JHM Science e-Newsletter Vol. 4, No. 21, Nov. 16, 2004

JHM Science e-Newsletter   Vol. 4, No. 21, Nov. 16, 2004

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).
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

IN THIS ISSUE:

RESEARCH HIGHLIGHTS:

+ Demethylation Agents Turn Off as Many Genes as They Turn On

+ Mouse Study: "Critical" Down Syndrome Region Isn't

+ Human Spinal Cord Cells Help Rats With Lou Gehrig's Disease

+ Olfactory Bulb Stem Cells and Lou Gehrig's Disease

+ Mouse Study: Signal Overload in Alzheimer Brains

NEWS BRIEFS:
   Signal Transduction Symposium Nov. 16 at Hopkins
   Ronnett Gives Nov. 22 Dean's Lecture on Energy Metabolism
   Funding for Prostate Cancer Research
   Update Your Printed Directory Listing

HONORS AND AWARDS:
   Clements To Chair NIH Study Section
   Kolodkin Receives NIH Javits Award
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

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.
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

RESEARCH HIGHLIGHTS:
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
10/18/04
Demethylation Agents Turn Off as Many Genes as They Turn On

Agents believed to selectively "restart" genes that limit cancer's growth -- a potential treatment option already in early clinical studies -- instead turn off as many genes as they turn on, a team of researchers from the National Cancer Institute and Johns Hopkins has discovered.

"We don't know what effect all these changes might have, but it's clear that when scientists are looking only at the agents' effects on a particular gene or a few particular genes, they aren't seeing the whole picture," says Andrew Feinberg, MD, MPH, King Fahd Professor of Medicine. Their report appears in the October issue of Cancer Cell.

The research team probed the global effects on a colon cancer cell line of each of three approaches to unhooking methyl groups from genes' DNA -- 5-aza-2'-deoxycytidine, trichostatin A, and genetic knockouts. Cells normally use methyl groups to "mark" certain genes, indicating whether their instructions should or shouldn't be used for making proteins, but the marks are frequently disrupted in cancer cells.

The new findings don't mean automatic failure for clinical trials of so-called demethylation agents, but they do indicate that careful attention should be paid to results of laboratory experiments and clinical trials that use the agents, since so many genes are affected, says Feinberg.
http://www.hopkinsmedicine.org/Press_releases/2004/10_18_04.html

Cancer Cell Oct 2004;6(4):361-371.
http://www.cancercell.org/content/article/fulltext?uid=PIIS1535610804002685
http://dx.doi.org/10.1016/j.ccr.2004.08.029
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
10/21/04
Mouse Study: "Critical" Down Syndrome Region Isn't

A particular genetic region long assumed to be a critical factor in Down syndrome isn't nearly as important as once thought, Johns Hopkins researchers report in the Oct. 22 issue of Science.

Their studies of genetically engineered mice shred a 30-year-old notion that genes in this region are largely responsible for the condition's characteristic facial features and some of its other common traits.

"If anyone is going to try to treat the problems seen in Down syndrome, we need to understand what is really happening and when in development it happens," says Roger Reeves, PhD, professor of molecular biology and genetics in Johns Hopkins' Institute for Basic Biomedical Sciences and McKusick-Nathans Institute of Genetic Medicine. 

Down syndrome occurs when three copies of chromosome 21 are present in a fertilized egg, although rare cases occur when just a section of the chromosome is found in triplicate, a situation called segmental trisomy. A small region of this replicated segment is found in triplicate in all people with segmental trisomy and Down syndrome's facial features, and so it had been dubbed the "Down syndrome critical region" or DSCR.

However, then-graduate student Lisa Olson, PhD, found that mice with three copies of just their DSCR equivalent actually had facial and skeletal changes opposite of those seen in Down syndrome. Moreover, mice with just two copies of DSCR but three copies of the rest of the chromosome did have the shorter bones characteristic of Down syndrome.
http://www.hopkinsmedicine.org/Press_releases/2004/10_21a_04.html

Science 22 Oct 2004;306(5696):687-690.
http://www.sciencemag.org/cgi/content/full/306/5696/687

See a related News and Views:
Science 22 Oct 2004;306(5696):619-621.
http://www.sciencemag.org/cgi/content/full/306/5696/619
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
10/23/04
Human Spinal Cord Cells Help Rats with ALS

Johns Hopkins researchers have found that transplants of mouse stem cells taken from the adult brain's olfactory bulb can delay symptoms and death in a mouse model of amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease. The findings were presented Oct. 24 at the annual meeting of the Society for Neuroscience in San Diego.

The olfactory bulb, the center of smell detection, houses numerous primitive stem cells that normally feed the constant, life-long regeneration of odor-detecting nerves. Because they are found in a fairly accessible region of the brain and could conceivably be removed from a person's olfactory bulb without causing permanent damage, adult olfactory bulb stem cells are a potential non-embryonic source for cells that could prove useful in replacing nerve cells lost due to injury or diseases like ALS and Parkinson's.

Researchers Zhiping Liu, PhD, and Lee Martin, PhD, grew clusters of neuronal stem cells taken from the olfactory bulb of normal mice and froze them. Retrieved cells were then transplanted into the spinal cords of genetically engineered mice that develop the equivalent of ALS.

Animals that got the transplanted cells developed disease symptoms about a month and a half later than non-transplanted animals and lived about two months longer.
http://www.hopkinsmedicine.org/Press_releases/2004/10_24_04.html

Read the abstract
http://sfn.scholarone.com/itin2004/main.html?new_page_id=126&abstract_id=4763&p_num=134.6&is_tech=0
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
10/25/04
Mouse Study: Signal Overload in Alzheimer Brains

In studies with mice that develop the equivalent of familial Alzheimer's disease, Johns Hopkins researchers have shown that brain cells' signals confuse the movement of implanted neuronal stem cells.

