Friday, December 5, 2008
Cutting The Cord To Determine Babies' Health Risk From Toxic Exposure
Now, in the first study of its kind, a team of researchers has completed a global assessment of newborns' umbilical cord blood to better understand the fetal health risks from smoking mothers. The research was led by Johns Hopkins University and included Rolf Halden, a researcher from the Biodesign Institute at Arizona State University.
"Cigarette smoking is a massive onslaught on human physiology," said Halden, who works in the institute's Center for Environmental Biotechnology. Cigarette smoke is known to contain more than 4,000 chemicals, potentially affecting the health of a newborn baby on multiple levels, including low birth weight, premature delivery and small size for gestational age. The exact cause of these health effects continues to be the subject of investigation.
"Unfortunately, maternal cigarette smoking puts babies at risk of adverse birth outcomes and increases susceptibility to other diseases later in life," said Halden.
The research team's goal was to provide the first assessment of proteins detectable in infant blood and to identify possible molecular predictors, or biomarkers, of fetal health risks.
The emergence of improved analytical tools allowed the researchers to address newborn health risks and explore the environmental effects of a well-known toxin in a level of detail not previously available. These tools include high-speed DNA sequencing, a powerful instrumental analysis called proteomic mass spectrometry to enhance the detection of proteins in complex samples, and bioinformatics, or the raw computing power to perform massive data crunching to tease out and identify biomarkers.
In doing so, the team described over 200 serum proteins contained in umbilical cord blood, the vital link between mother and developing baby that shares between the pair both essential nutrients as well as unwanted toxins absorbed by the mother.
"Modern tools in mass spectrometry and bioinformatics have enabled us to obtain a first view of proteins contained in fetal cord blood serum and to single out among these more than a dozen interesting ones whose concentrations change as a function of chemical exposure. These biomarkers of exposure and early effect are the gold of protein mining," said Halden, who is also an associate professor in the Ira A. Fulton School of Engineering.
Halden, who joined ASU's Biodesign Institute in 2008, initiated the study while at Hopkins along with lead author David R. Colquhoun, and colleagues Lynn R. Goldman, Frank R. Witter, Robert N. Cole, Marjan Gucek, Malini Mansharamani, and Benjamin J. Apelberg. The results were published in the early online edition of the journal Environmental Health Perspectives (http://www.ehponline.org).
To best obtain a snapshot of fetal proteins at birth, the study needed to obtain cord blood samples as soon as possible after newborn delivery. This required the coordinated efforts of multiple investigators and the resources of the large teaching hospital at Hopkins to recruit study subjects. Among the participants were many doctors and nurses to help with deliveries and obtain cord blood samples along with graduate students who were on call and had to rush out in the middle of the night to collect samples, transfer and process them, and analyze the data from the study population.
The group started with a large pool of more than 300 cord blood samples, and after adjusting for parameters such as the age of the mothers, narrowed down their focus to a dozen babies, half from non-smoking mothers and the other half from pregnant smokers.
"The study was a little bit challenging in that we went out on a fishing expedition," said Halden. "We wanted to look at everything at the same time, and the ability to tease out from the soup of proteins only those of interest was the chief technical challenge of this project."
The team looked for new proteins or proteins levels that may have changed between the smoking and non-smoking groups. After analyzing more than 200 proteins through mass spectrometry in smoke-exposed and control groups, they found small changes in the levels of some proteins, which represented biomarkers of cigarette smoke exposure.
"Of 17 proteins that were significantly up- or down-regulated in the cord blood of babies born to smoking mothers, 14 have previously been described to be related to smoking in either adults or in the fetus," said Lyne Goldman, a professor in the Department of Environmental Health Sciences at Johns Hopkins' School of Public Health.
The protein biomarkers have been linked to key metabolic pathways involved in regulating nutrients, oxygen and inflammation processes. After their analysis, the team also discovered some surprising results that illustrate the subtlety of using biomarkers as an approach to peer into the molecular makeup of human health. "There was not a single protein unique to either the smoking or non-smoking group," said Halden. "The remarkable finding is that there were no unique biomarkers."
Halden explains that only through the combined use of the new technologies was the research team able to tease out the small differences in the proteins levels between the two study groups.
Asked about the reliability of the biomarkers that the research team identified? Halden said, "The truth is that we don't know yet. We only took a first snapshot of the protein profile in baby blood right after birth. But does it change over time and will the differences we detected persist? We don't know."
The group hopes to use the same techniques to examine a wide range of environmental exposures and their effect on human health. "These findings confirm and underscore the serious metabolic alterations that are occurring in utero to children of smoking mothers, alterations that may increase risk for chronic disease over a lifetime," said Hopkins colleague Frank Witter. "We hope that this method will be sensitive enough to detect proteomic changes associated with environmental exposures as well."
The ultimate hope is that through the use of biomarkers identified by the team, it may become possible to detect effects of toxic exposures early on, before the onset of disease. "This may open opportunities to improve health outcomes by reducing the occurrence and severity of disease from environmental exposures, said Halden."
Thursday, October 16, 2008
Researchers working on cancer detection blood test
"Stopping cancer early is the best solution," Dr. Samir M. Hanash told about 270 people attending the Biosciences Leadership Symposium: Translational Medicine at the University of Arizona Monday. The event continues Tuesday.
"We're on a fast-track development of a blood-based cancer biomarker using proteomics," said Hanash, molecular diagnostics program head at the Fred Hutchinson Cancer Research Center in Seattle. "We are searching through thousands of proteins to see which one is a good marker for this or that type of cancer."
By using proteomics, the study of the structures and functions of proteins, cancers such as breast, lung, pancreatic and others can be detected a year before symptoms develop, Hanash said.
He is using specimens collected at early stages of tumor development - before the onset of symptoms - from a variety of institutions, clinical trials and studies to have a broad base of samples, he said.
"This could have a great impact on treating cancer, before it metastasizes," said Laurence Hurley, associate director of the UA BIO5 Institute. "The earlier you can treat the cancer the better."
Bioscience is also leading to new technologies in rapid pathogen detection and identification, said Linda S. Powers, the Thomas R. Brown Professor of Bioengineering at UA.
She uses intrinsic fluorescence optical signatures to find microbial contaminants in water, air, food, mail and other places. The microbes give off light when excited by light having higher energy.
The detection technology is real time and uses no sample contact or added chemical reagents, she said.
"We look for the toxin itself," she said. "We're capable of pulling it out of very large volumes."
A BioBadge, which can be worn around the neck like an identification card, "breathes" air into a chip that can be tested for bacteria, toxins and viruses, she said.
Mobile sensor technology provides quick and inexpensive tests for water supplies that can keep drinking water safe from contamination, she said.
