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 (4-5105, jdowner1@jhmi.edu).
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IN THIS ISSUE:
+ Scientists Discover How NO Prevents Blood Vessel Inflammation
+ Better Animal Model Sheds Light on Potential Angiogenesis Target
+ Embryonic Pathway Critical To Growth of Digestive Tract Tumors
NEWS BRIEFS:
Agre to Give Nov. 25 Lecture
Broadway Research Building Opens
Hirschi to Present Vascular Cell Engineering Seminar Dec. 5
University-Wide Conflict of Interest Training Deadline Dec. 31
AWARDS AND HONORS:
Gearhart Honored by Medical Research Organization
Poynton Named Guest Professor by German Research Council
Cardiology Fellows Ardehali and Roguin Win First Prizes
Ladenson to Edit Major Endocrinology Journal
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10/17/03
Scientists Discover How NO Prevents Blood Vessel Inflammation
Johns Hopkins scientists investigating the molecular messenger nitric oxide (NO) have figured out how it can block blood vessel inflammation and prevent clotting.
Reporting in the Oct. 17 issue of Cell, Charles Lowenstein, MD, and his team observed that NO has the power to inhibit endothelial cells' release of inflammatory substances.
Normally, these cells activate a process called exocytosis to start vascular inflammation: packets of molecules are released into the bloodstream that, like tiny hand grenades, explode and discharge compounds that trigger inflammation. NO can enter the endothelial cell and stop exocytosis by targeting a protein, N-ethylmaleimide-Sensitive Factor (NSF), blocking the ability of NSF to push out the molecules.
"Nitric oxide may regulate exocytosis this way in a variety of diseases," says Lowenstein, an associate professor of medicine. "For example, nitric oxide blocks exocytosis from platelets, preventing blood clots; exocytosis from neurons, decreasing neurotoxicity in strokes; and exocystosis from lymphocytes, reducing autoimmune damage."
In experiments with human endothelial cells in culture, NO blocked the release of inflammatory compounds. Furthermore, platelets stuck to blood vessels more often in mice that could not make NO, compared to normal mice, the researchers report.
Already, Lowenstein's team has developed a potential anti-clotting drug -- a peptide that blocks exocytosis by a mechanism similar to that of nitric oxide.
More Info
10/20/03
Better Animal Model Sheds Light on Potential Angiogenesis Target
Johns Hopkins Kimmel Cancer Center researchers have learned that a common, cancer linked gene thought to control blood vessel growth may not turn out to be useful as an effective target for cancer drug development. Their research, published in the Oct. issue of Cancer Cell, shows that results of previous studies that pinned hope on the Id1 gene may not hold up in a mouse model thought to more accurately represent how humans get cancer.
"Clues to promising cancer drug development are only as good as the model in which you study a process," says Rhoda Alani, MD, director of the study and assistant professor of oncology, dermatology and molecular biology and genetics. "If knocking out the Id1 gene in two different models produces two different results, then we need to reevaluate the role that Id1 plays in angiogenesis."
The scientists began their study attempting to confirm previous work, including their own, that suggested Id1 activation was an important step in tumor angiogenesis. In that work, scientists injected tumor cells into mice to stimulate cancer growth. Tumors grew only in the animals whose Id1 gene was activated.
In the new model, mice were exposed to carcinogens placed on their skin and allowed to gradually develop cancer. Surprisingly, mice with the Id1 gene inactivated developed more and larger tumors than in previous studies.
The team's preliminary findings suggest that carcinogen-triggered cancers may develop faster in mice without Id1 because inactivation of the Id1 gene triggers changes in receptors on skin immune cells known as gamma delta T cells.
More Info
Cancer Cell Oct 2003;4:291-299
10/23/03
Embryonic Pathway Critical To Growth of Digestive Tract Tumors
A signal critical for normal embryo development in many species also contributes to cancers of the esophagus, stomach and pancreas in people, according to Johns Hopkins researchers. Upwards of 50,000 cancer deaths a year may now be partly attributable to this pathway's activity, say the researchers, whose report appears in the Oct. 23 issue of Nature.
The signal, called Hedgehog, tells cells when and where to grow during embryonic development and is turned on in primitive cells, or stem cells, in adult tissues to trigger tissue repair.
