The Lasker Foundation awarded Carnegie's Joseph G. Gall the prestigious 2006 Lasker Award for Special Achievement in Medical Science. The citation recognizes that Gall is "a founder of modern cell biology who has made seminal contributions to the field of chromosome structure and function, who invented in situ hybridization, and who has been a long-standing champion of women in science."
Gall has been staff scientist at the Carnegie Institution's Department of Embryology and adjunct professor of The Johns Hopkins University since 1983, and a Professor of Developmental Genetics of the American Cancer Society since 1984. His in situ hybridization technique, developed with graduate students Mary Lou Pardue and Susan Gerbi in 1969, is a powerful method that allows researchers to locate and map genes and specific sequences of DNA on a chromosome. It revolutionized molecular biology and is now used worldwide in gene studies.
"Joe Gall's achievements are a realization of Andrew Carnegie's original dream," remarked Carnegie president Richard Meserve. "Carnegie believed that if exceptional individuals are set free to work in an environment without constraints extraordinary discoveries will result."
Education and Career Path
As a teenager, Gall spent summers on a farm in northern Virginia, where his interest in the natural world flourished. "After much urging, my parents bought me a microscope when I was 14 years old--not one of the toys I had struggled with up to that time, but the real thing," he reflected. Without a local high school to attend, Gall was sent to a boarding school near Charlottesville, Virginia, where after three years the headmaster thought he was ready to go to college.
"How Yale was chosen I am not sure, but I arrived in New Haven in June 1945, just as the Second World War was coming to a close."
Gall received his B.S. from Yale University in zoology in 1949 and his Ph.D. from Yale in 1952. Between 1952 and 1964, he taught at the University of Minnesota in Minneapolis, where he became Professor of Zoology. In 1963 he returned to Yale as part of his sabbatical, but before his year was over he was offered a position as Professor of Molecular Biophysics and Biochemistry. In an unusual twist to an academic career, he decided to leave Yale in 1983 to join Carnegie's Department of Embryology so he could conduct research full time.
Research
Gall's career-long interest is how the structure of the cell, particularly the nucleus, is related to the synthesis and processing of ribonucleic acid, RNA, during gene activity. He specifically looks at changes in the chromosomes and other nuclear components when RNA is synthesized, processed, and transported from the cell's nucleus to the cytoplasm. The in situ hybridization technique takes advantage of the feature that DNA and RNA bond to each other via their complementary sequences. Gall and colleagues developed their technique of labeling RNA with a radioactive label and placing it on cells on a microscope slide. The RNA hybridizes, or binds, with its complement on the DNA and is detected by its radioactivity. This technique allows researchers to see where genes are and determine whether a gene has been turned on in developing embryos. The advent of fluorescent tags have increased the sensitivity and precision.
Gall's development of in situ hybridization was a byproduct of his renowned research on the so-called lampbrush chromosomes--the largest chromosomes in any animal. They reside in amphibian eggs and were named when first viewed in the nineteenth century because they look like brushes then used to clean the narrow chimneys of lamps. Gall looks at the unlaid eggs from the frog Xenopus, which are up to 1.5 millimeters (mm) in diameter, with a nucleus, or germinal vesicle (GV), that is 0.4 mm in diameter. Their large size makes them ideal for understanding chromosome structure and function, Gall's research area since the 1940s. Gall made many discoveries about genes in the lampbrush chromosome including gene amplification in which extra copies of DNA are created at certain times in the oocyte. Similar extra copies of genes are often seen in cancer cells.
Current Interests
Gall has worked with various organisms over the years, from frogs to the fruit fly. It has generally been thought that various factors involved in RNA synthesis travel separately to active genes on the chromosomes for processing.
Using Xenopus eggs, Gall now studies this process. By watching fluorescently tagged molecules, he is able to determine where these factors move. This tracking has led Gall and others to propose that the processing machinery is assembled in structures in the GV, called Cajal bodies, named for the man who described them 100 years ago, Spanish neurobiologist and Nobel laureate Ramуn y Cajal.
Allan Spradling, department director of Carnegie's Department of Embryology commented on Gall's influence: "Joe Gall stands out especially because of the way he has done cutting-edge science throughout a long career. A true scholar of biology, he repeatedly turns his deep knowledge of diverse biological systems and of the forgotten lore of science history into novel experimental approaches that have sometimes spawned whole new fields of study. He shares his unmatched knowledge of microscopy in a unique course combining mathematically rigorous optics with a hands-on examination of historic instruments from every major phase of the field's development. All of these activities are carried out with the highest standards of integrity, respect for others, genuine modesty and with a sheer joy at the pleasures of discovery that seems undiminished from the days when he roamed the Virginia fields with his butterfly net and microscope. In short, Joe Gall's approach to science has long been an inspiration to others and I feel fortunate to count myself among those who have benefited enormously from his example."
Honors and Awards
The Lasker Awards, considered the U.S. Nobels, recognize basic researchers and clinical scientists whose work has been seminal to understanding and treating disease. Since 1962, 71 Lasker Award recipients have gone on to win a Nobel Prize. The Special Achievement Award was created in 1994.
