all Immune Disease Institute stories

Discovery of calcium channel protein illuminates T cell signaling

70652986 — Mon, 26 Mar 2007 06:26:42 -0400

A rare genetic defect in a family has helped researchers identify a key signaling component in T cells.

The newly identified protein, Orai1, may be a piece of a long- sought calcium channel in T cells that is critical for lymphocyte function. When two siblings inherited two copies of a mutant form of Orai1, it caused a severe impairment of their immune systems.

Now, more than a decade after their case was reported, Yousang Gwack and Stefan Feske in Anjana Rao's lab have found the protein responsible for the disease. Their findings appear in the April 2, 2006 Nature.

RNA sequence restrains fatal encephalitis

70652986 — Mon, 26 Mar 2007 06:25:17 -0400

One short sequence of RNA protected mice from deadly brain inflammation caused by West Nile virus and Japanese encephalitis virus, report Priti Kumar, Manjunath Swamy, and Premlata Shankar. The findings, which appear online and in the April 2006 PLoS Medicine, underscore the therapeutic potential of the fast-moving field of RNA interference. It has only been four years since scientists first showed that RNA interference, which protects plants, flies, and worms from viral infections, also works in mammalian cells. Now, at least two experimental siRNA therapies already have advanced to phase I safety trials in people. Short interfering RNA (siRNA) silences genes most commonly by triggering the destruction of RNA before proteins can be made.

Innate signal sparks homing of T cells

70652986 — Mon, 26 Mar 2007 05:32:03 -0400

The results of three studies published together in the Aug. 31, 2003 online edition of Nature Immunology help explain the uncanny ability of T cells to home to problem areas in the body and suggest potential new mechanisms to treat inflammatory diseases, such as asthma. When one fast-acting lipid hits the panic button about a wound, invading pathogen, or asthma-triggering antigen, it not only calls in the short-acting attack cells of the innate immune system for immediate battle, it also recruits the first T cells, the better-armed troops of the adaptive immune system that can escalate and sustain the conflict. The similar findings come from different investigative trails taken by researchers in the labs of Andrew Luster, Harvard Medical School (HMS) associate professor of medicine at Massachusetts General Hospital; Ulrich von Andrian, HMS associate professor of pathology at the CBR Institute for Biomedical Research; and a third group at the National Jewish Medical and Research Center in Denver.

Resistance mutation found for Gleevec

70652986 — Mon, 26 Mar 2007 05:24:18 -0400

The drug Gleevec was stunningly successful in treating patients with chronic myelogenous leukemia (CML) at early stages of disease, but quickly stopped working in most patients with more advanced forms of CML. Last year, researchers at UCLA headed by Charles Sawyers found that some resistant patients carried a mutant version of Bcr-Abl. The original mutation, T315I, confers resistance by altering the enzyme's physical structure to block Gleevec from binding. Now, in what appears to be a serendipitous twist, Harvard Medical School researchers have discovered what is responsible for the inability of some patients with CML to respond to Gleevec (formerly STI-571). They have found a version of the rogue enzyme, Bcr-Abl, that resists Gleevec's arrows. "We weren't looking for Gleevec-resistant mutants," said Richard Van Etten, Harvard Medical School associate professor of genetics at the Center for Blood Research. Van Etten along with Sergei Roumiantsev, Bradley Brasher, and colleagues reported the discovery in the Aug. 6, 2002, Proceedings of the National Academy of Sciences.

Researchers identify protein linked to tumor invasion

70652986 — Mon, 26 Mar 2007 05:21:30 -0400

Metastasis occurs when cancer cells penetrate the boundaries of the tumor's tissue and infiltrate the walls of blood vessels or lymph vessels, gaining a means of transport to other parts of the body –- far from the original tumor site –- where they can then grow anew. This process is unique to cancer cells and is what makes the disease so dangerous –- and so feared. “A primary [cancerous] tumor can be removed,” explains the senior author of a new study, Alex Toker, of Beth Israel Deaconess Medical Center and assistant professor at Harvard Medical School. “But once the cancer has metastasized, it becomes intractable.” Scientists have known that in order for a tumor to metastasize, certain genes had to be “turned on” so that they could produce enzymes necessary to invade blood vessel walls and penetrate other tissues. New research has found that a protein known for its role in helping to provide the body's immune system with a line of defense against infection is also in cancer cells that were removed from aggressive carcinomas of the breast and colon. This discovery could provide scientists with a promising new target for the development of a drug to halt tumor invasion and metastasis.

