Ft Detrick Spring Research Festival

Just a reminder that the Annual Spring Festival is being held again this year at the Fort on Wednesday and Thursday this week (May 14th & 15th).

The event is open to the public, you just need to tell the armed guards ou’re going to the Spring Festival or the “Tent Show”.

If you’ve never been there, it’s definitely worth a couple hours time, either chatting with the vendors or Poster presenters. This year appears to be unusual because it seems like every year there is either torrential downpour, oppressive heat and even worse, both in combination. Standing in that tent is not pleasant in 100% humidity and 100 degrees.

I also like the theme this year: The Cancer Tree. They will be giving out free seeds, although it appears you’ll have to be a presenter or a exhibitor.

Here’s the story on the tree:

The Cancer Tree (Camptothecaacuminata)Our Spring Research Festival tradition is to choose something found in nature—plant or animal—that produces substances shown to have biochemical activity in fighting or preventing disease. In past years, we have featured the rosy periwinkle of Madagascar, Catharanthus roseus , the marine cone snail, Conus textilis, the African clawed frog, Xenopus laevis, the honeybee, Apis mellifera, and the gila monster (Heloderma suspectum and H. horridum). The “Cancer Tree,” a member of the tupelo family, is known by several additional non-scientific names: the Happy Tree and the Tree of Life. Those names are honestly earned. This is the tree that gave us the anticancer compound camptothecin, a substance found in the tree’s bark. The resulting drugs, topotecan and irinotecan hydrochloride are useful in treating breast cancers, ovarian cancer, colon cancer, malignant melanoma, small cell lung cancer, thyroid cancers, lymphomas and leukemias. The compounds, which have antiviral as well as anti-tumor properties, are also used for the treatment of AIDS. In 2002, the FDA approved another compound similar to topotecan as second-line therapy for certain cervical ovarian and lung cancers. The new compound, through regulating gene expression, can block growth of blood vessels that tumor cells need to survive. The tumor, deprived of its blood supply, can then shrink and die. The National Cancer Institute’s Developmental Therapeutics Program is responsible for the find. Giovanni Melillo, MD, together with colleagues Robert Shoemaker, PhD, and Nick Scudiero, PhD, devised a high-throughput screen for 2,000 compounds and found three other effective compounds in addition to the topotecan analog. The Cancer tree is native to China, growing up to 75 feet tall in warmer climates. In climates such as Maryland, the tree is easily grown from seed and can be kept indoors with ample warmth and bright light, when pruned to manageable size. The Spring Research Festival organizers, in a nod to both the cancer tree and to fostering biodiversity for the sake of research have ordered a supply of Camptotheca acuminata seeds, and will be awarding them to Festival participants. The recipients will receive instructions along with their botanic treasures to ensure that both have the best chances to live long and prosper.

USAMRIID Teams with Hopkins for Graduate degree at Ft Detrick

This looks like a pretty good opportunity for our “younger” readers out there.  The Job Search page continues to be one of the most popular on this site and I often wonder how many of these inquiries are from recent graduates?

In any event I saw a brief note in the FNP today and then pulled the original press release from Hopkins web site.  Here’s the skinny:

JHU Biotech Program, U.S. Army Enter
Collaborative Relationship
Agreement will expand educational opportunities in
biodefense research field

The Johns Hopkins University and the U.S. Army have agreed to work together to train scientists to develop vaccines and medicines to defend against biological attacks.

Students accepted into the program will study part-time to earn Johns Hopkins Master of Science in Biotechnology degrees with concentrations in biodefense. Simultaneously, they will work for the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), located at Fort Detrick, Md.

Under a five-year agreement between Johns Hopkins’ Advanced Biotechnology Studies Program and USAMRIID, graduate students will be employed under the Army’s Student Career Experience Program and will be eligible for Army reimbursement of their Johns Hopkins tuition.

“Based on a long history of excellence in biotechnology research and education at both institutions, this is an invaluable cooperative effort that will significantly enhance the educational opportunities of our biodefense students,” said Richard McCarty, chair of the Advanced Biotechnology Studies program in the university’s Krieger School of Arts and Sciences Advanced Academic Programs. “We hope it will lead to future interactions and joint scientific research between our respective faculty and scientists.”

