billion heart cells are killed in the left ventricle, one of the heart’s two big lower pumping chambers that move blood into the body.

In less severe coronaries, dead cardiac cells are replaced by connective tissue cells that form scar tissue in the damaged heart. But the result is never very satisfactory. Scarred ventricular walls are thin, and don’t contract very well — a problem in a workhorse organ designed for sustained pumping.

Inadequate heart repair concerns British-trained developmental biologist Christine Mummery, who has made cardiac cells her specialty. She’s the Harvard Stem Cell Institute Radcliffe Fellow, and will be in residence at Harvard for a semester.

Biohybrid of elastic film and muscle cells packs a punch

50443248 — Mon, 01 Oct 2007 16:04:05 -0400

In an innovative marriage of living cells and a synthetic substrate, bioengineers at Harvard University have found that a rubberlike, elastic film coated with a single layer of cardiac muscle cells can semi-autonomously engage in lifelike gripping, pumping, walking, and swimming. The tissue engineering feat was reported in the Sept. 7 issue of the journal Science.

The researchers, led by Kevin Kit Parker and Adam W. Feinberg, report that the exact movement undertaken by these hybrid muscular thin films (MTFs) can be tailored by controlling muscle alignment relative to the shape of the flexible film. Some of the MTFs even contract spontaneously, an intrinsic property of cardiac muscle that allows the devices to move around without user intervention.

Brain implants relieve Alzheimer’s damage

50443248 — Mon, 01 Oct 2007 15:53:35 -0400

Genetically engineered cells implanted in mice have cleared away toxic plaques associated with Alzheimer’s disease.

The animals were sickened with a human gene that caused them to develop, at an accelerated rate, the disease that robs millions of elderly people of their memories. After receiving the doctored cells, the brain-muddling plaques melted away. If this works in humans, old age could be a much happier time of life.

Alzheimer’s involves a protein called amyloid-beta, which makes up gooey clots or plaques that form in the brain. These toxic clumps, along with accessory tangled fibers, kill brain cells and interfere with memory and thinking. The situation has been compared to a build-up of cholesterol in coronary arteries.

Major progress toward cell reprogramming

Tue, 10 Jul 2007 09:34:31 -0400

Two Harvard Stem Cell Institute (HSCI) researchers and scientists at Whitehead Institute and Japan's Kyoto University have independently taken major steps toward discovering ways to reprogram cells in order to direct their development - a key goal in developmental biology and regenerative medicine.

Additionally, the group led by Kevin Eggan, an HSCI principal faculty member - whose study is featured on the cover of the latest issue of the journal Nature - has disproved a long-held view of developmental biologists by demonstrating in mice that it is possible to use previously fertilized ova to produce disease-specific stem cell lines using somatic cell nuclear transfer (SCNT) - commonly referred to as therapeutic cloning.

Manipulating genetic switch in mice eases MD symptoms

Tue, 10 Jul 2007 15:57:40 -0400

Scientists at Dana-Farber Cancer Institute have shown in a laboratory study that revving up a crucial set of muscle genes counteracts the damage caused by a form of muscular dystrophy.

Reporting in the April 1 issue of Genes and Development, the researchers demonstrated that manipulating a genetic molecular switch increased the genes’ activity in the muscles of mice with Duchenne muscular dystrophy, slowing the disease-associated muscle wasting. The authors caution that they have not yet found a way to tweak the switch, known as PGC-1alpha, in humans.

Study questions 'cancer stem cell' hypothesis in breast cancer growth

Wed, 11 Jul 2007 09:27:17 -0400

A Dana-Farber Cancer Institute study challenges the hypothesis that "cancer stem cells" — a small number of self-renewing cells within a tumor — are responsible for breast cancer progression and recurrence, and that wiping out these cells alone could cure the disease.

Instead, the scientists report in the March issue of Cancer Cell that they have identified two genetically distinct populations of cancer cells in samples of human breast tumors — one of the types being a cell recently proposed by other scientists to be a true breast cancer stem cell.