Joe Gall has received numerous other awards over the years for his scientific research, among them the 2004 Society for Developmental Biology Lifetime Achievement Award and the 1996 American Association for the Advancement of Science Mentor Award for Lifetime Achievement. He also received the E. B. Wilson Medal from the American Society for Cell Biology in 1993 and the Wilbur Cross Medal from Yale University in 1988. Gall is a member of the American Academy of Arts and Sciences (1968), the National Academy of Sciences (1972), the American Philosophical Society (1989).
Carnegie geneticists Barbara McClintock and Alfred Hershey, both Nobel laureates, also won Lasker awards for their seminal research.
Andrew Carnegie founded the Carnegie Institution in 1902 as an organization for scientific discovery. The Department of Embryology, founded in 1913 in affiliation with the Anatomy Department of Johns Hopkins University, is one of six departments within the institution. Carnegie scientists are leaders in plant biology, developmental biology, astronomy, materials science, global ecology, and Earth and planetary science.
Contact:
Carnegie Institution
четверг, 26 мая 2011 г.
Student Recognized For Investigations Into The Potential Use Of Bacteriophage Coatings For The Prevention Of Microbial Colonisation On Medical Devices
Oxoid, a world-leading microbiology brand, is pleased to award the Oxoid Prize for the Best Project in Microbiology (2008) at the University of Brighton School of Pharmacy and Biomolecular Sciences to Niamh Kilbride for her investigations into the potential use of bacteriophage coatings for the prevention of microbial colonisation on medical devices.
In her research project, Niamh investigated several different methods for the immobilisation of phage K, with a view to developing a coating that would be effective against Staphylococcus aureus NCTC 10788. She studied the retention of the bacteriophage when dried onto the surface of untreated and silanised glass. She then incorporated the bacteriophage into a hydrogel coating and investigated whether the coating was effective at preventing or inhibiting the growth of bacteria on its surface.
Niamh concluded that it is possible to create a bacteriophage coating that can prevent microbial colonisation at sufficiently high concentrations of bacteriophage. She also concluded that the development of a suitable bacteriophage coating could potentially reduce and prevent the growth of bacteria in vivo.
Alison Smith, pharmaceutical microbiology manager, Oxoid, commented, "We are delighted to recognise this excellent research project. Pharmaceutical microbiologists worldwide are involved in the development and testing of new antimicrobials to fight hospital-acquired infections associated with indwelling medical devices, such as catheters. As a world-leading microbiology brand, we are keen to promote microbiologists like Niamh whose research may hold the answers for the prevention of such infections."
Niamh was presented with a framed certificate and a cheque for ВЈ150 prior to the graduation ceremonies at the University.
For further information about Oxoid products for clinical and industrial use, visit oxoid.
Oxoid is part of Thermo Fisher Scientific Inc., the world leader in serving science.
About Thermo Fisher Scientific
Thermo Fisher Scientific Inc. (NYSE: TMO) is the world leader in serving science, enabling our customers to make the world healthier, cleaner and safer. With annual revenues of $10 billion, we have more than 30,000 employees and serve over 350,000 customers within pharmaceutical and biotech companies, hospitals and clinical diagnostic labs, universities, research institutions and government agencies, as well as environmental and industrial process control settings. Serving customers through two premier brands, Thermo Scientific and Fisher Scientific, we help solve analytical challenges from routine testing to complex research and discovery. Thermo Scientific offers customers a complete range of high-end analytical instruments as well as laboratory equipment, software, services, consumables and reagents to enable integrated laboratory workflow solutions. Fisher Scientific provides a complete portfolio of laboratory equipment, chemicals, supplies and services used in healthcare, scientific research, safety and education. Together, we offer the most convenient purchasing options to customers and continuously advance our technologies to accelerate the pace of scientific discovery, enhance value for customers and fuel growth for shareholders and employees alike.
Thermo Fisher Scientific
In her research project, Niamh investigated several different methods for the immobilisation of phage K, with a view to developing a coating that would be effective against Staphylococcus aureus NCTC 10788. She studied the retention of the bacteriophage when dried onto the surface of untreated and silanised glass. She then incorporated the bacteriophage into a hydrogel coating and investigated whether the coating was effective at preventing or inhibiting the growth of bacteria on its surface.
Niamh concluded that it is possible to create a bacteriophage coating that can prevent microbial colonisation at sufficiently high concentrations of bacteriophage. She also concluded that the development of a suitable bacteriophage coating could potentially reduce and prevent the growth of bacteria in vivo.
Alison Smith, pharmaceutical microbiology manager, Oxoid, commented, "We are delighted to recognise this excellent research project. Pharmaceutical microbiologists worldwide are involved in the development and testing of new antimicrobials to fight hospital-acquired infections associated with indwelling medical devices, such as catheters. As a world-leading microbiology brand, we are keen to promote microbiologists like Niamh whose research may hold the answers for the prevention of such infections."