Johns Hopkins advisors will work with students to select an appropriate course structure that will capitalize on the resources being offered by USAMRIID, such as research staff and laboratory facilities.

USAMRIID does basic and applied research on biological threats to develop vaccines, drugs and tests to protect soldiers, but much of the science it produces is also applied to civilian medicine.

“USAMRIID is very excited about sponsoring these master’s students and offering them the opportunity to work at USAMRIID on vaccines and therapeutics against extremely interesting pathogens,” said Peter Hobart, USAMRIID’s science director. “This is one more manifestation of the institute’s keen interest in working closely with colleges and universities to train the next generation of scientists.”

About the Advanced Biotechnology Studies part-time Master of Science in Biotechnology Program: Grounded in biochemistry, molecular biology, and cell biology, this program allows students to delve into pure science, applied science, lab science, regulatory affairs, and biotechnology enterprise. They can pursue a general master’s in biotechnology or focus on one of three concentrations that are available fully online: bioinformatics, biotechnology enterprise, or regulatory affairs. Concentrations in biodefense and molecular targets and drug discovery require some on-site instruction.

For more information about Johns Hopkins’ part-time graduate degree available through the Advanced Biotechnology Studies Program, please visit biotechnology.jhu.edu or contact our academic advisors:

Patrick Cummings, Senior Associate Program Chair Biotechnology 410-516-4724; cupat@jhu.edu

Dr. Kristina Obom, Associate Program Chair Biotechnology/Bioinformatics 301-294-7159; kobom@jhu.edu

Lynn Johnson Langer, Senior Associate Program Chair Biotechnology (MS/MBA, Bioscience Regulatory Affairs, and Biotechnology Enterprise) 301-294-7063; ljlanger@jhu.edu

My 100th Post: Marligen Makes a Deal

It’s been a while since I’ve heard anything about Marligen, the only Biotech company in my home town of Ijamsville. And even though they are less than a mile from the Montgomery County line, they’re still a FredCoBio member. That’s like having a semi-sterile cell culture flask, I guess. Here’s the news clip, via businesswire.com:

Marligen Exclusively Licenses Genisphere Labeling Technology for the Detection of microRNAs on the xMAP® Platform

Marligen Launches Vantage™ Line for the Purification, Labeling and Detection of microRNAs

IJAMSVILLE, Md.–(BUSINESS WIRE)–Marligen Biosciences, Inc., a supplier of innovative products for the life sciences research market, will become the exclusive provider of Genisphere’s biotinylated labeling kits for detection of microRNAs on the xMAP^® multiplex platform. The microRNA labeling kits using Genisphere Inc.’s 3DNA^™ dendrimer signal amplification technology will be an integral product to Marligen’s new offering supporting researchers studying microRNAs. The Vantage™ product line includes reagent kits for purifying, labeling and detecting microRNA species.

Genisphere’s unique 3DNA^™ dendrimer technology is based on highly branched DNA structures serving as scaffolds for multiple biotins. The use of Genisphere’s signal amplification technology in combination with the Vantage™ microRNA detection panels offers researchers a fast and cost-effective system to directly profile multiple microRNAs in a single sample. The complete system offers exceptional sensitivity and throughput capabilities of greater than 100 samples in a single day and is compatible with total RNA or enriched RNA including degraded RNA from archived tissues. The initial Vantage™ microRNA Detection Panels are designed for profiling the relative abundance of different microRNA species known to be relevant in oncology. The Vantage™ Products will be launched at the upcoming annual meeting of the American Association of Cancer Research.

“High throughput profiling of MicroRNAs presents a challenge when combining rapid, effective labeling with improved detection sensitivity,” said Dr. Robert Getts, Director of R&D at Genisphere. “The complete Vantage™ package, having integrated our rapid 3DNA™ dendrimer microRNA labeling method with Marligen’s carefully designed detection panels, provides an optimized solution with consistent performance and much needed sensitivity on the xMAP® high-throughput detection platform.”