One application was testing water wells to see if they were safe following Hurricane Katrina, she said
Monday, September 29, 2008
Nanotechnology Will Make Proteomics Experiments Lightning Fast

Proteomics researchers learn a tremendous amount about disease by measuring every single protein in a group of unhealthy cells, but they need a faster way to sort the molecules before analyzing them. Tiny spheres, made from silicon dioxide, could solve the problem.
"In order to study the proteome, we need to separate the individual proteins from one another for analysis," said Douglas Malkin, a doctoral student at the University of Arizona. "Our materials self-assemble to form crystals that can quickly isolate each protein out by their size or hydrophobicity."
He and his adviser, chemist Mary Wirth, pack the small spheres into capillary tubes that feed into a nanospray mass spectrometer. When they squirt a crude mixture of proteins through that little pipe, each of them will come out the other side at a different time. As they pop out the other end, the machine will measure them.
"We are doing liquid chromatography," said Malkin. "We're just doing it on the nanoscale."
Malkin presented his work today at the American Chemical Society meeting in Las Vegas. He said that the new tool could help scientists discover new biomarkers -- molecules that indicate whether someone has a disease like cancer or diabetes.
Once researchers have identified new signposts of an illness, they can make blood tests that doctors will use to give their patients an early warning.
Before that can happen, Malkin and Wirth must overcome some problems with their own technology. Because their nanoparticle-packed columns are so narrow, it takes a tremendous amount of pressure to push a brew of proteins through them.
Malkin is sure that his colleagues will rise to the challenge. Over time, the pace of protein separation will catch up to the incredible speed of high-end analyzers. When that happens, biotech research will shift into a higher gear.
Monday, September 8, 2008
Neural nanomachines project funded by NIH's EUREKA program
EUREKA, an acronym for Exceptional, Unconventional Research Enabling Knowledge Acceleration, is intended to boost exceptionally innovative research.
Biodesign Institute researcher John Chaput and Ira A. Fulton School of Engineering associate professor Rudy Diaz each have received $1.2 million research grants from the new, high-impact NIH program. The EUREKA program represents the NIH’s increased emphasis on supporting unconventional, paradigm-shifting research.
“EUREKA projects promise remarkable outcomes that could revolutionize science,” says Elias Zerhouni, NIH’s director. “The program reflects NIH’s commitment to supporting potentially transformative research, even if it carries a greater-than-usual degree of scientific risk.”
Adds ASU President Michael Crow: “The National Institute of Health’s decision to fund these key biomedical research projects not only speaks to the intellectual merits of ASU’s outstanding proposals, but also confirms ASU’s success in attracting federal investment in bold, high-risk, high-impact research central to our mission.”
Chaput and Diaz’s projects were two of 38 proposals deemed exceptional. This is an impressive showing for ASU, and it demonstrates the university’s ability to compete with the best and brightest scientists from across the nation.
“The EUREKA competition provided a unique forum for our Biodesign team to develop a transformative platform that represents a convergence of chemistry, biology and informatics,” says John Chaput, a Biodesign Institute researcher and ASU assistant professor in the Department of Chemistry and Biochemistry.
Neural nanomachines
Research to be led by Diaz will focus on assembling nanomachines designed to deliver electrical signals to neurons on command. Applications of the technology would include bio-sensing and delivery devices that could be used to detect and treat a variety of human neurological disorders.
Diaz, an associate professor in the Department of Electrical Engineering and the Center for Nanophotonics in ASU’s Ira A. Fulton School of Engineering, will work professors Thomas Moore and Hao Yan in the Department of Chemistry and Biochemistry. Yan also works in the Center for Single Molecule Biophysics in the Biodesign Institute.
The team’s goal is to gain new insights into the pathological obstruction of neural signals and the development of new and more precise neural-stimulation technology.
With existing technology, viewing the “microscopic dynamics” of what is occurring in the human body at a cellular level “is like observing human activity on Earth from an orbiting satellite,” Diaz says.
Even with the development of laser tweezers and nanoelectrodes, “most of our cellular bio-chemistry knowledge is still extracted from circumstantial evidence,” Diaz says.
The method Diaz’s team proposes would permit “direct interaction with cells at the local level.” That would be achieved with a nanoscale structure that could be injected into the body, targeted to attach itself to certain clusters of cells and then controlled by chemical reactions triggered by light delivered either through the skin or via microscopic optical fibers.
The team will molecularly assemble a nanodevice that is best described as a remotely powered and remotely controlled pacemaker.
It will be built on a DNA chassis that includes antennas for receiving power and commands from the outside world, and batteries to store and deliver that power.
The antennas are built of Noble metal nanospheres that take advantage of the plasmon resonance to amplify and focus light with nanometer precision.
Artificial electrocytes – electric organ cells that work like batteries, such as those that naturally occur in fish such as electric eels – will be constructed from liposomes (fat cells) that will have ion pumps and ion gate molecules incorporated into their lipid membranes.
The whole structure will have to be encapsulated in a DNA “cage” to prevent the components from being short-circuited by the body’s fluids.
Under the correct wavelength of light, the power-receiving antennae would amplify the incident light to drive the electric charging of the artificial electrocyte.
The structure would include a set of plasmonic antennae. These are microscopic metal nanostructures that behave as antennae in the presence of photons (light) the way metal antennas behave in the presence of radio waves.
The antennas would be tuned to a different wavelength and coupled to the ion gates in the membranes to serve as light-activated switches to perform a “gate-opening” process that triggers the discharge of the artificial electrocyte chain, thus delivering an electrical impulse that can stimulate neurons.
The group hopes to prove the functionality of each component independently and to demonstrate that the entire assembly works as designed.
These nanostructures could lead to advanced neuro-imaging sensors operating at the cellular scale. Such nanosensors delivered to their targets by chemical tags, or during surgical intervention, could reveal new details about the transmission of neural signals and of their pathological interruption.
The light-powered artificial electrocyte could become a critical tool for improving microsurgery, and advancing the understanding of cellular biology.
Discovering ‘hidden’ proteins
During his four-year research project, Chaput will lead a Biodesign Institute team on a project that plans to search the human genome for regions of DNA that contain important, but as of yet unidentified genetic information.
If successful, Chaput’s project may confirm the possible existence of novel protein-coding regions that remain hidden in the shadows of the classic proteome. Determining how and when such proteins are made could have a major impact in diseases, such as cancer, by helping us to understand how cellular function is deposited in our genomes.