Niamh was presented with a framed certificate and a cheque for ВЈ150 prior to the graduation ceremonies at the University.
For further information about Oxoid products for clinical and industrial use, visit oxoid.
Oxoid is part of Thermo Fisher Scientific Inc., the world leader in serving science.
About Thermo Fisher Scientific
Thermo Fisher Scientific Inc. (NYSE: TMO) is the world leader in serving science, enabling our customers to make the world healthier, cleaner and safer. With annual revenues of $10 billion, we have more than 30,000 employees and serve over 350,000 customers within pharmaceutical and biotech companies, hospitals and clinical diagnostic labs, universities, research institutions and government agencies, as well as environmental and industrial process control settings. Serving customers through two premier brands, Thermo Scientific and Fisher Scientific, we help solve analytical challenges from routine testing to complex research and discovery. Thermo Scientific offers customers a complete range of high-end analytical instruments as well as laboratory equipment, software, services, consumables and reagents to enable integrated laboratory workflow solutions. Fisher Scientific provides a complete portfolio of laboratory equipment, chemicals, supplies and services used in healthcare, scientific research, safety and education. Together, we offer the most convenient purchasing options to customers and continuously advance our technologies to accelerate the pace of scientific discovery, enhance value for customers and fuel growth for shareholders and employees alike.
Thermo Fisher Scientific
Functional Amino Acids Regulate Key Metabolic Pathways
Functional amino acids play a critical role in the development of both animals and humans, according to a Texas AgriLife Research scientist.
In a journal article appearing in the American Society for Nutrition (Advances in Nutrition 1:31-37, 2010), Dr. Guoyao Wu, AgriLife Research animal nutritionist and senior faculty fellow in the department of animal science at Texas A&M University, calls for scientists to "think out of the box" and place more emphasis on this area of study.
"We need to move forward and capitalize on the potential of functional amino acids in improving health and animal production," he said.
A functional amino acid is an amino acid that can regulate key metabolic pathways to improve health, growth, development and reproduction of animals and humans, Wu said.
"This involves cell signaling through amino acids and their metabolites, and the metabolic pathways may include protein synthesis, antioxidative reactions and oxidation of energy substrates," he said. "A functional amino acid can be either a 'nonessential' or an 'essential' amino acid."
Past research emphasis has focused primarily on essential amino acids. However, Wu says both essential amino acids and non-essential amino acids should be taken into consideration.
"This is important when formulating balanced diets to maximize growth performance in livestock species, poultry and fish," he said. "It is also recommended that nonessential amino acids be provided to humans to prevent growth retardation and chronic diseases."
Wu's previous research discovered that arginine, an amino acid, contributes many positive benefits in growth and embryo development in pigs, sheep and rats. Arginine also aids in fighting obesity. Wu has identified this as an important area for expanded research on new amino acids and health.
"Currently in the U.S., more than 60 percent of adults are overweight or obese," he said. "Globally, more than 300 million adults are obese and more than 1 billion are overweight. Also, a large number of children in the U.S. and other countries are overweight or obese. The most urgent needs of new research in amino acids and health are the roles of functional amino acids in the treatment and prevention of obesity and its associated cardiovascular dysfunction."
Wu also said that dietary supplementation with arginine can help improve meat quality in pigs prior to slaughter.
The two top scientific discoveries in the field of amino acids and health over the past two decades are nitric oxide synthesis from arginine and the role of amino acids in cell signaling.
"An important area of research in the next few years may be to study the molecular and cellular mechanisms whereby some amino acids (e.g., arginine) can regulate metabolic pathways in animals and humans," he said. "An example is how arginine reduces obesity and ameliorates the metabolic syndrome, and how elevated levels of leucine may contribute to mitochondrial dysfunction and insulin resistance (including vascular resistance) in obese subjects."
He said "unquestionably" recent advances in understanding functional amino acids are "expanding our basic knowledge of protein metabolism and transforming practices of nutrition worldwide."
Though nutritional studies conducted on animals have benefited human health, Wu suggests that caution should be taken to "extrapolate animal data to humans" as dietary requirements differ from one species to another.
Wu said that humans need diets with balanced portions of amino acids for cardiovascular and reproductive health.
Source:
Dr. Guoyao Wu
Texas A&M AgriLife Communications
In a journal article appearing in the American Society for Nutrition (Advances in Nutrition 1:31-37, 2010), Dr. Guoyao Wu, AgriLife Research animal nutritionist and senior faculty fellow in the department of animal science at Texas A&M University, calls for scientists to "think out of the box" and place more emphasis on this area of study.
"We need to move forward and capitalize on the potential of functional amino acids in improving health and animal production," he said.
A functional amino acid is an amino acid that can regulate key metabolic pathways to improve health, growth, development and reproduction of animals and humans, Wu said.
"This involves cell signaling through amino acids and their metabolites, and the metabolic pathways may include protein synthesis, antioxidative reactions and oxidation of energy substrates," he said. "A functional amino acid can be either a 'nonessential' or an 'essential' amino acid."