“Because microRNA play such an important role in tumor development and progression, it is vital we offer researchers innovative tools that allow them to profile these biological markers in archived samples. Our collaboration with Genisphere allows us to provide one of the most rapid and sensitive methods to screen directly from such samples,” said James Lazar, Chief Scientific Officer of Marligen Biosciences. “This will not only advance basic research but should expedite the application of microRNA detection in the diagnosis of cancer.”

It’s strange, because this article couldn’t be more timely. The Founder & CEO, Sherry Challberg, was the one who hired me in April 1988 to move South to Maryland. It’s hard to believe that it has been 20 years ago to this day.

I was working in a lab at the University of Rochester doing papilloma virus research (which supported research leading to a Nobel prize for Micheal Bishop in 1989 and in support of research into Open Reading Frames, which lead to the 1993 Nobel Prize for Sharp & Roberts and also 1989 Nobel prize in Chemistry for Thomas Cech’s discovery of Ribozymes) and steroid hormone modulation of gene expression (in support of research into Protein Phosphorylation as a regulatory mechanism of proteins leading to the 1992 Nobel prize for Edmund Fisher and Edwin Krebs and leading to the discovery of COX-2 enzyme and COX-2 inhibitors in 1991 which was subsequently “borrowed” by Pfizer and made into the blockbuster drug Celebrex, reaffirming Dr Young’s assertion that I was leaving academia to go work in the “Evil Empire” that is Industrial research).

But enough name dropping, lest you think this blog is just about shameless self-promotion.

Back to the story. We moved down here in 1988 to work in the Molecular Diagnostics Division of Life Technologies. This was sold in 1990 or ‘91 to become Digene. To the left you see the 25 year old version of yours truly, pretending I am doing lab work. This is from the front page of the Baltimore Sun’s Business section on Dec. 21, 1988. The story was about our pending FDA approval for (one of?) the first clinically approved DNA test on the market. You may notice that the paper has a tinge of orange from age, and if you look closely, you’ll see my beard was still orange, too. By the way, the Dow closed at a mere 2,166 that day, a 1-year CD would yield 9.00 % and the Prime was 10.5%.

Updates from Ft Detrick

It’s Sunday morning, watching Meet the Press, so I guess it is a good time to update a few things going on at the Fort.

First, I will make a disclosure that much of my information is coming through my affiliation with the Frederick Chapter of AFCEA International. I have blogged this before, but wanted you to take a look at the updated and improved web site. Of particular note is the AFCEA Golf Outing at Whiskey Creek May 13th. Since we all like to golf and MdBio is no longer sponsoring their tournament in Frederick (which was always one of the best BioTech social events of the year IMHO), we’re going to try ad carry on the tradition. There are still sponsorships available and you can bet I’ll be harassing my friends at MedImmune, Lonza and other big Bio’s to get involved.

The presentation last month was by David W. Williams, US Army Medical Research & Material Command. You can get a copy of his presentation HERE. The USAMRMC and Mr Williams command a huge purchasing budget for all things related to Medical Materials and Medical-directed Research. The emphasis of this presentation were updates regarding the construction of the consolidated Logistics facility, the Defense Medical Logistics Center.

Also at the Fort this month, I wanted to highlight the excellent Seminar series, which is open to the public. I put the whole schedule on the Calendar page. A couple of highlights (for me) are
Dr. Valeri Vasioukhin, PhD, Cell Polarity in Self-Renewal and Differentiation of Stem/Progenitor Cells on April 7th and on April 18th Stem Cells and Early Lineage Development given by Janet Rossant, PhD. from the Hospital for Sick Children of Toronto.

There is also a very interesting looking retreat to Gettysburg on April 10th & 11th called the Cancer And Inflammation Program Workshop. Looks like a very comprehensive and interesting agenda, but not sure if I’ll be able to sneak out for two days.