Within the code of life, three polymers – DNA, RNA and proteins – provide nearly all of the information content. Each is made from a slightly different set of chemical building blocks, and the exact sequence of these blocks within each chain carries out the instructions of the genetic code. Fifty years ago, Francis Crick, co-discoverer of the DNA double helix, first postulated the “central dogma” of molecular biology, where DNA information is transcribed to make RNA, and RNA is translated to make proteins.
The bounty of the Human Genome Project has identified nearly 25,000 genes. It’s estimated that the human body could make more than a million different proteins, the majority of which remain to be discovered. This entourage of proteins, the proteome, is ultimately responsible for everything good or bad that is related to human health and disease.
Chaput’s team, which includes fellow Biodesign colleagues Sudhir Kumar and Bertram Jacobs, has produced tantalizing clues that suggest there may be many proteins hidden within the DNA sequences of our genome. Together, they will combine their expertise in molecular and cellular biology, bioinformatics and virology to uncover how and when such proteins are made.
“We have developed a combined experimental-bioinformatics approach that allows us to quickly search entire genomes for sequences that enhance the translation of a downstream gene,” Chaput says. “By determining the identity and location of these motifs, it should be possible to determine when specific genes are being made and possibly discover new genes that contribute to our proteome. Since many of these genes will likely be made by non-traditional methods, this technology will also allow us to investigate new mechanisms of protein translation.”
The motifs they hope to identify help recruit ribosomes, the protein translation machinery of the cell, to the correct translation start site on the RNA message. By identifying these landing sites, the team can use bioinformatics to learn where these motifs are located in the genome.
This information will enable Chaput’s team to create an annotated map of the human genome showing all possible locations where protein translation could occur.
Friday, September 5, 2008
NIH's $42M in EUREKA Awards Backs 'Omics, Biomedical Resarch
[Source: By a GenomeWeb staff reporter , GenomeWeb News] - Nearly 40 biomedical and biotech researchers have been awarded a total of roughly $42 million under the National Institutes of Health’s EUREKA program, which seeks to fund “innovative” research that could have an “extraordinarily significant impact” on science, NIH said today.
The Exceptional, Unconventional Research Enabling Knowledge Acceleration (EUREKA) program grants funds to scientists who are seeking novel hypotheses that “tackle major methodological or technical challenges,” and this round includes genomics, proteomics, and mRNA studies, among others.
"EUREKA projects promise remarkable outcomes that could revolutionize science," NIH Director Elias Zerhouni said in a statement. He said EUREKA “reflects NIH’s commitment to supporting potentially transformative research, even if it carries a greater than usual degree of scientific risk."
Researchers landing funding under this EUREKA program announcement will receive around $200,000 per year for up to four years, depending on the availability of funds.
This round of NIH EUREKA funding will be administered under the National Institute of General Medical Sciences, The National Institute of Mental Health, the National Institute on Drug Abuse, and the National Institute of Neurological Disorders and Stroke.
"EUREKA is an experiment in how to attract, identify, and support particularly creative approaches that, if successful, could move science forward dramatically," NIGMS Director Jeremy Berg said in a statement. “One way EUREKA does this is through a specialized application and review process focusing on the significance and innovation of the proposal.”
Awardees receiving funding under NIGMS include:
John Chaput, Arizona State University, Tempe, "Discovering a Hidden Proteome in the Human Genome";
Daniel Chiu, University of Washington, "Super-Resolution Imaging with Difference Deconvolution Microscopy";
Laurence Hurley, University of Arizona, Tucson, "Establishing a Molecular System for Drug Targeting of Transcriptional Control";
Masayori Inouye, University of Medicine & Dentistry of New Jersey/Robert Wood Johnson Medical School, "The Method for Determination of Membrane Protein Structures Without Purification";
Lee Makowski, University of Chicago, "MADMAX: Precise Measurement of Conformational Changes in Proteins";
William Moerner, Stanford University, "Three-Dimensional Super-Resolution Imaging in Living Cells Using Single-Molecule Active Control";
John Sedat, University of California, San Francisco, "Enabling High-Resolution Imaging Deep in Live Tissue with Adaptive Optics";
Charles Stebbins, Rockefeller University, "Exploiting a Bacterial Nano-Syringe for Protein Therapeutics";
Brian Strahl, University of North Carolina, Chapel Hill, "A High-Throughput Approach Towards Deciphering the Histone Code"; and
Michael Stowell, University of Colorado at Boulder, "Self Assembled Lipid Icosohedra for High-Throughput Membrane Protein Structure Determination."
The National Institute of Mental Health is funding programs including:
Todd Lencz, Feinstein Institute for Medical Research, "Identifying Molecular Subtypes of Schizophrenia: A Novel Genomic Approach";
Andras Jagy and Hongkui Zeng, Allen Institute for Brain Science, "Generation and Characterization of Novel and Highly Specific Neuronal Subtype TRA"; and
Yi Eve Sun, University of California, Los Angeles, "A Novel Approach to Identify Neuronal mRNA Targets for Individual microRNAs."
The National Institute of Neurological Diseases and Stroke is funding research by Beverly Davidson, University of Iowa, “RNA Aptamers for Brain Delivery.”
More information about the EUREKA program is available here.
Tuesday, August 19, 2008
Power3 Medical Products, Inc. Provides Progress Report – NuroPro® Clinical Validation Study of Serum Biomarkers for Alzheimer’s Disease
Power3 is currently conducting a 300-patient clinical validation study of its NuroPro® blood serum test for Alzheimer’s and Parkinson’s disease in collaboration with Dr. Marwan Sabbagh, the Director of Clinical Research at the Cleo Roberts Center of Clinical Research at the Sun Health Research Institute in Sun City, Arizona. “The preliminary results of the Power3’s study look very promising. Clinicians around the world look forward to adding a tool to diagnose and treat Alzheimer’s earlier and therefore give the best care to their patients,” says Dr. Sabbagh. To date, 92 Alzheimer and Control patient samples have been analyzed in Power3’s CLIA certified laboratory and have demonstrated high sensitivity and specificity in the diagnosis of Alzheimer’s disease.
“This study confirms Power3’s panel of Neurodegenerative biomarkers’ ability to diagnose Alzheimer’s disease with superior sensitivity and specificity with results in the 95% range. Additionally, the current study validates Power3’s collection, storage, shipping, processing, and biostatistical analysis methods,” says Dr. Essam Sheta, the Director of Power3’s CLIA laboratory. Power3 expects to conclude the initial Alzheimer’s validation study in September 2008 and publish the validation study results soon after.