Past research emphasis has focused primarily on essential amino acids. However, Wu says both essential amino acids and non-essential amino acids should be taken into consideration.
"This is important when formulating balanced diets to maximize growth performance in livestock species, poultry and fish," he said. "It is also recommended that nonessential amino acids be provided to humans to prevent growth retardation and chronic diseases."
Wu's previous research discovered that arginine, an amino acid, contributes many positive benefits in growth and embryo development in pigs, sheep and rats. Arginine also aids in fighting obesity. Wu has identified this as an important area for expanded research on new amino acids and health.
"Currently in the U.S., more than 60 percent of adults are overweight or obese," he said. "Globally, more than 300 million adults are obese and more than 1 billion are overweight. Also, a large number of children in the U.S. and other countries are overweight or obese. The most urgent needs of new research in amino acids and health are the roles of functional amino acids in the treatment and prevention of obesity and its associated cardiovascular dysfunction."
Wu also said that dietary supplementation with arginine can help improve meat quality in pigs prior to slaughter.
The two top scientific discoveries in the field of amino acids and health over the past two decades are nitric oxide synthesis from arginine and the role of amino acids in cell signaling.
"An important area of research in the next few years may be to study the molecular and cellular mechanisms whereby some amino acids (e.g., arginine) can regulate metabolic pathways in animals and humans," he said. "An example is how arginine reduces obesity and ameliorates the metabolic syndrome, and how elevated levels of leucine may contribute to mitochondrial dysfunction and insulin resistance (including vascular resistance) in obese subjects."
He said "unquestionably" recent advances in understanding functional amino acids are "expanding our basic knowledge of protein metabolism and transforming practices of nutrition worldwide."
Though nutritional studies conducted on animals have benefited human health, Wu suggests that caution should be taken to "extrapolate animal data to humans" as dietary requirements differ from one species to another.
Wu said that humans need diets with balanced portions of amino acids for cardiovascular and reproductive health.
Source:
Dr. Guoyao Wu
Texas A&M AgriLife Communications
Tweaking Taxol Points Way To A Greener, More Productive Future
As the effective cancer-treatment drug Taxol enters its next generation, Michigan State University announces discoveries which point to both environmentally friendly ways to produce more Taxol, and ultimately innovations to produce a more potent second-generation drug.
Kevin Walker, a chemistry and biochemistry and molecular biology assistant professor, in the March issue of Chemistry & Biology, reports a step toward manufacturing more-potent Taxol molecules that could potentially reduce treatment dosages. The methods described minimize dangerous chemical usage, and put E.coli to work in the production process.
"We're trying to develop a biosynthetic process for the drugs that circumvents the use of organic solvent-based methods requiring costly waste management," Walker said. "This attempt is a green chemistry approach to produce more potent versions of Taxol."
Taxol - generically known as paclitaxel - is a top-selling cancer-fighting drug. It's most commonly used against ovarian and breast cancers, but currently is used in certain aspects of heart disease treatment, and is showing promise in Alzheimer's therapy.
Taxol is derived in small quantities from the Pacific yew tree. To fulfill large-scale production, pharmaceutical companies isolate, from the tree, an abundant natural product that is synthetically converted to Taxol in the laboratory.
Now, as abundant molecules from the yew are being synthetically modified for new, more potent versions of Taxol, Walker, along with Catherine Loncaric, a visiting research associate, and undergraduate Erin Merriweather, is looking for alternative, biological routes to introduce the modifications. Walker's laboratory makes use of recently identified genes of the yew that produce enzymes that craft the pathway to Taxol. The targets: five enzymes that biosynthetically decorate the core of the Taxol molecule.
The enzymes in natural and, potentially, genetically modified form can be used to produce second-generation versions of the drug. Walker said the added advantage is that water-based chemicals rather than chlorinated solvents can be used with his methods.
For reasons ranging from competitive advantage to corporate culture, or to a desire to be a good corporate citizen, pharmaceutical companies are drawn to finding ways to minimize their environmental footprint as they make life-saving drugs.
"In fighting one pathological system, it makes sense to not create another problem that can have a global effect," Walker said.
Plus, Walker said assessing the Taxol pathway enzymes opens doors to new, more natural ways to make Taxol. He said that learning to genetically modify the qualities of the Pacific yew organism to make tomorrow's versions of Taxol could mean transferring all the genes - the entire pathway - into a bacterium for large-scale production of the new and improved Taxol, without further depleting the yew plant.
"Eventually, it will be cool when we're able potentially to have bacteria make all of the necessary plant enzymes, and we can sit back and watch E. coli make first- and second-generation Taxol molecules," Walker said.
The research was funded by MSU College of Natural Science. Walker's laboratory also is funded by the Michigan Agricultural Experiment Station.
Contact: Kevin Walker
walke284msu
Sue Nichols
University Relations
nicholsmsu
Michigan State University
View drug information on Taxol.
