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:
+ Bone Marrow-Based Immune Cells Kill More Cancer
+ Sirtuin1 Is Critical in Liver's Production of Sugar
+ Sirtuin's Structural Secrets Revealed
NEWS BRIEFS:
"Basics," a Printed Newsletter for the Basic Sciences
"Top 10" Microarray Analysis Seminar April 6
Young Investigators' Day Celebration April 14
AWARDS AND HONORS:
Seydoux and Kolodkin Named HHMI Investigators
Brady Gets Space Biomedical Research Award
IN THE NEWS:
Alex Kolodkin in The Daily Record
Stephen Baylin in the New York Times
Shawn Zack in the Guardian
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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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3/1/05
Bone Marrow-Based Immune Cells Kill More Cancer
In experiments with human cells, Johns Hopkins Kimmel Cancer Center scientists have found that T-cells from bone marrow dramatically outperformed their counterparts from blood when both were "primed" to home in on myeloma, a cancer of the bone marrow.
The marrow-based T-cells identified both mature myeloma cells and the primitive cells responsible for the disease. Activated bone marrow T-cells stopped the growth of 86 percent of myeloma stem cell colonies compared to 47 percent for activated T-cells taken from circulating blood, the researchers report in the March 1 issue of Cancer Research.
"It is very difficult to design cancer therapies that get the body's immune system to recognize and kill cancer cells that the system has ignored for a long time," says Ivan Borrello, MD, assistant professor of oncology and director of the research. "Now, we have evidence that 'educating' T-cells in the bone marrow may be the most effective way to get an anti-tumor response."
http://www.hopkinsmedicine.org/Press_releases/2005/03_01b_05.html
Cancer Research 1 March 2005;65(5):2026-2034.
http://cancerres.aacrjournals.org/cgi/content/abstract/65/5/2026
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3/3/05
Sirtuin1 Is Critical in Liver's Production of Sugar
In the March 3 issue of Nature, Johns Hopkins researchers report that two proteins best known for very different activities actually come together to turn the liver into a sugar-producing factory when food is scarce.
The researchers discovered that, in fasting mice, the liver's production of sugar kicked into high gear because amounts and activities of the two proteins, called sirtuin1 and PGC1-alpha, increased when dietary calories weren't available. Once mice were fed, levels of the two proteins went down and sugar production ceased. The finding is the first to link in mammals processes involved in cellular aging (sirtuin1) and responding to calorie intake (PGC1-alpha), and offer a new target for diabetes-fighting drugs.
"It isn't a coincidence," says Pere Puigserver, PhD, an assistant professor of cell biology at the Johns Hopkins University School of Medicine's Institute for Basic Biomedical Sciences. "The two proteins actually bind to each other, and without sirtuin1, PGC1 can't make glucose."
In their experiments, graduate student Joseph Rodgers also discovered that high levels of pyruvate, a starting material for making glucose, appear to trigger accumulation of sirtuin1 protein in the liver. Rodgers will receive the Nupur Dinesh Thekdi Research Award on April 14 for his work as part of the School of Medicine's 28th annual Young Investigators' Day celebration.
http://www.hopkinsmedicine.org/Press_releases/2005/03_02a_05.html
Nature 3 March 2005;434(7029):113-118.
http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v434/n7029/full/nature03354_fs.html
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3/17/05
Sirtuin's Structural Secrets Revealed
Johns Hopkins researchers have determined how a tiny molecule called nicotinamide normally squelches the activity of Sir2, a.k.a. sirtuin, an enzyme that otherwise could help yeast, worms and flies live longer. The findings are described in the March 18 issue of Molecular Cell.
The structural secrets they uncovered are likely to help efforts to design molecules that increase or decrease the enzyme's normal activity, which is to turn on or off certain proteins by removing acetyl groups from the proteins. The idea isn't to create a fountain of youth, say the researchers, but to help treat diabetes, inflammation, cancer or other conditions in which the enzyme plays a role.
"Some of the proteins the enzyme turns on or off are already known to be involved in disease, and new ones are being identified all the time," says Cynthia Wolberger, PhD, professor of biophysics and a Howard Hughes Medical Institute investigator in Johns Hopkins' Institute for Basic Biomedical Sciences. "The idea is that specifically and carefully altering the activity of sirtuins could help fix those conditions by restoring appropriate activity levels of the specific protein involved."