“Power3 is planning to expand its validation study for NuroPro® to include two additional clinical sites within the U.S. Larger patient cohorts of different ethnic and environmental backgrounds will strengthen the validity of NuroPro’s® applicability in the diagnosis of neurodegenerative diseases,” Steven B. Rash, Chief Executive Officer, commented. Mr. Rash added “This study confirms that Power3 is rapidly approaching the stage to commercializing the first ever blood serum proteomic tests for the diagnosis of neurodegenerative diseases. These encouraging Alzheimer’s test results, and the numerous validation studies that are currently underway for Parkinson’s disease, ALS, and similar neurological disorders, demonstrates our commitment to bringing these tests to market in late 2008 or early 2009. We believe this test will be a major breakthrough for patients and physicians, as it will offer a means to detect neurodegenerative diseases at their earliest stages, allowing physicians to begin treatment at stages which will produce more positive outcomes.”
In addition to the Alzheimer’s clinical validation study being conducted in collaboration with Dr. Sabbagh, the Company continues its ongoing Parkinson’s validation study under the direction of the principal investigator, Dr. Katerina Markopoulou at the Research Institute at the University of Thessaly, Greece. Power3 expects to conclude this Parkinson’s validation study in September and will publish the results soon after.
Monday, July 14, 2008
Power3 Reports on NuroPro® Study
To date, Power3 has analyzed 73 patient samples for the international validation study provided by the University of Thessaly School of Medicine, in Greece, to confirm previous clinical validation studies completed in the United States. The previous study from a US patient population demonstrated that the blood serum protein biomarkers used in the NuroPro® diagnostic test have the ability to consistently distinguish between Parkinson’s disease patients and normal control subjects.
The samples from the University of Thessaly have demonstrated that changes in the blood serum concentration of the protein biomarkers were consistent with previous Power3 results obtained from US Parkinson’s disease patients. As part of the current validation study, Power3 has standardized its methods for collection, storage, shipping, processing, and biostatistical analysis. This study confirms Power3’s ability to reproduce its Parkinson’s disease diagnostic-test results with superior sensitivity and specificity in the 95% range. Power3 expects to strengthen the validation study with samples from over 100 Greek patients by September 2008.
Power3 is also conducting an additional 300-patient clinical validation study of its NuroPro® blood serum test for Parkinson’s and Alzheimer’s disease in collaboration with Dr. Marwan Sabbagh, the Director of Clinical Research at the Cleo Roberts Center of Clinical Research at the Sun Health Research Institute in Sun City, Arizona.
“The potential of the Power3 study cannot be understated. Patients with Alzheimer’s and Parkinson’s disease will benefit by having earlier diagnosis and treatments resulting in an overall better outcome,” says Sabbagh. To date, 69 patient samples have been analyzed. Power3 expects to provide an interim report on this study in July 2008 and complete this validation study in September 2008.
Katerina Markopoulou, Assistant Professor of Neurology at the University of Thessaly, commented: “The available data regarding the sensitivity and specificity of the protein biomarkers identified by Power3 for the diagnosis of Parkinson’s disease are very promising. The validation of these findings in larger patient cohorts of different ethnic backgrounds will provide additional important information regarding NuroPro’s® applicability in the diagnosis of neurodegenerative diseases.”
Steven B. Rash, Chief Executive Officer, commented, “This study provides further support we are rapidly approaching the stage to commercializing the first ever blood serum proteomic tests for the diagnosis of neurodegenerative diseases. These encouraging Parkinson’s tests results and the numerous validation studies that are currently underway for Alzheimer’s disease, ALS, and similar neurological disorders, confirm our commitment to bringing these tests to market in late 2008 or early 2009. We believe this test will be a major advance for patients and physicians, as it will offer a means to detect neurodegenerative diseases at their earliest stages without a painful and complicated spinal tap procedure.”
Tuesday, July 1, 2008
Consultant in TGen Development Helps Bring Luxembourg, Three US Institutions Together
Luxembourg is home to the world’s largest steel company, the world’s highest per-capita income, and, according to a Mercer survey released earlier this month, holds the title of the world’s safest city.
And in recent years, Luxembourg has sought another global distinction, that of a top-tier life sciences sector. Earlier this month, the world’s sole remaining grand duchy — and Europe’s lowest-taxed country — took a key step toward developing a “center of excellence” for bioscience when it announced it had established a trans-Atlantic series of collaborations with three US-based institutions:
The Partnership for Personalized Medicine, headed by Leland Hartwell, a 2001 Nobel laureate and president of the Fred Hutchinson Cancer Research Center in Seattle;
Another Seattle research center, the Institute for Systems Biology, whose president Leroy Hood co-founded biotech giant Amgen; and
The Arizona-based Translational Genomics Research Institute, or TGen, whose president and scientific director Jeffrey Trent once served as scientific director at the National Human Genome Research Institute of the National Institutes of Health.
The Institute for Systems Biology will collaborate with the University of Luxembourg to create the Center for Systems Biology Luxembourg. The two plan to complete a personalized human genome sequencing map for at least 100 subjects, in hopes of creating new methods for understanding the role genetic variations play in disease. ISB and the university also plan to develop integrated systems proteomics, RNA and cell analysis tools, and methods based on the institute’s discovery of protein blood “fingerprints” and single-cell characteristics reflecting the physiological state of the body's 50 major organs.
In addition, the Partnership for Personalized Medicine will join with TGen, the Biodesign Institute at Arizona State University, and the Fred Hutchinson Cancer Center on research projects to develop molecular diagnostics for lung cancer.
Luxembourg — which said it will spend $200 million toward the collaboration — is a client of PricewaterhouseCoopers, which represented the European country in the two years of discussions with principals of the participating institutions that culminated in the June 6 announcement.
Gerry McDougall, leader of PricewaterhouseCoopers’ Health Sciences practice, spoke recently with BioRegion News about the US institutions’ partnership with the government of Luxembourg, as well as its broader pursuit of the life sciences.
What are Luxembourg’s attractions to life sciences institutes and companies?
They have a very conscious, a very deep strategy in diversifying their economy. And they’re looking to do that around the knowledge economy, but specifically in the biotech sector. The major part of their economy is financial services, and they’re doing quite well. I think they have one of the largest [gross domestic products] per capita in the world [Luxembourg recorded the world’s highest gross national income per capita in 2006 with $71,240, according to the World Bank — Ed.]. They want to diversify that economy, and they’re really looking at a long-term strategy. They want to invest in research and development, in biomedical research, increase their investment over time, link that investment to education and healthcare, and create economic development on a longer-term scale.
A 2006 PricewaterhouseCoopers report found that Luxembourg enjoyed the lowest taxes in Europe. How crucial was that factor in establishing the relationships with Luxembourg?
To be honest with you, this is a completely separate project. That’s news to me. But it doesn’t surprise me, because of their wealth, and their ability to make things incredibly attractive from a business standpoint.