Practical way to target cancer cell mutations demonstrated

Wed, 11 Jul 2007 11:53:45 -0400

A study led by researchers at Dana-Farber Cancer Institute and Broad Institute of the Massachusetts Institute of Technology and Harvard University provides the first demonstration of a practical method of screening tumors for cancer-related gene abnormalities that might be treated with "targeted" drugs.

The findings, published online Feb. 11 on the Nature Genetics Web site, may help relieve a bottleneck between scientists' expanding knowledge of the genetic mutations associated with cancer and the still-nascent ability of doctors to use that knowledge to benefit patients. The results constitute an important step toward the era of "personalized medicine," in which cancer therapy will be guided by the particular set of genetic mutations within each patient's tumor, the authors suggest.

"It's universally recognized that cancer is a disease of the genome, of mutations within genes responsible for cell growth and survival, and a great deal of effort has gone into finding those mutations, to the point where several hundred to a thousand are now known," said the study's senior author, Levi Garraway, of Dana-Farber and the Broad Institute. "The challenge has been how to determine which of them are involved in each of the hundreds of kinds of cancer that occur in humans - and to develop accurate, affordable methods of detecting key mutations in tumor samples. This study suggests that such a method is feasible on a large scale."

The authors took advantage of a scientific serendipity to devise a simple test to detect important cancer mutations. Mutations in oncogenes (genes linked to cancer) do not occur randomly; rather, they seem to arise most frequently in certain regions of the oncogenes. As a result, researchers didn't necessarily have to scan the entire length of each gene, but could focus instead on the sections most likely to harbor mutations.

Major funding for the study was provided by grants from Genentech, Inc. the American Cancer Society, the National Cancer Institute, the Prostate Cancer Foundation, the Burroughs-Wellcome Fund, the Robert Wood Johnson Foundation, and the Novartis Institute for Biomedical Research.

Mystery muscles make mightier mice

Wed, 11 Jul 2007 13:31:36 -0400

Scientists have muscled in on a genetic switch that allows mice to run longer and faster. Humans possess the same switch, so the discovery might open new paths to treating muscle-wasting diseases and building better bodies.

Last year, Bruce Spiegelman and Alfred Goldberg, professors of cell biology at Harvard Medical School, found that a gene called PGC-1 alpha protects skeletal muscles from wasting away. Spiegelman had discovered alpha in 1998 and a sister gene he named PGC-1 beta in 2002. After finding that alpha has such intriguing prospects, he began experiments to see if beta might also be used to treat such diseases as muscular dystrophy, Lou Gerhrig's disease, and various forms of paralysis.

Research finds mutation that causes Noonan syndrome

Wed, 11 Jul 2007 15:36:31 -0400

Scientists have discovered that mutations in a gene known as SOS1 account for many cases of Noonan syndrome (NS), a common childhood genetic disorder that occurs in one in 1,000 to 2,500 live births. NS is characterized by short stature, facial abnormalities, and learning disabilities, as well as heart problems and predisposition to leukemia.

Led by researchers at Harvard Medical School-Partners Healthcare Center for Genetics and Genomics (HPCGG) and Beth Israel Deaconess Medical Center (BIDMC), the findings are reported in the December issue of Nature Genetics, which appeared online Dec. 4.

"Noonan syndrome is the most common single-gene cause of congenital heart disease," explains co-senior author Benjamin Neel, director of the Division of Cancer Biology at BIDMC and a professor of medicine at Harvard Medical School (HMS).

"Although previous work had identified mutations in the PTPN11 gene as the cause of Noonan syndrome in nearly 50 percent of cases [and mutations in an oncogene known as KRAS in a small subset of severe cases], the identity of the gene or genes responsible for fully half the cases had not been elucidated," Neel said.

To identify candidate genes, a group led by HMS instructor Amy Roberts and HPCGG's scientific director Raju Kucherlapati conducted genetic analysis of more than 100 children with Noonan syndrome. This large cohort of NS patients had neither PTPN11 nor KRAS mutations.