Nicotinamide, itself a product of the enzyme's complex chemistry, modulates Sir2's deacetylase activity, but exactly how it worked was unknown. The 3-D structures, determined by then-graduate student Jose Avalos, show that nicotinamide is made and binds in just one spot in the enzyme, not two different places as had been proposed by others.
http://www.hopkinsmedicine.org/Press_releases/2005/03_18_05.html
Molecular Cell 18 March 2005;17(6):855-868.
http://dx.doi.org/10.1016/j.molcel.2005.02.022
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"Basics," a Printed Newsletter for the Basic Sciences -- The Institute for Basic Biomedical Sciences has launched "Basics," a printed newsletter on issues relevant to the basic science research community at the Johns Hopkins School of Medicine. "Basics" currently appears as an insert in the first issue of the month of Change, a publication for faculty and senior staff at the medical school. Deborah Rudacille, Marjorie Centofanti, Patrick Gilbert and Joanna Downer are the writers and editors involved in the project. Look for the third issue of "Basics" in early April. Read the first two online from a Hopkins computer at:
http://www.insidehopkinsmedicine.org/change/011205/basics.cfm
http://www.insidehopkinsmedicine.org/change/021605/basics.cfm
"Top 10" Microarray Analysis Seminar Apr. 6 -- The eighth installment of the Seminar Series: Top 10 Things To Know in Microarray Analysis will be presented Wednesday, April 6, starting at 2:30 p.m. in the Becton Dickinson Hall W1020 in the Bloomberg School of Public Health. The lecture, "Supervised Clustering," will be presented by Elizabeth Garrett-Mayer, PhD, of the Biostatistics Program at the Johns Hopkins Kimmel Cancer Center. This seminar series is sponsored by the JHMI Microarray Core Facility, The Hopkins Expressionists (JHSPH) and The Department of Biostatistics, JHSPH. For more information, email seminar@microarray.jhmi.edu.
http://www.microarray.jhmi.edu/seminar
Young Investigators' Day Celebration April 14 -- The 28th annual Young Investigators' Day celebration at the School of Medicine will be held April 14, starting at 4 p.m. in Mountcastle Auditorium in the Preclinical Teaching Building. Student awardees Jeffrey Han, Christopher Brett, David Maag, Jr., and Kara Lassen and postdoctoral awardees Chenghua Gu, PhD, and Sunil Karhadkar, MD, will give lectures on their work. All award recipients will host posters on their research at a reception to begin after the lectures and presentation of awards. Young Investigators' Day was established in 1978 to recognize trainees at the School of Medicine and to provide them with a forum for presentation of their work. For a detailed schedule and list of award recipients, visit:
http://www.hopkinsmedicine.org/2005/Press_Releases/YIDschedule
Seydoux and Kolodkin Named HHMI Investigators -- Geraldine Seydoux, PhD, and Alex Kolodkin, PhD, were among 43 new investigators announced by the Howard Hughes Medical Institute on March 21. Seydoux, a professor of molecular biology and genetics, studies cell fate specification during development in the model organism C. elegans. Kolodkin, a professor of neuroscience, studies the attractive and repulsive signals that direct growing nerves toward their intended targets. Including Seydoux and Kolodkin, there are currently 14 HHMI investigators at Hopkins.
http://www.hhmi.org/news/032105.html
http://www.hhmi.org/news/seydoux.html
http://www.hhmi.org/news/kolodkin.html
Brady Gets Space Biomedical Research Award -- The Laurence R. Young Space Biomedical Research Award for 2005 has been presented to Joseph V. Brady, PhD, professor of behavioral biology and director of the Behavioral Biology Research Center on the Johns Hopkins Bayview campus. The award, given jointly by the National Space Biomedical Research Institute (NSBRI) and the National Aeronautics and Space Administration, recognizes Brady "for pioneering space research on animal and human behavioral neuroscience and outstanding service to the space biomedical research community." Brady, who also holds a joint appointment in Hopkins' Department of Neuroscience, is Neurobehavioral and Psychosocial Factors Associate Team Leader for NSBRI. He has also recently been awarded the Cambridge Center Award for Distinguished Contribution to the Scientific Study of Behavior and FASEB's Lifetime Scientific Achievement Award.
Alex Kolodkin on selection as an HHMI investigator (with Geraldine Seydoux) in The Daily Record: "Two Hopkins researchers win funding and freedom," by Robyn Lamb, The Daily Record, March 28, 2005.
http://www.jhu.edu/clips/2005_03/28/two.html (must be at a Johns Hopkins computer for access)
Stephen Baylin on the proposed cancer genome project in the New York Times: "In Battling Cancer, a Genome Project Is Proposed," by Andrew Pollack, the New York Times, March 28, 2005.
http://www.jhu.edu/clips/2005_03/28/battling.html (must be at a Johns Hopkins computer for access)
Shawn Zack on the North American origin of Afrotheria in the Guardian: "Out of Africa: Something Shrew," The Guardian, March 24, 2005.
http://www.guardian.co.uk/life/dispatch/story/0,12978,1444219,00.html
http://www.jhu.edu/clips/2005_03/24/africa.html (must be at a Johns Hopkins computer for access through this link)
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Find "Change" and "Basics" online from a Hopkins computer:
http://www.insidehopkinsmedicine.org/change
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"
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--JHMI--