Kevin Walker, a chemistry and biochemistry and molecular biology assistant professor, in the March issue of Chemistry & Biology, reports a step toward manufacturing more-potent Taxol molecules that could potentially reduce treatment dosages. The methods described minimize dangerous chemical usage, and put E.coli to work in the production process.
"We're trying to develop a biosynthetic process for the drugs that circumvents the use of organic solvent-based methods requiring costly waste management," Walker said. "This attempt is a green chemistry approach to produce more potent versions of Taxol."
Taxol - generically known as paclitaxel - is a top-selling cancer-fighting drug. It's most commonly used against ovarian and breast cancers, but currently is used in certain aspects of heart disease treatment, and is showing promise in Alzheimer's therapy.
Taxol is derived in small quantities from the Pacific yew tree. To fulfill large-scale production, pharmaceutical companies isolate, from the tree, an abundant natural product that is synthetically converted to Taxol in the laboratory.
Now, as abundant molecules from the yew are being synthetically modified for new, more potent versions of Taxol, Walker, along with Catherine Loncaric, a visiting research associate, and undergraduate Erin Merriweather, is looking for alternative, biological routes to introduce the modifications. Walker's laboratory makes use of recently identified genes of the yew that produce enzymes that craft the pathway to Taxol. The targets: five enzymes that biosynthetically decorate the core of the Taxol molecule.
The enzymes in natural and, potentially, genetically modified form can be used to produce second-generation versions of the drug. Walker said the added advantage is that water-based chemicals rather than chlorinated solvents can be used with his methods.
For reasons ranging from competitive advantage to corporate culture, or to a desire to be a good corporate citizen, pharmaceutical companies are drawn to finding ways to minimize their environmental footprint as they make life-saving drugs.
"In fighting one pathological system, it makes sense to not create another problem that can have a global effect," Walker said.
Plus, Walker said assessing the Taxol pathway enzymes opens doors to new, more natural ways to make Taxol. He said that learning to genetically modify the qualities of the Pacific yew organism to make tomorrow's versions of Taxol could mean transferring all the genes - the entire pathway - into a bacterium for large-scale production of the new and improved Taxol, without further depleting the yew plant.
"Eventually, it will be cool when we're able potentially to have bacteria make all of the necessary plant enzymes, and we can sit back and watch E. coli make first- and second-generation Taxol molecules," Walker said.
The research was funded by MSU College of Natural Science. Walker's laboratory also is funded by the Michigan Agricultural Experiment Station.
Contact: Kevin Walker
walke284msu
Sue Nichols
University Relations
nicholsmsu
Michigan State University
View drug information on Taxol.
Gene Fusion Subtypes In Prostate Carcinoma Have Clinical Implications
Building on an earlier study
that used Oncomine(TM) to identify ETS-fusion proteins in prostate cancer
(Science, Oct 28 2005), Tomlins et al. today report the identification of
four additional classes of ETS rearrangements in prostate cancer, each of
which activates ETV1 by a different genetic mechanism (Nature, Aug 2 2007).
Tomlins et al. queried the Oncomine database to determine the tissue
specificity of three of the new fusion gene partners, demonstrating that
two new partners are prostate cancer specific while the third partner is a
generally over-expressed 'house-keeping' gene. In addition, Oncomine
Concepts Map was applied to test for similarities between the set of genes
regulated by ETV1 with sets of genes related to other biological concepts.
This analysis revealed a clear association between ETV1 activation and
cellular invasion, a hallmark of cancer.
Oncomine, a dynamic repository that combines rich data, sophisticated
analysis, and responsive user interface, empowers oncology research by
bringing data analysis tools to a large cancer gene expression database,
which includes data from 20,000+ microarray experiments curated from 300+
independent studies. Oncomine Concepts Map, an extension of Oncomine, is a
compilation of nearly 8,000 Oncomine cancer gene signatures together with
11,500 gene, protein, drug, and pathway signatures collected from the
literature and other public sources.
"This study marks an important advance in our understanding of the
molecular basis of prostate cancer. Oncomine again proved invaluable in
examining the expression of genes in cancer, and in this case aided in the
characterization of new sub-types of prostate cancer," said Dan Rhodes,
Ph.D., co-founder and Chief Science Officer of Compendia Bioscience. "The
authors went on to show that one of the new subtypes is unlikely to respond
to conventional anti-androgen therapy, and another may be adversely
affected by standard therapies. This strongly suggests that using this type
of molecular information to distinguish patient populations will have
important clinical implications."
About Compendia Bioscience, Inc.
Compendia Bioscience is dedicated to harnessing the global collection
of high throughput molecular data to provide researchers with the data and
analysis tools necessary to validate biomarker and gene target discoveries,
better understand mechanisms of disease, and optimize clinical outcomes.
About Oncomine(TM)
Oncomine(TM) combines a rapidly growing compendium of 20,000+ cancer
transcriptome profiles with a sophisticated analysis engine and a powerful
web application for data mining and visualization. Oncomine facilitates
rapid and reliable biomarker and therapeutic target discovery, validation,
and prioritization.
