This is the twice-per-month electronic newsletter for basic, preclinical and translational research news related to the Johns Hopkins School of Medicine. Please forward freely. Direct comments or questions to Joanna Downer, PhD, in the Office of Corporate Communications (410-614-5105, jdowner1@jhmi.edu).
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IN THIS ISSUE:
+ IL-6 Is a Likely Cause of Transverse Myelitis and Similar Diseases
+ Sugar Helps Control Cell Division
+ Hopkins Scientists Uncover "Tags" that Force Proteins to Cell Surface
+ Study: Tyrosine Kinases Could Be Targets for Brain Cancer Treatment
+ Cancer Drug Might Help Kids With Fatal "Aging" Syndrome
NEWS BRIEFS:
Ethics and Animal Welfare Lecture Oct. 17
Professional Development Seminars Oct. 19, Nov. 11
100+ Women Professors Symposium Nov. 1
Jews in Medicine Conference Nov. 6 in NYC
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Do you have an interesting research finding about one month from publication or presentation? Send manuscripts to Joanna Downer at jdowner1@jhmi.edu or fax to 410-614-8951. Information about awards and honors received by laboratory personnel and others is welcomed also.
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RESEARCH HIGHLIGHTS:
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9/22/05
IL-6 Is a Likely Cause of Transverse Myelitis and Similar Diseases
Johns Hopkins researchers have discovered that the immune cell messenger interleukin-6 is a cause of transverse myelitis, a paralyzing autoimmune disease of the central nervous system and a relative of multiple sclerosis.
In the October issue of The Journal of Clinical Investigation, the researchers report that levels of IL-6 are elevated in the spinal fluid of patients with TM and correlate with the severity of paralysis. Using cell culture and animal studies, the researchers confirmed that elevated IL-6 levels directly injured the spinal cord.
"This is the first time a single culprit has been identified as causing an autoimmune disease of the central nervous system," says Adam Kaplin, MD, PhD, an assistant professor of psychiatry at Johns Hopkins.
Under the microscope, tissue from IL-6-infused rats showed demyelination and injury of axons, pathology nearly identical to that seen in people with TM, says Douglas Kerr, MD, PhD, an assistant professor of neurology and director of the Transverse Myelitis Center at Johns Hopkins.
http://www.hopkinsmedicine.org/Press_releases/2005/09_22a_05.html
J Clin Invest Oct. 2005;115(10):2731-2741.
http://www.jci.org/cgi/content/full/115/10/2731
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9/23/05
Sugar Helps Control Cell Division
Johns Hopkins scientists have discovered that a deceptively simple sugar is in fact a critical regulator of cells' natural life cycle.
The discovery reveals that, when disturbed, this process could contribute to cancer or other diseases by failing to properly control the steps and timing of cell division, the researchers say. The findings are described in the Sept. 23 issue of the Journal of Biological Chemistry.
The sugar, known as O-GlcNAc (pronounced oh-GLUCK-nack), is used inside cells to modify proteins. The sugar's comings and goings seem to be important controllers of cell division, say the researchers.
"The dogma for decades has been that the cycle of cell division is controlled by the appearance and disappearance of certain proteins called cyclins, but experiments have shown that you can knock out any of these and still get perfectly normal cell division," says the study's first author, Chad Slawson, PhD, a postdoctoral fellow in biological chemistry in Johns Hopkins' Institute for Basic Biomedical Sciences.
"In contrast, our experiments show that by increasing or decreasing the amount of sugar attached to proteins, the cell cycle is disrupted and isn't salvageable unless O-GlcNAc levels are fixed," he says.
The exact nature of cells' problems depended on whether O-GlcNAc levels on proteins were too high or too low, adds Gerald Hart, PhD, professor and director of biological chemistry.
http://www.hopkinsmedicine.org/Press_releases/2005/09_20_05.html
J Biol Chem 23 Sept. 2005;280(38):32944-32956.
http://www.jbc.org/cgi/reprint/M503396200v1
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9/24/05
Hopkins Scientists Uncover "Tags" that Force Proteins to Cell Surface
Johns Hopkins scientists have discovered internal "shipping labels" that allow -- and perhaps force -- hundreds if not thousands of proteins to get to the surface of cells and stay there. Two natural proteins that use one of these "tags" are the ion channel that lets heart cells contract on cue, and the docking point that allows HIV, the virus that causes AIDS, into cells, the researchers discovered.
Because proteins on the cell surface are binding sites for drugs and other molecules, as well as triggers of immune reactions, the findings, described in the Oct. 1 issue of Nature Cell Biology, might revolutionize efforts in drug and vaccine development, says the Hopkins team.
"If we can force proteins to the cell surface, we can overcome obstacles that have prevented laboratory study of some really important proteins," says the study's senior author, Min Li, PhD, a professor of neuroscience at the High Throughput Biology Center of the Johns Hopkins' Institute for Basic Biomedical Sciences. The application of these surface tags to force protein transportation to the cell surface is the subject of a Patent Cooperation Treaty (PCT) patent application submitted by The Johns Hopkins University.