RNA technology thwarts HIV

70652986 — Mon, 26 Mar 2007 05:22:05 -0400

RNA interference (RNAi) is a naturally occurring phenomenon by which cells guard themselves against viruses. The process involves post-transcriptional gene silencing in which specific RNA sequences get chopped into small pieces after binding to complementary short interfering RNAs (siRNA). These siRNAs can target either host mRNAs or viral genomic or messenger RNAs. As a consequence, gene expression and protein synthesis are blocked, inhibiting viral infection. Researchers at Harvard Medical School and the Massachusetts Institute of Technology have used RNA interference to inhibit HIV infection in host cells, raising hopes that the technology can be developed to complement available antiretroviral therapies. "It is interesting that this ancient, natural defense mechanism against viruses can be harnessed against HIV," said Premlata Shankar, an HMS assistant professor of pediatrics at the Center for Blood Research and a lead author on the study, which appeared in print in the July 2002 issue of the journal Nature Medicine.

Lack of protein ApoE in brain may raise Alzheimer's risk

70652986 — Mon, 26 Mar 2007 05:18:29 -0400

Brain cells are protected from possible contamination by substances in circulating blood by what is known as "the blood-brain barrier." Researchers have many questions about precisely how this protective mechanism works. Recently, Harvard Medical Sschool researchers identified a protein that supports the blood-brain barrier. When a molecule, apolipoprotein E (apoE), is absent, the barrier becomes especially porous, making the brain vulnerable to trauma and possibly Alzheimer's disease. Denisa Wagner, Harvard Medical School professor of pathology at the Center for Blood Research and senior author of the study, "wondered whether apoE might be important for the integrity of the brain's vasculature." In a study with mice, her research team found that it was. According to Wagner, this study, published in the December 2001 issue of Molecular Medicine, and two others published recently suggest links between apoE, an impaired blood-brain barrier, and Alzheimer's. Major risk factors for the disease, such as brain injury, age, and high cholesterol, are precisely those that aggravate the increase in blood-brain barrier permeability associated with apoE deficiency.

Remote-control immunity up close

70652986 — Mon, 26 Mar 2007 05:17:52 -0400

When we receive a wound, disease-fighting cells rush to the scene to do combat with bodily invaders. But how does this work? When we receive a wound, cells near the wound send out chemical signals to attract disease-fighting cells. These chemical messengers travel to the lymph nodes in our bodies. The lymph node is, according to Ulrich von Andrian, Harvard Medical School associate professor of pathology at the Center for Blood Research, "the staging area for our fight against infection in the periphery." The whole system operates, according to von Andrian, by "remote control." The research contributes to our understanding of how the immune system works in the body. Von Andrian and his colleagues published their work in the November 2001 issue of the Journal of Experimental Medicine.

Sorting good eggs from bad ones

70652986 — Mon, 26 Mar 2007 05:13:04 -0400

An oocyte is an immature egg cell in the ovaries. Before a woman is born, her ovaries will contain about five million eggs. At birth, about three million of those egg cells die -- apparently by committing suicide. This fact of nature has long puzzled scientists. Now, Harvard researchers working at the Center for Blood Research have uncovered a critical clue that may lead to a greater understanding of infertility and miscarriage. Oocytes are killed by proteins called caspases. Studies in worms have suggested that the caspases are triggered by a unique set of signals in oocytes. But up until now no one has been able to discover those molecular signals. Rosa Navarro, Keith Blackwell, and their colleagues recently identified one such signal -- a defect in a protein needed for processing RNA. In worms lacking the protein, oocytes underwent mass suicide. The findings in worm oocytes could shed light on questions of human concern, such as infertility. "I think we're plugging into something that's involved with what makes a good oocyte," Blackwell said. Being able to distinguish good oocytes from bad could yield information about the potential for birth defects, miscarriages, and infertility.