About Oncomine(TM) Concepts Map
Oncomine Concepts Map is licensed to commercial users as part of the
Oncomine Concepts Edition and the Oncomine Enterprise Edition. Visit
compendiabio for more information. An academic preview
edition is available to academic and non-profit researchers at
oncomine.
Compendia Bioscience, Inc.
compendiabio
that used Oncomine(TM) to identify ETS-fusion proteins in prostate cancer
(Science, Oct 28 2005), Tomlins et al. today report the identification of
four additional classes of ETS rearrangements in prostate cancer, each of
which activates ETV1 by a different genetic mechanism (Nature, Aug 2 2007).
Tomlins et al. queried the Oncomine database to determine the tissue
specificity of three of the new fusion gene partners, demonstrating that
two new partners are prostate cancer specific while the third partner is a
generally over-expressed 'house-keeping' gene. In addition, Oncomine
Concepts Map was applied to test for similarities between the set of genes
regulated by ETV1 with sets of genes related to other biological concepts.
This analysis revealed a clear association between ETV1 activation and
cellular invasion, a hallmark of cancer.
Oncomine, a dynamic repository that combines rich data, sophisticated
analysis, and responsive user interface, empowers oncology research by
bringing data analysis tools to a large cancer gene expression database,
which includes data from 20,000+ microarray experiments curated from 300+
independent studies. Oncomine Concepts Map, an extension of Oncomine, is a
compilation of nearly 8,000 Oncomine cancer gene signatures together with
11,500 gene, protein, drug, and pathway signatures collected from the
literature and other public sources.
"This study marks an important advance in our understanding of the
molecular basis of prostate cancer. Oncomine again proved invaluable in
examining the expression of genes in cancer, and in this case aided in the
characterization of new sub-types of prostate cancer," said Dan Rhodes,
Ph.D., co-founder and Chief Science Officer of Compendia Bioscience. "The
authors went on to show that one of the new subtypes is unlikely to respond
to conventional anti-androgen therapy, and another may be adversely
affected by standard therapies. This strongly suggests that using this type
of molecular information to distinguish patient populations will have
important clinical implications."
About Compendia Bioscience, Inc.
Compendia Bioscience is dedicated to harnessing the global collection
of high throughput molecular data to provide researchers with the data and
analysis tools necessary to validate biomarker and gene target discoveries,
better understand mechanisms of disease, and optimize clinical outcomes.
About Oncomine(TM)
Oncomine(TM) combines a rapidly growing compendium of 20,000+ cancer
transcriptome profiles with a sophisticated analysis engine and a powerful
web application for data mining and visualization. Oncomine facilitates
rapid and reliable biomarker and therapeutic target discovery, validation,
and prioritization.
About Oncomine(TM) Concepts Map
Oncomine Concepts Map is licensed to commercial users as part of the
Oncomine Concepts Edition and the Oncomine Enterprise Edition. Visit
compendiabio for more information. An academic preview
edition is available to academic and non-profit researchers at
oncomine.
Compendia Bioscience, Inc.
compendiabio
Seizure Generation In Brain Is Isolated From Surrounding Brain Regions
Mayo Clinic researchers found that the part of the brain generating seizures in individuals with epilepsy is functionally isolated from surrounding brain regions. The researchers hope this finding could be a clinical biomarker to help identify individuals with abnormal brain function. This study was presented at the American Epilepsy Society's annual meeting in San Antonio on Dec. 4.
Epilepsy is a disorder characterized by the occurrence of two or more seizures. It affects almost 3 million Americans.
"The synchronization of local and distributed neuronal assemblies underlies fundamental brain processes like perception, learning and cognition," says Gregory Worrell, M.D., Ph.D., a Mayo Clinic epileptologist and an author of this study. "In neurological disease, neuronal synchrony can be altered, and in epilepsy the synchrony plays an important role in the generation of seizures."
Mayo Clinic researchers investigated neuronal synchrony by studying intracranial EEG (electroencephalogram) recordings from patients with epilepsy and control subjects with facial pain. Researchers discovered that the control patients had greater average synchrony than patients with focal epilepsy (when seizures are produced in a small part of the brain, not the entire brain). When implanted electrode pairs bridged seizure-generating brain and other brain regions, the synchrony was significantly less than between other electrode pairs in the epileptic brain and the control brain. The team also found that with greater activity in the seizure-generating region, there was less synchrony with neighboring tissue outside that region.
"Our study shows us that the part of the brain generating seizures is isolated from the surrounding brain regions," says Dr. Worrell. "This finding could serve as a clinical biomarker of an abnormal brain, and it can also be useful in epilepsy surgery and brain stimulation treatments, as well as helping us understand how seizures are generated."
Other scientists involved in this research include C. Warren, Ph.D.; S. Hu; S. Stead, M.D., Ph.D.; B. Brinkmann, and M. Bower, Ph.D.