You said Luxembourg wants to diversify its economy. How is it concentrated today?
The majority of their economy is financial services and steel. Their economy was predominantly steel up to the 1960s and ‘70s. For a multitude of reasons, they lost their global competitiveness with Asia and India, and they diversified into financial services, which grew incredibly fast. Today the predominance of their economy is the financial services sector. They also have logistics and technology, so they’re looking to diversify into this area of growth, the life sciences.
Also in recent years, Luxembourg has drawn top global technology companies that include Microsoft and Skype. Does this life sciences initiative augur more of a change to the sciences for Luxembourg?
Absolutely. They’re looking at this as an area to get into, the biomedical sciences, and they have a longer-term strategy for that.
How did you come to be involved in the initiative with Luxembourg?
[Luxembourg officials] contacted PwC … at a BIO conference several years ago, and asked me to go out and speak about economic diversification in life sciences in February of last year. I talked about a couple of case studies, one of them being TGen in Phoenix, Ariz. That began a discussion for us to work with the Luxembourg government — PwC US and PwC Luxembourg — to facilitate some discussions with US institutions in creating strategic partnerships or strategic alliances.
In October of last year, we facilitated discussions with four or five US institutions, and [memorandums of understanding] were signed with three of them. And then we worked with the US institutions and the Luxembourg government on planning and due diligence related to the strategic alliances, and we facilitated that. And now they have these agreements. That’s how we got to where we are today.
What presence, if any, have the institutions involved in this effort had in Luxembourg until now?
Jeff Trent, the president and chief scientific officer [of TGen] — several of his faculty had some research alliances with individual investigators in Luxembourg. But that was not the catalyst; that was more of a coincidence.
TGen has served to spark or catalyze Arizona’s life sciences effort over roughly the past decade. How much was that a factor in Luxembourg looking to hook up with TGen?
Very much so. [The government of Luxembourg] did their own global due diligence related to this strategy. And in their research, TGen emerged as a case study, and that’s why they contacted me, because of my role in the creation of TGen [McDougall helped develop TGen as a consultant hired by a working group of academic, business, and civic leaders that successfully drew the institute to Arizona by raising $90 million over five months in 2002 — Ed.]. They looked at that as a really good example of how, where you don’t have critical mass, you can actually create something unique if you’re focused. You can be a player. That was very key to them in determining their strategy.
For TGen, does the Luxembourg consortium represent a different area of specialization, or build on something TGen already does in Phoenix?
Absolutely. [Biobanking] is a core competency that they have. The translational Genomics Research institution, they have very sophisticated biorepositories. That was one of the reasons why they were selected for this initial project.
Dr. Trent is the co-PI on the Atlas project, which is the project that is collecting oncology specimens around the country for [the National Cancer Institute].
Where will the consortium carry out its research? In facilities in Luxembourg, or within facilities of the American partner institutions?
It’s a combination. The goal is for knowledge transfer over the next three to five years, so that Luxembourg has the world-class sophistication to do these types of research — proteomics and the like in systems biology. Some of that will be done in the US, and Luxembourg scientists will be trained in the US, to then … re-establish themselves back in Luxembourg once the infrastructure is in place. The combination of activity will be done in the US and Luxembourg, with the goal and the plan of getting self-sustaining in Luxembourg at the end of these projects.
Any discussion at this point of how many additional people the institutions will need to carry out the research?
The specifics around the number of [full-time equivalent staffers] are still being worked out right now. And they’re being integrated into the growth plans of Luxembourg around their biotechnology initiatives, with the [Centre de Recherche Public-Santé, or Public Research Center for Health], the University of Luxembourg, and health care systems.
How will Luxembourg attempt to complement what has been done elsewhere in Europe? And to what extent is this competitive with other European countries?
They’re an incredibly sophisticated government, and they’re looking at unique and unmet needs in the healthcare system. So one of the things they want to focus on initially is molecular diagnostics, and become a center of excellence around molecular diagnostics, in order to enable the early detection of diseases. So they’re not trying to compete in deep established areas in the pharmaceutical or device areas. They’re trying to create their niche where they can take advantage of their geographic location. So they don’t see this as competitive.
These are joint projects with Luxembourg scientists and physicians working with US scientists and physicians. The disease focus and the projects were selected collaboratively. Lung cancer, for example, has emerged as an area [where] new techniques in proteomics have the physicians and scientists very optimistic that … an early diagnostic can be created. So they were developed collaboratively and complementary to where Luxembourg is heading.
You cited Luxembourg’s commitment to increasing research. Can you quantify how much that economic segment has increased in the past five years?
They’re looking to increase by percentage of GDP. I think they’re approaching 1 to 1.5 [percent], and they want to double that over the next several years, with R&D being up to 3 percent of GDP, which is consistent with the [national] strategy. And so that’s what the underpinning of this is.
How far back has Luxembourg sought to increase its presence in biotechnology?
They have research institutions in Luxembourg; they call them CRPs. And that’s been kind of their foundation. This has probably been several years in the making, and, now they’ve just accelerated that by creating these strategic alliances.
There was some concern a few years back about the level of public education in biotech, and there was talk about stepping that up. How has Luxembourg addressed the issue?
They’re putting a great deal of investment into education. The University of Luxembourg is expanding its programs, both at the undergraduate and graduate level, dramatically. They’re expanding the campus, and that is definitely one of the pillars of this strategy: To increase their education not only of the human resources talent pool within the country, but also the society. There are going to be outreach programs as well related to all of these projects.
The consortium has said Luxembourg will spend $200 million toward the projects over a three-year period. How much additional investment is that expected to leverage?
At this point, I don’t have a number on that. It’s meant to be a long-term strategy. They want to be self-sustaining within the country, so this is about knowledge transfer and long-term strategic relationships with these organizations. It will include a discussion of renewals and spinoff companies, but right now, there isn’t a number tied to it.
What role, if any, will the European Union play?
Luxembourg [works] within the region. They’re so centrally located, so [for] all these projects in lung cancer and some of the future therapeutic areas that Dr. Hood will look at, they will need to collaborate with the greater region of Belgium, France, and Germany. Luxembourg is strategically positioned right in the middle of 4 million people. They’re very close to European cities. So it’s going to be key that this is a European initiative. It has to go beyond the borders of Luxembourg.
The University of Luxembourg is the single academic research university in the country. How important was it, as a result, to bring institutes from the US into this effort?
The university’s expansion has been a recent phenomenon. Their investment in the University of Luxembourg is [because] they’re creating an institute in systems biology in the future, and that was a coincidence of the link with the Institutes for Systems Biology in Seattle with Dr. Lee Hood.