Frederick Team Synthesizes Cyclostreptin Analogue

Here’s one for you, if you like all of the nitty gritty science stuff.  I wish NCI or Ft Detrick had a site that would just tell us everything that has been published recently, don’t you?

ASAP Article, 10.1021/np800056m
Web Release Date: February 26,
2008 Copyright © 2008 American Chemical Society and American Society of Pharmacognosy
Interaction of a Cyclostreptin Analogue with the Microtubule Taxoid Site: The Covalent Reaction Rapidly Follows Binding^⊥

Ruoli Bai,^† Christopher D. Vanderwal,^‡ J. Fernando Díaz,^§ and Ernest Hamel^*†

Toxicology and Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland 21702, Department of Chemistry, University of California at Irvine, Irvine, California 92697, and Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid 28040, Spain

Received October 1, 2007

Abstract:

The natural product cyclostreptin reacts covalently and stoichiometrically with microtubules, at either of two amino acid residues of β-tubulin, Thr-218 or Asn-226, but much less extensively and only at Thr-218 in unpolymerized tubulin. It was found that 8-acetylcyclostreptin (8AcCS) induces tubulin assembly in a manner almost identical with that of cyclostreptin. We therefore synthesized [¹⁴C-acetyl]8AcCS and studied the kinetics of its interaction with glutaraldehyde-stabilized microtubules and with unassembled tubulin. With the microtubules, we found that 8AcCS bound rapidly, with a minimal (unmeasurable with the radiolabeled analogue) lag prior to the occurrence of the covalent reaction. Apparent reaction rate constants for the overall reaction ranged from 6.2 × 10² M⁻¹ s⁻¹ at 0 °C to 5.6 × 10³ M⁻¹ s⁻¹ at 20 °C. The rate constants obtained at 0 and 10 °C indicate an activation energy for the reaction of about 27 kcal/mol, while those obtained at 10 and 20 °C indicate an activation energy of about 7.7 kcal/mol. With the unpolymerized tubulin, we did find a minimal covalent reaction occurred without apparent microtubule assembly, but a substantial reaction only occurred following assembly. In conclusion, the radiolabeled 8AcCS shows that an extensive covalent interaction of ligand with tubulin requires microtubule assembly and that the covalent reaction occurs rapidly after the initial binding interaction.

Download the full text: PDF | HTML

Frederick Team Discovers new Breast Cancer Marker

This news just flashed across the wire, from the Sloan-Kettering Cancer Institute site:

Researchers Identify New Genetic Marker for Breast Cancer

March 3, 2008

NEW YORK, NY - An international group of investigators led by scientists at Memorial Sloan-Kettering Cancer Center (MSKCC) and the National Cancer Institute has identified a new genetic marker of risk for breast cancer. Women with this DNA variation are at a 1.4 times greater risk of developing breast cancer compared to those without the variation. The findings are to be published online on March 3, 2008 in the journal Proceedings of the National Academy of Sciences.

“These results are exciting because they point us to new molecular pathways that may be associated with breast cancer,” said the head of the research team and the study’s senior author, Kenneth Offit, MD, MPH, Chief of the Clinical Genetics Service at MSKCC.

The study used a methodology called genome-wide association mapping, which looks at genetic variations across the entire genome that alter the individual building blocks of DNA makeup. These alterations may occur more frequently in individuals who have certain types of disease than in carriers without such disease. In this study, a new gene locus, a specific place on a chromosome where a gene is located, was associated with breast cancer risk. That gene locus is on the long arm of chromosome 6.

“These research findings are of great interest because of the method of genome- wide association used to discover this new locus as well as others in recent months,” said Bert Gold, PhD, a Staff Scientist at the National Cancer Institute in Frederick, MD., and first author of the current study.

While the risk associated with this genetic marker is much lower than that of BRCA genetic mutations for example, this discovery will increase the understanding of the genetic variants that contribute to breast cancer.

“These results are exciting because they point us to new molecular pathways that may be associated with breast cancer.” – Kenneth Offit, MD, MPH, study’s senior author and Chief of the Clinical Genetics Service at MSKCC

Researchers used samples largely from MSKCC, but also from other sites in the US, Canada, and Israel. Participants were all of Ashkenazi (Eastern European Jewish) ancestry. The study used a three-phase design centered on 249 families with multiple cases of breast cancer and no mutations of the BRCA genes.