This work was supported, in part, by grants from the National Institutes of Health and the National Center for Research Resources.

Key antibody IgG links cells' capture and disposal of germs

Thu, 12 Jul 2007 09:35:21 -0400

Scientists have found a new task managed by the antibody that's the workhorse of the human immune system: Inside cells, immunoglobulin G (IgG) helps bring together the phagosomes that corral invading pathogens and the potent lysosomes that eventually kill off the germs.

The research, by Axel Nohturfft at Harvard University and colleagues at Harvard, Massachusetts General Hospital, and the Massachusetts Institute of Technology (MIT), appears this week in the Proceedings of the National Academy of Sciences (PNAS).

Cells that work themselves to death

Thu, 12 Jul 2007 09:57:33 -0400

When you're fighting flu or any other infection, your body mobilizes battalions of cells to defend against the invading viruses or bacteria. But once the invaders have been defeated and you've recovered from aches, fever, headaches, and a sore throat, your body has to get rid of the now-unneeded fighting cells. If left alone, they can attack healthy tissues.

One way to muster them out is signaling them to commit suicide. Sounds cruel, but it's a natural protective process called "apoptosis." It is the same strategy that the human immune system uses to get rid of tumor cells.

Important signal uncovered in brain development

Thu, 12 Jul 2007 10:51:55 -0400

Nobody has counted them, but the best estimates put the number of human brain cells in the trillions. The best known among them, called neurons, do the heavy thinking and remembering. Each of these cells can connect to 10 or more others, forming a vast network of feelings, thoughts, memories, prejudices, and PINS.

But neurons don't do their jobs alone. They are supported and regulated by an immense system of star cells, called astrocytes, because of their shape. New research has discovered how these stars are born. The discovery also hints at how defective astrocytes may contribute to Alzheimer's disease.

It has been known for years that both neurons and astrocytes come from the same brain stem cells. But how do these cells know whether and when to make one or the other?

Study shows different insulin signaling components control glucose and lipid metabolism in the liver

70652986 — Mon, 26 Mar 2007 06:27:20 -0400

Insulin uses two distinct mechanisms to control glucose and the metabolism of blood fats (lipids) in the liver, a new Joslin Diabetes Center-led study has discovered. Failures in each of these networks can lead to serious health problems: the breakdown of glucose metabolism that can lead to type 2 diabetes, and the malfunction of lipid metabolism contributing to metabolic syndrome, which is a cluster of conditions that puts people at increased risk of heart disease, vascular disease and type 2 diabetes.

The new study, led by C. Ronald Kahn, M.D., and Cullen Taniguchi, M.D., Ph.D., of Joslin Diabetes Center in Boston and their colleagues, is published in the May 2006 edition of Cell Metabolism. The findings open the door to the development of new treatments that one day may target directly the conditions that contribute to type 2 diabetes and the metabolic syndrome. "Patients with the metabolic syndrome have high levels of both glucose and lipids in the blood. We now understand that insulin that controls the pathways that control glucose levels are different from those that regulate lipid levels. By targeting these specific pathways, we might be able to improve problems with glucose metabolism, lipid metabolism or both," says Kahn, president of Joslin Diabetes Center and Mary K. Iacocca Professor of Medicine at Harvard Medical School.

Proteasome recognized as nuclear player on gene-transcription team

70652986 — Mon, 26 Mar 2007 06:26:37 -0400

One of the most common agents in the cytoplasm of the cell, the proteasome, also plays a widespread and critical role in transcription from inside the cell nucleus.

Pam Silver, Kathryn Auld, and their colleagues report in the March 17, 2006 Molecular Cell that the proteasome binds and critically regulates the transcription of some of the most highly expressed and important genes in the yeast genome, including those involved in lipid metabolism, mating behavior, and the making of ribosomal proteins.

"We found the proteasome to be very important in so many roles in yeast transcription that I cannot imagine it is not important in other organisms," Auld said.