Source: Mayo Clinic
Epilepsy is a disorder characterized by the occurrence of two or more seizures. It affects almost 3 million Americans.
"The synchronization of local and distributed neuronal assemblies underlies fundamental brain processes like perception, learning and cognition," says Gregory Worrell, M.D., Ph.D., a Mayo Clinic epileptologist and an author of this study. "In neurological disease, neuronal synchrony can be altered, and in epilepsy the synchrony plays an important role in the generation of seizures."
Mayo Clinic researchers investigated neuronal synchrony by studying intracranial EEG (electroencephalogram) recordings from patients with epilepsy and control subjects with facial pain. Researchers discovered that the control patients had greater average synchrony than patients with focal epilepsy (when seizures are produced in a small part of the brain, not the entire brain). When implanted electrode pairs bridged seizure-generating brain and other brain regions, the synchrony was significantly less than between other electrode pairs in the epileptic brain and the control brain. The team also found that with greater activity in the seizure-generating region, there was less synchrony with neighboring tissue outside that region.
"Our study shows us that the part of the brain generating seizures is isolated from the surrounding brain regions," says Dr. Worrell. "This finding could serve as a clinical biomarker of an abnormal brain, and it can also be useful in epilepsy surgery and brain stimulation treatments, as well as helping us understand how seizures are generated."
Other scientists involved in this research include C. Warren, Ph.D.; S. Hu; S. Stead, M.D., Ph.D.; B. Brinkmann, and M. Bower, Ph.D.
Source: Mayo Clinic
Award Received By Boston Medical Center/Boston University School Of Medicine Researcher
M. Michael Wolfe, M.D., professor of medicine and research professor of physiology and biophysics at Boston University School of Medicine and chief of the Gastroenterology Section at Boston Medical Center, was awarded an Individual Biomedical Research Award by The Hartwell Foundation. Wolfe, considered a premier authority on the biology of GI regulatory peptides, will receive $300,000 direct cost over three years as a Hartwell Investigator for his project, "Peptide Replacement Therapy Using Transgenic Stem Cells Delivered to the Small Intestinal Mucosa".
Wolfe and his colleagues are developing a technique to redress hormone and enzyme deficiencies that cause diseases such as type 1 diabetes. The technique relies on engineering stem cells that produce the missing peptides and implanting them in the small intestine.
Because of their molecular size and susceptibility to degradation by stomach acid and digestive enzymes, insulin and other hormones must currently be administered by injection. The discomfort and inconvenience associated with injections often diminish patient compliance, particularly in children, which increases the risk of long-term complications. This concern is of particular importance for patients with type 1 diabetes, who often require multiple daily insulin injections to maintain stable blood sugar. Type I diabetes is one of the most common severe chronic diseases in children (1/300 in the US) and a major cause of end-stage renal disease, blindness, cardiovascular disease and premature death in the general population.
In a manuscript published in Science in 2000, Wolfe and his collaborators reported that intestinal K-cells of transgenic mice, which normally manufacture a hormone called GIP, could be engineered to express insulin and maintain normal blood glucose levels, even after pancreatic insulin-producing ("islet-beta") cells were destroyed. Employing the same genetic approach, Wolfe plans to transform stem cells that, like pancreatic islet-beta cells, will produce insulin in response to food ingestion. Using endoscopy, he plans to introduce transformed cells into the intestinal lining, where they will be programmed to become K-cells and produce insulin as well as GIP. The relocation of insulin production to the upper small intestine will "hide" it from the autoimmune response that destroys beta-cells in type 1 diabetes. Moreover, because K- and beta-cells are functionally similar, the K-cell appears to represent the ideal candidate for "hosting" the "foreign" insulin gene.
Wolfe is recognized as one of the world's leading authorities on GIP, and he initially cloned the GIP cDNA and ascertained its central role as principal mediator of the "enteroinsular axis". This axis functions as the hormonal connection between the intestine and pancreas following the ingestion of food. He established GIP as the likely mediator of the glycemic index and has theorized that low carbohydrate diets and gastric bypass surgery mediate their beneficial effects in part by suppressing GIP expression. He proved its importance in obesity by demonstrating functional receptors on adipocytes and by showing that GIP, like insulin, suppresses the breakdown of fat, which in essence results in an increase in fat storage.
"Boston University is delighted to have been invited by The Hartwell Foundation to participate in this year's competition and is deeply proud of Dr. Wolfe's selection for this exceptionally competitive Individual Biomedical Research Award," said Karen Antman, MD, dean of Boston University School of Medicine and provost of Boston University Medical Campus. "The award provides strategic funding for remarkably original research that combines genetic engineering, stem cell therapeutics, and gastroenterology, with exciting potential clinical implications. Private funding is vital to advancing such high-risk, high-gain work, and we are very grateful to The Hartwell Foundation for playing that role at BU."
Wolfe is highly regarded for his ability to translate his own research and others' observations into the clinical arena. He has been funded nearly continuously by the National Institutes of Health since the early 1980s and is one of only a very few American academicians with an invention that culminated with a drug currently on the market (Pepcid Complete®).