From among 25 billion randomly created, eight-building-block-long protein bits, postdoctoral fellow Sojin Shikano uncovered 65 that forced a normal protein to leave the cell's protein-building factory and go to the cell surface. The researchers then uncovered human proteins that use variations of the most potent tag they'd found, dubbed SWTY.
http://www.hopkinsmedicine.org/Press_releases/2005/09_22_05.html
Nature Cell Biology 1 Oct. 2005;7(9):985-992.
http://www.nature.com/ncb/journal/v7/n10/full/ncb1297.html
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9/26/05
Study: Tyrosine Kinases Could Be Targets for Brain Cancer Treatment
Researchers at Johns Hopkins, the J. Craig Venter Institute and elsewhere have identified three new genetic mutations in two tyrosine kinases, a discovery that could pave the way for more effective treatment of brain tumors.
By studying cells from 19 patients with glioblastoma, the researchers discovered mutations in two tyrosine kinase proteins already known to disrupt normal cell activity and contribute to several other cancers, such as colorectal, breast and ovarian cancer, chronic myelogenous leukemia, gastrointestinal stromal tumors and lymphoma.
"We picked these proteins to sequence because receptor tyrosine kinases sit on the cell surface where anticancer drugs can get at them," says Gregory Riggins, MD, co-lead author of the study and an associate professor of neurosurgery at Johns Hopkins.
Two new mutations were found in fibroblast growth receptor-1, and one new mutation in platelet derived growth factor receptor-alpha, the researchers report in the Oct. 4 issue of the Proceedings of the National Academy of Sciences.
http://www.hopkinsmedicine.org/Press_releases/2005/09_26_05.html
PNAS 4 Oct. 2005;102(40):14344-14349.
http://www.pnas.org/cgi/content/full/102/40/14344
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9/26/05
Cancer Drug Might Help Kids With Fatal "Aging" Syndrome
Johns Hopkins scientists have discovered that a drug currently being tested against cancers might help children with a rare, fatal condition called Hutchinson-Gilford progeria syndrome, which causes rapid, premature aging. There's no known treatment.
But the new Hopkins research, and similar results from other labs, shows that a class of drugs known as farnesyl transferase inhibitors, or FTIs, can reverse an abnormality in laboratory-grown cells engineered to mimic cells from progeria patients. Such cells have nuclei that aren't round like normal nuclei but instead have multiple "lobes" and can even look like a cluster of grapes or bubbles.
In the laboratory, however, treating these engineered cells with an FTI already in clinical trials in cancer patients restored the cells to a normal appearance, the researchers report in the Oct. 4 issue of the Proceedings of the National Academy of Sciences.
The drug blocks the first step in processing the faulty protein that causes the syndrome, says Susan Michaelis, PhD, professor of cell biology at Johns Hopkins' Institute for Basic Biomedical Sciences. She emphasizes that no one knows yet whether making the cells' nuclei look normal will be enough to reverse the disease process or slow it down.
http://www.hopkinsmedicine.org/Press_releases/2005/09_26b_05.html
PNAS 4 Oct. 2005;102(40):14416-14421.
http://www.pnas.org/cgi/content/full/102/40/14416
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NEWS BRIEFS:
Ethics and Animal Welfare Lecture Oct. 17 -- Bernard Rollin, PhD, University Distinguished Professor of Philosophy at Colorado State University, will give the next talk in the Enhancing Humane Science Lecture Series on Monday, Oct. 17, starting at 4 p.m. in the Anna Baetjer Room, W1030, in the Bloomberg School of Public Health. Rollin's talk is "Sociology of Ethics, Animal Welfare and Genetically Engineered Animal Models of Human Genetic Disease." The lecture series is sponsored by The Johns Hopkins Center for Alternatives to Animal Testing and the JHU Associate Provost for Animal Research and Resources. For more information contact mprincip@jhsph.edu .
Professional Development Seminars Oct. 19, Nov. 11 -- The Professional Development Office (PDO) is offering their "Giving a Research Talk" workshop on Oct. 19 and the "Writing a Biomedical Research Paper" workshop on Nov. 11. These workshops are designed for new or junior faculty and postdoctoral fellows. Both workshops are held 8:30 a.m. until 4 p.m. The $750 registration fee for each workshop is payable via tuition remission for faculty; the fee for postdoctoral fellows is $375. In December, the PDO is once again offering its multi-day grant writing workshop for new or junior faculty.
http://www.hopkinsmedicine.org/pdo
100+ Women Professors Symposium Nov. 1 -- At a symposium Nov. 1, The Johns Hopkins University School of Medicine will be celebrating the promotion of more than 100 women to the rank of Full Professor since its founding in 1893. All are invited to the celebration, which will include a day of scientific lectures by internationally acclaimed women scientists including a keynote address by the co-recipient of the 2004 Nobel Prize in Medicine, Linda Buck, and a panel discussion including Catherine DeAngelis, editor-in-chief of the Journal of the American Medical Association, and Cokie Roberts, ABC News. Registration is free and required. To review the program and to register, visit:
http://100womengala.onc.jhmi.edu/
Jews and Medicine Conference Nov. 6 in NYC -- The YIVO Institute for Jewish Research at the Center for Jewish History (15 West 16th Street, New York City), in association with the New York Academy of Medicine, is hosting a national conference entitled "Jews and Medicine -- In the Footsteps of Maimonides: The Jewish Doctor as Healer, Scientist and Intellectual," on Sunday, Nov. 6. The conference will run from 9 a.m. until 6 p.m. and is open to healthcare professionals, interns, residents, students and the public. Nine leading medical experts and researchers will explore the history of Jews in medicine and the roles and responsibilities of Jews in the medical field. Registration is $75, or $15 for students, interns and residents. For more information and online registration, visit:
http://www.yivo.org/events/index.php?tid=113&aid=285
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--JHMI--