In experiments with cancer cell lines and tumor samples from patients, the scientists, led by postdoctoral fellow Sunil Karhadkar, PhD, found that Hedgehog's signal is required for the cancers' growth. Moreover, a three-week course of a plant-derived chemical called cyclopamine, known to block Hedgehog, killed a metastatic biliary tract tumor (cholangiocarcinoma) grown in mice, while causing no apparent harm to the animals.
"In mice, blocking the Hedgehog signal made the implanted tumors disappear," says David Berman, MD, PhD, assistant professor of pathology at Hopkins. "It's been about three and a half months since we stopped the cyclopamine, and still the tumors haven't returned."
Hedgehog and its signaling pathway have already been linked to a non-fatal skin cancer (basal cell carcinoma), a deadly lung cancer and the most common childhood brain cancer (medulloblastoma). The signal's broad activation during development, however, indicated it may be involved in a wider variety of cancers that those identified so far, says Berman.
More Info
Nature 2003;425(6960):846-851
See a related News and Views in the same issue:
Hopkins Nobel Winner Agre to Give Nov. 25 Lecture -- Peter Agre, MD, professor of biological chemistry and co-recipient of the 2003 Nobel Prize in Chemistry, will give a lecture, "Aquaporin Water Channels -- From Atomic Structure to Clinical Medicine," starting at 4 pm, Nov. 25, in West Lecture Hall on the ground floor of Wood Basic Science Building. Tea will begin at 3:30 pm.
Broadway Research Building Opens -- Three years in the making, the $140 million, 372,000-square-foot Broadway Research Building opened on the East Baltimore campus of The Johns Hopkins Medical Institutions. Dominating the corner of Broadway and Madison Street, the facility, designed by Payette Associates of Boston, features six floors and 119,300 square feet of advanced biomedical research laboratories used by Comparative Medicine, Medicine and Basic Sciences faculty along with administrative offices and conference rooms.
More Info
Hirschi to Present Vascular Cell Engineering Seminar Dec. 5 -- At 9 am, Friday, Dec. 5, Karen Hirschi, PhD, associate professor of pediatrics and molecular and cell biology at Baylor College of Medicine, will present "Vascular Progenitors in Adult and Embryonic Tissues" as part of the seminar series for the Johns Hopkins Institute for Cell Engineering's Program in Vascular Cell Engineering.
University-Wide Conflict of Interest Training Deadline Dec. 31 -- All University faculty, staff, researchers, students, trainees and administrators (including administrative assistants) must complete the "Conflict of Interest and Commitment" online training module by Dec. 31. The training module is at https://secure.lwservers.net .
http://www.hopkinsmedicine.org/faculty_staff/policies/facultypolicies/coi_training_module.html
Gearhart Honored by Medical Research Organization -- John D. Gearhart, PhD, C. Michael Armstrong Professor of Medicine and professor of gynecology and obstetrics, was honored for his pioneering work with stem cells by the Coalition for the Advancement of Medical Research, Oct. 27, at a ceremony at the National Press Club in Washington, DC.
Poynton Named Guest Professor by German Research Council -- Sarah Poynton, PhD, assistant professor of comparative medicine (part time), has been selected as a 2003 recipient of a Mercator Guest Professorship from the German Research Council (DFG). She will spend several months a year at Humboldt University and the Institute for Freshwater Ecology and Inland Fisheries in Berlin, where she will conduct research on pathogenic protozoan parasites and teach classes in parasitology and scientific communication skills.
Cardiology Fellows Ardehali and Roguin Win First Prizes -- Cardiology fellows Hossein Ardehali, MD, PhD, and Ariel Roguin, MD, PhD, received first place accolades at the Ninth Annual National AstraZeneca Cardiovascular Young Investigators' Form, held in Savannah, Oct. 16-19. Ardehali was honored in the basic science competition for his project "Multiprotein complex containing succinate dehydrogenase confers mitochondrial ATP sensitive K+ channel activity." Roguin was recognized for his project "Modern pacemaker and implantable cardioverter defibrillator systems can be MRI safe" in the clinical competition.
Ladenson to Edit Major Endocrinology Journal -- Paul Ladenson, MD, professor in the Division of Endocrinology in the Department of Medicine, has been selected to become the next editor-in-chief of the Journal of Clinical Endocrinology and Metabolism, for five years, beginning January 2005.
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