As the press release says, that’s a great synergy. But when we began this, we were not aware of their expansion programs when we were linking them. It was more about Dr. Hood’s work around personalized medicine … It was more the scientific projects themselves, about personalized medicine and Dr. [Leland] Hartwell and the Partnership for Personalized Medicine. It was a necessity to create a state-of-the-art biorepository to be able to do that project, as well as Dr. Hood’s project, which will need biospecimens as well. It was more about world-class excellence than it was about the existing infrastructure in place.
On the planned biobank, who would run the facility? A government entity? A public-private group?
It’s going to be a separate foundation that will run the IBBL. It will be funded by the government, but it will be independent.
In terms of cost, have any figures been broken out for the cost of the biobank or the other two components?
No. They’re really looking at it as a whole, not as individual projects.
Are there locations in place for any of the three proposed projects?
The two research projects — the Institute for Systems Biology, and the Commission on Lung Cancer — those would be at the CRP Santé. The ISB projects would be coordinated through the University of Luxembourg. And then the IBBL, the Integrated Biorepository Bank of Luxembourg, would be an entity to be formed and located in Luxembourg.
For the biobank, have any institutions agreed to send samples for collection?
Not as of yet. There have been some discussions, but it hasn’t been created. And there are some very good working relationships with the surrounding countries, and some very large hospital systems.
What are the next steps for the consortium partners?
They are developing implementation plans, and moving forward as aggressively as possible [to] past this announcement, and get to reach scientific milestones, and hopefully clinical applications in the next few years.
What’s the timeframe for ramping up on these three initiatives?
They want to be fully operational within six to nine months.
What’s the potential for additional US or European institutions to join any of these efforts?
I think this is a great model. We have very complementary strategies, and these chronic diseases have no borders. They are built to be long-term and sustainable relationships over time. And I think it has a very high likelihood that that’s going to happen. Luxembourg is a wonderful partner for these US institutions. These relationships are with the ministers of economy and foreign trade; culture, higher education, and research; and health. That is unprecedented. As they expand their biotechnology initiatives, it would be a strong possibility that additional relationships could be established, in the US or elsewhere.
Tuesday, June 3, 2008
A research team at the University of Arizona is hard on Tethys' heels
[Source: Bernadette Tansey, Chronicle Staff Writer] - An Emeryville biomedical company is about to market a test that it hopes will reduce the terrible health toll of the U.S. diabetes epidemic and, at the same time, slash the nation's costs for medical care.
The diagnostic test to be launched next month by Tethys Bioscience is designed to pick up early signs that a patient will develop the most common type of diabetes - while there's still time to prevent that from happening.
Lifestyle changes such as exercise and a healthier diet have proven to delay the onset of Type 2 or "adult-onset" diabetes, a systemic malfunctioning of energy metabolism that increases the risk of heart attacks, kidney damage, vision loss and other debilitating ailments.
Tethys chief executive Mickey Urdea founded the company in 2002 to develop tests to predict such illnesses so doctors can help their patients ward them off. In addition to diabetes, Tethys has also focused on danger signs for cardiovascular disease and hip fractures. He calls the approach "personalized predictive medicine."
"We think it's the start of a revolution in medical care," Urdea said. "We're spending so much money in this country on diseases, and we don't have to if we can prevent them."
Tethys studied blood samples banked in Finland and Denmark from hundreds of people whose health history was then tracked for years by epidemiologists looking at the onset of diabetes. Among the subjects who developed the disease, Tethys looked for proteins in the blood that were different from those in people who remained free of diabetes. The company found a group of 7 to 15 proteins that, taken together, indicated an increased risk.
Tethys plans to present the data backing its new test on June 6, at the annual meeting of the American Diabetes Association in San Francisco. The association estimates that the total U.S. cost of medical care for diabetes in 2007 was $116 billion. That includes not only treatments such as insulin, but also kidney dialysis, amputations and other measures to deal with the consequences of diabetes. About 20.8 million people in the United States have diabetes, by the association's count. But it also estimates that 54 million more have a condition called prediabetes and may not be aware of it. Damage to the heart and other organs already may be occurring in those people, the ADA says.
Dr. Michael German, clinical director of the UCSF Diabetes Center, said doctors currently have no tool to precisely determine which of their patients are on the road to diabetes. Physicians can estimate the danger by looking at strong risk factors such as obesity, blood glucose levels and a family history of diabetes, he said. Doctors tell all such patients to improve their health habits, but the success rate of such advice is not great, German said. A clear test result warning patients that their individual risk is high could have a significant impact on diabetes prevention, he said.
"Having this information might be a significant motivation for people," German said. In addition to diet and exercise, which are by far the most effective measures, doctors also can prescribe medications to help keep diabetes at bay. German has done consulting work for Tethys.
Urdea said Tethys is likely to be the first company to market a new predictive test for Type 2 diabetes. "We expect competition as time goes on," he said. He estimates that people whose blood shows they're on the high end of Tethys' risk score could be as much as 60 percent more likely to develop Type 2 diabetes within five years.
Tethys plans to seek Food and Drug Administration approval, which might encourage health plans to pay for the test. The company has not yet named a price. But Tethys estimates that each test administered could save health care payers more than $10,000, assuming that patients who find out they are at high risk improve their health habits and avoid the need for expensive diabetes treatments.
That assumption should be tested to see if patients actually would change their ways, said Christian Vaisse, a UCSF associate professor of medicine who studies the genetics of diabetes. The health care system might spend its money more wisely, and benefit more people, by making sure that everyone gets a cheap blood sugar test every year to see if they already have diabetes, he said. Of the 20.8 million people in the United States who have diabetes, about 6.2 million don't know it, the American Diabetes Association estimates. Vaisse said many don't find out until the damage becomes apparent in their eyes, kidneys, nerves or heart.
Vaisse said prediabetes can be detected by an inexpensive oral glucose tolerance test. After the patient swallows a sugar cube, clinicians measure how fast the sugar levels in the blood subside. "It's clear it's not 100 percent predictive, but it is very sensitive," he said.
Urdea said Tethys is continuing to study its test and its potential to improve health care. The company will gauge whether the test, developed through studying patterns among white, middle-aged Europeans, will have the same predictive value in the diverse U.S. population or in children.
A research team at the University of Arizona is hard on Tethys' heels. Professor Serrine Lau at the university's College of Pharmacy said she and her colleagues are about six months away from finishing work on their own test for Type 2 diabetes risk. Their test detects a modification in blood proteins when the level of glucose in the blood starts to get too high, she said. Chains of sugar molecules are grafted onto the proteins as the body tries to absorb the excess glucose.