“This newly identified genetic marker will not have any immediate clinical implications or impact on current screening guidelines for familial breast cancer,” said Dr. Offit. “As such, a test for these markers is not available to the general public and these tests should be performed only as part of research studies.”

Dr. Offit’s research team is now confirming that this risk marker is observed in other populations, and is studying possible changes in two genes in the chromosome 6q region.

The study was funded in part by federal funds from the Intramural Research Program of the National Cancer Institute, Center for Cancer Research, the Breast Cancer Research Foundation, the Susan Komen Foundation, the Lymphoma Foundation, and the Niehaus, Southworth, Weissenbach Cancer Research Fund.

Good Stuff from NCI

I ran across an article the other day on the NIH web site about a break through discovery made by a group in Frederick.

Just a cut and paste from the NIH web site:

Scientists Find Antibody that Can Potently Neutralize Two VirusesIn laboratory experiments, scientists at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), and their colleagues supported by the NIH National Institute of Allergy and Infectious Disease (NIAID), have discovered an antibody that neutralizes two viruses classified as henipaviruses. Nipah virus (NiV) and Hendra virus (HeV) are highly infectious agents that transitioned from infecting flying foxes in the mid-1990s to causing fatal disease in humans and livestock in Australia, Bangladesh, India, Malaysia, and Singapore. Recent outbreaks have resulted in encephalitis and acute respiratory distress, person-to-person transmission, and up to 70 percent fatality rates. The finding appears in the Feb. 15, 2008, issue of The Journal of Infectious Diseases.

Antibodies are proteins that are found in blood or other bodily fluids of vertebrates and are used by the immune system to identify and neutralize foreign molecules, including bacteria and viruses. According to study author Dimiter S. Dimitrov, Ph.D., of NCI’s Center for Cancer Research in Frederick, Md., “We hope that with further research this antibody can save human lives. The insights offered about how it works also could potentially provide a starting point for the development of tools for targeting other diseases.”

The first step in countering infections caused by these viruses is to find antibodies that can neutralize them. Viral neutralization is the process by which an antibody alone or an antibody plus another molecule, called complement, block the infectivity of a virus. Zhongui Zhu, Ph.D., of Dimitrov’s group and their NIAID-supported collaborator Christopher Broder, Ph.D., of the Uniformed Services University of the Health Sciences, Bethesda, Md., had previously identified antibodies to NiV and HeV by panning a large antibody library against a soluble form of the protein that makes up the HeV shell. One of these antibodies, m102, exhibited a strong ability to neutralize both NiV and HeV.

In their current experiment, the researchers created an improved version of m102, called m102.4, by using a complex procedure called in vitro maturation. The m102.4 version is even more potent than its parent antibody, m102, and can neutralize both HeV and NiV without a loss of cross-reactivity, which is the ability of an antibody that is specific for one target, or antigen, to bind to a second antigen. The researchers believe that the m102.4 clone is the first fully human antibody that is capable of potently neutralizing both HeV and NiV. Their results suggest that m102.4 may prove useful as a therapeutic for treatment of diseases caused by henipaviruses. Their initial experiments in small mammals called ferrets found that m102.4 was well tolerated, exhibited no adverse effects, and retained high neutralizing activity, which may point to this antibody’s potential for clinical use as a preventive agent, a diagnostic probe, or an antiviral therapeutic.

“The generation of a potent antibody against both HeV and NiV could help control outbreaks in geographical regions susceptible to henipaviruses, and result in a benefit for mankind,” said Dimitrov. He also noted that the laboratory technology they used for the maturation of antibodies is being used for the development of antibodies against cancer.

This study was a collaboration with investigators Katharine N. Bossart, Ph.D., and Lin-Fa Wang, Ph.D., from Geelong, Victoria, Australia, where there is a high-level safety and security facility for testing the antibody.