The observation reinforces the idea that disease can create "microenvironments" that affect the behavior of cells. These local environments might help recruit stem cell-based therapies in other conditions, say the researchers. The findings were presented Oct. 25 at the annual meeting of the Society for Neuroscience by first author Zhiping Liu, PhD, a research associate in pathology.

"In normal adult mice, stem cells taken from the olfactory bulb returned to the olfactory bulb -- they returned to where they belong -- even though they had come from a different mouse," says Lee Martin, PhD, associate professor of pathology and neuroscience at Hopkins. "In mice with Alzheimer's disease, the stem cells went all over the place within the brain, responding to a multitude of signals whose identities we don't even know."

Remarkably, Martin says, the stem cells were attracted to the abnormal protein bundles called amyloid plaques that cause Alzheimer's, possibly opening the door to delivering some sort of plaque-buster.
http://www.hopkinsmedicine.org/Press_releases/2004/10_25a_04.html

Read the abstract
http://sfn.scholarone.com/itin2004/main.html?new_page_id=126&abstract_id=8208&p_num=488.10&is_tech=0
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

 NEWS BRIEFS:

Signal Transduction Symposium Nov. 16 at Hopkins -- The Sidney Kimmel Comprehensive Cancer Center will hold a day-long symposium, "Signal Transduction: From Development to Disease," in Hurd Hall, Tuesday, Nov. 16, from 8 am to 4 pm. Experts from Johns Hopkins and elsewhere will share research results and provide suggestions on how to translate developments in signal transduction research into new approaches to treatment and prevention of human diseases. Register for this symposium at http://oncweb1.onc.jhmi.edu/stSymposium .
http://www.insidehopkinsmedicine.org/news/news_detail.cfm?id=2479

Ronnett Gives Nov. 22 Dean's Lecture on Energy Metabolism -- Gabriele Ronnett, MD, PhD, professor of neuroscience and of neurology will give the first Dean's Lecture of the academic year beginning at 5 pm, Monday, Nov. 22, in Hurd Hall. Her lecture is titled "Energy Wars: Fatty Acid Synthase as a metabolic energy sensor and its role in the treatment of cancer, obesity and stroke."
http://www.insidehopkinsmedicine.org/news/news_detail_page.cfm?id=2557

Funding for Prostate Cancer Research -- Funding is available to support multidisciplinary research in prostate cancer through the Patrick C. Walsh Prostate Cancer Research Fund and the Johns Hopkins SPORE program.  Awards of $50,000 to $100,000 for up to 2 years are available to fund career development and developmental research programs (pilot projects).  The deadline for applications is Friday, Jan. 7, 2005.
http://prostatecancerprogram.onc.jhmi.edu/

Update Your Printed Directory Listing -- The 2005 edition of the Johns Hopkins Institutions' printed faculty and staff telephone directory will be published soon. You may review and update or correct your personal listing by using your JHED username and password to log on to http://printeddirectory.johnshopkins.edu . The deadline to make changes to your printed listing is Nov. 25. Updating the printed directory information does not update any other directory. To update information in the online JHED directory, log onto http://jhed.johnshopkins.edu and click "Change My Info."

HONORS AND AWARDS:

Clements To Chair NIH Study Section -- Janice Clements, PhD, professor and director of comparative medicine, will serve as chairperson of the NeuroAIDS and Other End-Organ Diseases Study Section of the Center for Scientific Review at the National Institutes of Health. According to the acting director of the CSR, Clements was selected based on her demonstrated competence and achievement in her scientific discipline. Clements heads the Retrovirus Laboratory, providing leadership for faculty in an integrated research program on the pathogenesis of lentivirus infections with emphasis on animal models of AIDS dementia and central nervous system (CNS) disease. Her own laboratory's work focuses on using simian immunodeficiency virus (SIV) to examine the molecular basis for the pathogenesis of HIV CNS disease. Clements also is professor of neurology and of pathology, holds a joint appointment in molecular biology and genetics, and is vice dean for faculty affairs.
http://www.csr.nih.gov/Review/AARRIRG.htm#NAED
http://www.hopkinsmedicine.org/comparativemedicine/faculty/clements.html

Kolodkin Receives NIH Javits Award -- Alex Kolodkin, PhD, professor of neuroscience in Hopkins' Institute for Basic Biomedical Sciences, has been named one of eight recipients of this year's Senator Jacob Javits Award from the National Institute of Neurological Diseases and Stroke. The award, which provides for up to 7 years of funding, was created in 1983 to honor Javits, who had amyotrophic lateral sclerosis and was a strong advocate for research on a variety of neurological disorders. Investigators are nominated by NINDS staff from a pool of competing grant applicants. Kolodkin is studying how proteins called semaphorins and their binding partners guide the tentacle-like axons that extend from nerve cells during development. This work has implications for nerve regeneration, tumor development and immune system function.
http://www.ninds.nih.gov/news_and_events/news_articles/news_article_javits_20041110.htm_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

Visit the "Research WebNotes" newsletter online:
http://www.hopkinsmedicine.org/webnotes/

For more news from Hopkins, see:
http://www.hopkinsmedicine.org/Press_releases/index.html

Upcoming lectures and seminars:
http://www.hopkinsmedicine.org/faculty_staff/scicalendar.html

Have you or your colleagues been quoted? Check out
http://www.insidehopkinsmedicine.org and click on "News Clips"
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

--JHMI--