Lau said, however, that the Tethys team is also taking the right approach toward finding a predictive test for diabetes. Having several different tests could be a boon to medical treatment and research, she said. Comparisons among the results of different tests can help validate the data and lead to new insights, Lau said.
"They could be very complementary," she said.
Thursday, April 24, 2008
UA Researchers Tackling Unsolved Questions about Protein Structures

[Source: Deborah Dawn, BIO5] - A University of Arizona research team is exploring the evolutionary origins of protein structures. Their findings help us better understand how proteins evolved to carry out the instructions encoded in the genes of every living thing.
Protein molecules are made up of chains of amino acids. These chains bend and fold into a dizzying array of three-dimensional shapes and structures, depending on the order of the amino acids in a given chain. Those varied structures are part of what allow the proteins—which are assembled based on instructions coded in DNA—to regulate everything from an organism's growth and metabolism to the ways messages are transmitted from cell to cell. Protein structures are at the heart of how organisms function.
However, the evolution of those structures is still poorly understood, because there are few observed examples of proteins that have clearly evolved from one shape to another. "The origin of the diversity of protein structures is a major unsolved problem," explains BIO5 member Matthew H.J. Cordes, an associate professor of Biochemistry and Molecular Biophysics at the UA.
Cordes' lab is solving that problem. Two graduate students in his lab, Christian M. Roessler and Branwen M. Hall, have located protein molecules in two different viruses that have dramatically different structures: one protein has a helical, or corkscrew shape, while the other is shaped more like a hairpin. Yet these very different proteins have similar amino acid sequences and perform similar functions--binding to DNA to help the viruses replicate and spread--making it likely that they had a common ancestor.
"Somehow, mutations converted the corkscrew structure to the hairpin structure," Cordes says of the finding, which was recently reported in the Proceedings of the National Academy of Sciences.
While this isn't the first example of structural differences among proteins with a common ancestor, it may be the most dramatic natural example of related proteins retaining clear similarity in amino acid sequence while undergoing major reorganization of their structure. "This finding strongly confirms that evolutionary processes produce new protein shapes," Cordes says. "It could become a textbook example of the reality and beauty of evolutionary changes in structure." He adds that some proteins in this family with the hairpin shape bind to DNA more strongly than those with the corkscrew shape, though it is too early to tell if this is always the case. It's not yet known whether such an advantage helped drive the hairpin structure's evolution.
Cordes' graduate students found their protein pair via an unusual method: Roessler and Hall used a stepping-stone technique to make a series of small "jumps" among closely related proteins, following minute structural changes from one protein to another until they "landed" at a protein that was dramatically different from the one they'd started with, yet was still related to it.
Cordes' lab is now working out the details of the specific mutations that might have caused their two proteins to diverge from one another. They also plan to use their stepping-stone technique to shed light on the evolutionary links among other proteins.
"This is like space exploration," Cordes says. "We're journeying through the protein universe, step by step."
Tuesday, November 13, 2007
Coalition joins diabetes battle
“Right now, current indicators – biomarkers – of type 2 diabetes are not well-defined, and most such markers are only reliably detected in people who have already been diagnosed with the disease,” says Serrine Lau, a professor at UA’s College of Pharmacy and a member of the BIO5 Institute. “Finding these clues, which will allow for the early treatment and possible avoidance of the complications associated with the disease, is the goal of our research.”
The principle researchers on the project include UA’s Serrine Lau, George Tsaprailis and Craig Stump; Randy Nelson and Mike Mobley from ASU’s Biodesign Institute; and ASU kinesiology chair Larry Mandarino, who directs the Center for Metabolic Biology in the College of Liberal Arts and sciences.
Lau spearheads the team’s investigation using cutting-edge technologies to discover and validate new biomarkers to detect pre-type-2 diabetes. It is a collaborative project between UA’s BIO5 Institute and ASU’s Biodesign Institute supported by the Technology and Research Initiative Fund (TRIF). TRIF is a special investment in higher education made possible by passage of state Proposition 301 in November 2000.
“Our project is unique in the country,” Lau says. “First, collaborations between our two groups of experts enable us to combine exceptional intellectual and technological resources to address the problem. Second, we are conducting a highly targeted discovery investigation, which is guided by very well-defined clinical protocol. Third, we have a broader patient sample. Similar projects elsewhere are investigating patients who have already been diagnosed with diabetes, but we are looking at a more random sample of the population, and trying to learn how to predict who will develop diabetes.”
“We have the technologies and tools in place now to construct a detailed molecular signature of diabetes,” says Randy Nelson, who heads the Molecular Biosignatures Analysis Unit at ASU’s Biodesign Institute. “By studying the changes in both the expression and structure of proteins related to diabetes, we can determine their contribution to the disease process.”
Nelson is an expert in proteomics, a scientific discipline that studies changes in protein composition – generally in biofluids such as blood and urine – and how these changes relate to disease.
“With the completion of the human genome project, we now understand that genomics alone is insufficient to fully understand cellular biochemistry,” Lau says. “It is the proteins that are the workhorses in regulating biological events.”
Researchers use state-of-the-art technology, including protein sequencing by mass spectrometer, which is an instrument used to determine the composition of a physical sample by generating a spectrum representing the masses of sample components. The BIO5/Biodesign team uses mass spectrometers to identify proteins and their functional states, as well as to measure the quantity of particular proteins. For example, someone with a disease may be producing too much of a given protein that would normally be present in lower amounts in a healthy individual.
“As a clinician treating diabetes, this research is particularly exciting,” says another study participant, Craig Stump, chief of the section of endocrinology, diabetes and hypertension at the UA College of Medicine. “We’ve always used a ‘shotgun approach’ to preventing diabetes – we know we have been overtreating some people and undertreating others. Knowing a patient’s individual risk for diabetes will allow physicians to offer highly specific recommendations to avert the disease. It’s going to change lives.”
“The investigation is challenging, overarching and sometimes it can be intimidating,” Lau says. “But we now realize that it is the path we have to take. It is essential that we approach this in a cooperative and global manner.”
Wednesday, October 17, 2007
Virginia G. Piper Charitable Trust and Flinn Foundation launch $45M initiative to develop personalized diagnostics
World-renowned scientist Dr. Lee Hartwell, 2001 Nobel laureate and director of Fred Hutchinson Cancer Research Center, has been recruited to lead this effort. The Hutchinson Center, based in Seattle, is a leader in using molecular diagnostics for the early detection and clinical management of cancer and other diseases. In addition to his current position as president and director of Fred Hutchinson Cancer Research Center, he will chair the Partnership executive committee, which includes Dr. George Poste, director of the Biodesign Institute at Arizona State University, and Dr. Jeffrey Trent, president and scientific director of the Translational Genomics Research Institute (TGen). "It is a tremendous opportunity for me to be a part of this new model for improving health while reducing health care costs that is being funded by the Piper and Flinn foundations," Hartwell said. "The collaboration between TGen, the Biodesign Institute at ASU, other institutions in Arizona and Fred Hutchinson Cancer Research Center brings together enormous expertise to tackle major challenges in bringing new science and technology to disease management."