For more information on Dimitrov’s laboratory at CCR Frederick, please go to http://ccr.cancer.gov/staff/staff.asp?profileid=5749.

For more information about cancer, please visit the NCI Web site at http://www.cancer.gov, or call NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

NIAID is a component of the National Institutes of Health. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on basic immunology, transplantation and immune-related

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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Reference:
Zhu Z, Bossart K, Bishop KA, Grameri G, Dimitrov AS, McEachern JA, Feng Y, Middleton D, Wang L, Broder CC, Dimitrov DS. Exceptionally Potent Cross-Reactive Neutralization of Nipah and Hendra Viruses by a Human Monoclonal Antibody. The Journal of Infectious Diseases, February 15, 2008.

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The Journal of Visualized Experimention

I added a new link into my “SOPs and Protocols” page linking to the JoVE web site.  As blogged many times over at PIMM, JoVE is a really neat site chock full of video protocols, from the basics like Western Blotting to ones involving Immunohistochemistry of human neural stem cells.

Y’all need to check it out

More Tales About Cats and Virus

I picked up another story from the same group at NCI/SAIC-Frederick from GenomeWeb Daily News feed.

It would appear that if you have any questions about the feline genome, then Dr SJ O’Brien would be the person to speak with. I have always found it interesting, and quite different than myself, that people can get so deep and specific about a topic such as the cat genome. And this morning I have festered away quite a few hours on the topic myself. I find it fascinating that the authors are able to draw analogies between African Lion FIV and modes of transmission of HIV in humans.

The most recent article is actually available on from an “Open Access”, peer-reviewed journal, BMC Genomics. So, here’s the skinny on this publication (or should I say, just scratching the surface):

Conclusions

This study demonstrates the necessity of whole-genome analysis to complement population/gene-based studies, which are of limited utility in uncovering complex events such as recombination that may lead to functional differences in virulence and pathogenicity. These full-length lion lentiviruses are integral to the advancement of comparative genomics of human pathogens, as well as emerging disease in wild populations of endangered species.

Interestingly, in another featured article in the same publication, yet another “Frederick Connection”. One of the authors of the paper “A large-scale proteomic analysis of human embryonic stem cells“, Mahendra S Rao, was working closely with SuperArray on their Stem Cell platforms and then left to go to work across the street at Invitrogen.  I think that’s pretty cool!

Hopkins: A Hole to Throw Our Money into

I guess this should be a good thing for all of us, but let me rant a bit. Hopkins is consuming $1.3 BILLION DOLLARS of our tax money annually, grants we could be getting and converting into goods and services, and producing a meager $12.5 MILLION from 799 licenses for technology. Anyone who goes into business looking for that kind of return on their investment needs to have the head examined. Granted, a good amount of their research does go into medical research for which we can not quantify their efforts to relieve human disease and suffering. But still, I think we deserve more with our tax money.
Here’s the article from this weeks Gazette:

Johns Hopkins tops in R&D spending

Johns Hopkins University of Baltimore conducted $1.49 billion in science, medical and engineering research in fiscal 2006, making it the top U.S. academic institution in total research and development spending for the 28th year in a row, according to a new National Science Foundation ranking.

The university also again ranked first on the foundation’s separate list of federally funded research and development, spending $1.3 billion in fiscal 2006 on research supported by such agencies as the National Institutes of Health, NASA and the Department of Defense.

“Johns Hopkins is putting renewed emphasis on getting the results of our faculty’s research out into the marketplace where it can do the most good for patients and consumers,“ said Aris Melissaratos, who oversees technology transfer as senior adviser to the president for enterprise development at Johns Hopkins.

“In fiscal 2006, the university earned $12.5 million from 799 licenses and patents,“ Melissaratos said in a statement. “That’s a good performance, and we’re working hard to do an even better job of creating connections between our researchers and business.“

I have had the pleasure of meeting Aris Melissaratos and working with some of the programs he created while at DBED under Gov. Ehrlich. I hope his appointment at Hopkins is and indication that they see the error of their ways and are working to correct the problem.