"The Hartwell Foundation is honored to provide financial support to Dr. Wolfe," said Foundation President Frederick Dombrose, Ph.D. "Participating institutions nominated exceptional individuals, making this year's competition for Investigator awards very tough."
Each year, The Hartwell Foundation announces its Top Ten Centers of Biomedical Research, inviting each center to hold an internal competition to nominate four candidates for a Hartwell Individual Biomedical Research Award. In August, Boston University was invited to participate as an extraordinary 11th institution and to submit two nominees for consideration.
The Hartwell Foundation seeks to inspire innovation and achievement by providing financial support to individual researchers in the United States for innovative and cutting-edge applied biomedical research that has the potential to benefit children. The general aim is to provide funds for early stage research projects that have not yet qualified for funding from traditional sources.
More information about The Hartwell Foundation is available on their web site, at thehartwellfoundation/.
Source: Michelle Roberts
Boston University
View drug information on Pepcid Complete.
Wolfe and his colleagues are developing a technique to redress hormone and enzyme deficiencies that cause diseases such as type 1 diabetes. The technique relies on engineering stem cells that produce the missing peptides and implanting them in the small intestine.
Because of their molecular size and susceptibility to degradation by stomach acid and digestive enzymes, insulin and other hormones must currently be administered by injection. The discomfort and inconvenience associated with injections often diminish patient compliance, particularly in children, which increases the risk of long-term complications. This concern is of particular importance for patients with type 1 diabetes, who often require multiple daily insulin injections to maintain stable blood sugar. Type I diabetes is one of the most common severe chronic diseases in children (1/300 in the US) and a major cause of end-stage renal disease, blindness, cardiovascular disease and premature death in the general population.
In a manuscript published in Science in 2000, Wolfe and his collaborators reported that intestinal K-cells of transgenic mice, which normally manufacture a hormone called GIP, could be engineered to express insulin and maintain normal blood glucose levels, even after pancreatic insulin-producing ("islet-beta") cells were destroyed. Employing the same genetic approach, Wolfe plans to transform stem cells that, like pancreatic islet-beta cells, will produce insulin in response to food ingestion. Using endoscopy, he plans to introduce transformed cells into the intestinal lining, where they will be programmed to become K-cells and produce insulin as well as GIP. The relocation of insulin production to the upper small intestine will "hide" it from the autoimmune response that destroys beta-cells in type 1 diabetes. Moreover, because K- and beta-cells are functionally similar, the K-cell appears to represent the ideal candidate for "hosting" the "foreign" insulin gene.
Wolfe is recognized as one of the world's leading authorities on GIP, and he initially cloned the GIP cDNA and ascertained its central role as principal mediator of the "enteroinsular axis". This axis functions as the hormonal connection between the intestine and pancreas following the ingestion of food. He established GIP as the likely mediator of the glycemic index and has theorized that low carbohydrate diets and gastric bypass surgery mediate their beneficial effects in part by suppressing GIP expression. He proved its importance in obesity by demonstrating functional receptors on adipocytes and by showing that GIP, like insulin, suppresses the breakdown of fat, which in essence results in an increase in fat storage.
"Boston University is delighted to have been invited by The Hartwell Foundation to participate in this year's competition and is deeply proud of Dr. Wolfe's selection for this exceptionally competitive Individual Biomedical Research Award," said Karen Antman, MD, dean of Boston University School of Medicine and provost of Boston University Medical Campus. "The award provides strategic funding for remarkably original research that combines genetic engineering, stem cell therapeutics, and gastroenterology, with exciting potential clinical implications. Private funding is vital to advancing such high-risk, high-gain work, and we are very grateful to The Hartwell Foundation for playing that role at BU."
Wolfe is highly regarded for his ability to translate his own research and others' observations into the clinical arena. He has been funded nearly continuously by the National Institutes of Health since the early 1980s and is one of only a very few American academicians with an invention that culminated with a drug currently on the market (Pepcid Complete®).
"The Hartwell Foundation is honored to provide financial support to Dr. Wolfe," said Foundation President Frederick Dombrose, Ph.D. "Participating institutions nominated exceptional individuals, making this year's competition for Investigator awards very tough."
Each year, The Hartwell Foundation announces its Top Ten Centers of Biomedical Research, inviting each center to hold an internal competition to nominate four candidates for a Hartwell Individual Biomedical Research Award. In August, Boston University was invited to participate as an extraordinary 11th institution and to submit two nominees for consideration.
The Hartwell Foundation seeks to inspire innovation and achievement by providing financial support to individual researchers in the United States for innovative and cutting-edge applied biomedical research that has the potential to benefit children. The general aim is to provide funds for early stage research projects that have not yet qualified for funding from traditional sources.
More information about The Hartwell Foundation is available on their web site, at thehartwellfoundation/.
Source: Michelle Roberts
Boston University
View drug information on Pepcid Complete.
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