The cornerstone of the Partnership is the creation of the Virginia G. Piper Center for Personalized Diagnostics that draws upon the scientific strengths of two of the state's leading bioscience entities, TGen and the Biodesign Institute at ASU, each of which will contribute significant laboratory space to the effort. The Piper Center will utilize bioinformatics and high-performance computing expertise at both institutions, existing nanotechnology and imaging expertise at the Biodesign Institute, and supercomputing resources through ASU's Ira A. Fulton School of Engineering. Additionally, an industrial scale, high-throughput proteomics production facility will be established that taps expertise at both TGen and the Biodesign Institute at ASU in robotics, protein analysis and computing.
Hartwell's involvement provides the Piper Center with opportunity to draw on the Hutchinson Center's extensive capabilities in health economics and the design of clinical and public-health trials through consultative and collaborative relationships. "The Piper trustees made this investment because Dr. Hartwell has a vision to transform the prevention, diagnosis and treatment of disease," said Dr. Judy Jolley Mohraz, president and CEO of the Piper Trust. "That vision draws together scientists, clinicians, engineers, statisticians, insurers and regulators to work collectively to make health care more targeted and affordable. This initiative holds the promise of making a difference in the quality of life for people here in Arizona and throughout the world."
According to John Murphy, president and CEO of the Flinn Foundation, biomarker discovery and diagnostic development could ultimately lead to earlier disease detection and more precise disease management. "To leverage Arizona's institutional assets, the Flinn Foundation's grant commitment to TGen will link Arizona's research universities, health care providers, research institutes and industry partners throughout the state to support the collection and storage of biospecimens and drive Arizona-centric demonstration projects," Murphy said.
Approximately 50 percent of the Flinn Fund for Arizona Proteomics Research will be available to promote research collaborations to leverage the state's significant institutional resources in this field, Murphy added, with the balance supporting the creation of a high-throughput proteomics production facility. Proteomics is a promising and cutting-edge field that studies proteins and their functions in the body. The proteomics production facility will focus on discovering new proteins for the development of diagnostic tests for patients with cancer or other illnesses. These tests could ultimately lead to earlier disease detection and more precise disease management.
Even though the necessary technologies to develop personalized diagnostic tests are available, barriers such as the expense of clinical trials and difficulty obtaining clinical samples have significantly slowed the development process. The Partnership will focus on the development, testing and validation of new molecular diagnostic tools and the approval and distribution of these tools for widespread clinical use. This will be accomplished through a series of collaborative demonstration projects that integrate key health organizations. "The Holy Grail of personalized medicine includes blood-based tests that improve diagnosis and help direct clinical care," said Trent. "The unparalleled opportunity the Partnership provides is to expand the magnitude of proteomic studies across a spectrum of key clinical questions." The Partnership includes recruitment of new faculty and will engage national and international partners to ensure developments are rapidly commercialized. "With the team of scientific and clinical research excellence we are assembling, our goal is to transform medicine from the current 'one size fits all' approach to one that is targeted around a patient's unique genetic and molecular profile," Poste said.
Partnerships formed with large health care systems and disease-focused foundations will facilitate the implementation and validation of molecular diagnostics in clinical settings, as well as close ongoing interaction between scientists and clinicians. Health care systems will benefit from newly developed diagnostics through the most cost-effective use of medical treatments, while patients and the public in general will enjoy greater overall health outcomes. ASU President Michael Crow added that this endeavor "promises to become a shining example of how multiple partners can work together to address a critical need in human health and accelerate solutions that extend beyond our own community."
Tuesday, October 9, 2007
BIO5 and Biodesign Institute seek early detection of Type 2 diabetes
Lau spearheads the team’s investigation using cutting-edge technologies to discover and validate new biomarkers to accurately detect pre-type 2 diabetes. It is a collaborative project between UA’s BIO5 Institute and ASU’s Biodesign Institute, supported by the Technology and Research Initiative Fund, known as TRIF. TRIF is a special investment in higher education made possible by passage of state Proposition 301 in November 2000.
The principal researchers on the project include UA’s Serrine Lau, George Tsaprailis and Craig Stump; Randy Nelson and Mike Mobley from ASU’s Biodesign Institute and ASU West Kinesiology Professor Larry Mandarino. “Our project is unique in the country,” says Lau. “First, collaborations between our two groups of experts enable us to combine exceptional intellectual and technological resources to address the problem. Second, we are conducting a highly targeted discovery investigation, which is guided by very well-defined clinical protocol. Third, we have a broader patient sample. Similar projects elsewhere are investigating patients who have already been diagnosed with diabetes, but we are looking at a more random sample of the population, and trying to learn how to predict who will develop diabetes.”
“We have the technologies and tools in place now to construct a detailed molecular signature of diabetes,” said Randy Nelson, who heads the Molecular Biosignatures Analysis Unit at ASU’s Biodesign Institute. “By studying the changes in both the expression and structure of proteins related to diabetes, we can determine their contribution to the disease process.”
Nelson is an expert in proteomics, a scientific discipline that studies changes in protein composition – generally in biofluids such as blood and urine – and how these changes relate to disease. “With the completion of the human genome project,” says Lau, “we now understand that genomics alone is insufficient to fully understand cellular biochemistry. It is the proteins which are the workhorses in regulating biological events.”
Researchers use state-of-the-art technology including protein sequencing by mass spectrometer, an instrument used to determine the composition of a physical sample by generating a spectrum representing the masses of sample components. The BIO5/Biodesign team uses mass spectrometers not only to identify proteins and their functional states, but also to measure the quantity of particular proteins. For example, someone with a disease may be producing too much of a given protein that would normally be present in lower amounts in a healthy individual. “As a clinician treating diabetes, this research is particularly exciting,” said another study participant, Craig Stump, MD, chief of the section of Endocrinology, Diabetes and Hypertension at the UA College of Medicine. “We’ve always used a shotgun approach to preventing diabetes – we know we have been overtreating some people, and undertreating others. Knowing a patient’s individual risk for diabetes will allow physicians to offer highly specific recommendations to avert the disease. It’s going to change lives.”
“The investigation is challenging, overarching and sometimes it can be intimidating,” continues Lau. “But we now realize that it is the path we have to take. It is essential that we approach this in a cooperative and global manner.”