SomaLogic technology used to discover protein that reverses age-related cardiac hypertrophy in mice

SomaLogic technology used to discover protein that reverses age-related cardiac hypertrophy in mice

5/9/2013

Unbiased proteomic approach helps researchers identify blood-based factor that holds promise for treating human cardiac failure

In a scientific study published today in the journal Cell, a team of researchers led by scientists from the Harvard Stem Cell Institute and including scientists from SomaLogic, describe the discovery of a circulating protein, called GDF-11 (Growth Differentiation Factor 11), that can reverse age-related cardiac hypertrophy in mice. The GDF-11 protein was identified using SomaLogic’s breakthrough proteomics technology.

Age-related cardiac hypertrophy is a major factor in diastolic heart failure, the most common form of heart failure in the United States.  The authors of the Cell paper found evidence suggesting that a blood-based circulating factor that maintains normal cardiac size is either diminished or loses its effectiveness as the body ages. The researchers demonstrated that such a factor exists by using mouse models of cardiac hypertrophy, and subsequently identified a candidate factor by combing through metabolites, lipids and proteins in the blood. Their protein analysis, using SomaLogic’s SOMAscan™ assay, revealed several proteins whose levels of expression change with age, and this led to the discovery of GDF-11. The researchers then demonstrated that treating older mice with a recombinant version of the GDF-11 protein can rapidly reverse age-related cardiac hypertrophy. Studies aimed at extending these observations to humans are underway.

“It has been technically challenging to identify specific proteins of interest out of the complex mixture of proteins that circulate through the body, especially those that are associated with diseases of aging,” said Prof. Richard T. Lee, an investigator at the Harvard Stem Cell Institute, a cardiologist at Brigham and Women’s Hospital and, one of the senior authors of the Cell paper. “Working with SomaLogic scientists to deploy their new proteomic technology in this study allowed us to do such screening rapidly and effectively.”

A more complete description of the work published in Cell can be found in the Harvard Magazine. An abstract of the manuscript, “Identification of Growth Differentiation Factor 11 as a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy,” is available at the journal site (note: subscription required for the whole paper). A video explaining the work and its findings is available here.

Alex Stewart and Britta Singer of SomaLogic are co-authors of the Cell paper, along with significant contributions from the SOMAscan assay and bioinformatics groups. SomaLogic scientists and their colleagues at UCSF (including Dr. Peter Ganz) have independently found preliminary evidence that GDF-11 deficiency is a potential biomarker for assessing the risk of heart failure in humans, work that was presented at the American Heart Association 2012 Scientific Sessions.


Researchers publish initial analysis of host proteomic response to TB infection and treatment

Researchers publish initial analysis of host proteomic response to TB infection and treatment

4/18/2013

A multi-institute team of researchers led by scientists at SomaLogic announced today the results of a study describing multiple blood-based protein biomarkers that more fully reveal the body’s response to pulmonary tuberculosis (TB) infection and its successful  treatment. Their work, which is based on the application of the SOMAscan™ assay, is published today in the open-access scientific journal PLOS ONE.

Globally, tuberculosis kills 1.4 million a year and infects almost nine million annually, second only to HIV/AIDS. Despite significant research, a full understanding of the biology of TB infection, host response, and drug treatment remains elusive. Such knowledge would help tremendously in the identification of potential new drug or diagnostic targets, and adds to our understanding of the biological processes associated with successful therapy.

“To understand the biology of TB infection and treatment, we surveyed the human proteome to find significant changes in the levels of different blood proteins before and after the intensive phase of TB treatment for active pulmonary TB in patients from Kampala Uganda enrolled in a study led by the Center for Disease Control TB Trials Consortium,” said Urs Ochsner, head of the Infectious Diseases Research Group at SomaLogic, and corresponding author on thePLOS ONE paper. “Our goal was to gain new insights into TB, its treatment, and the healing processes the body uses following effective treatment.”

Among the protein changes identified in this research are several that have not been previously reported to be associated with tuberculosis infection and its treatment. These findings offer an intriguing glimpse into how the human body responds to both the TB organism itself as well as “repair” work following successful treatment. More information can be found in the PLOS ONE manuscript, which is available freely under the journal’s open access policies.

The researchers are currently extending these studies further, as part of a Gates Foundation Tuberculosis Biomarkers grant received last year.


Academic collaborators present findings from use of SOMAscan for cancer biomarker discovery

Academic collaborators present findings from use of SOMAscan for cancer biomarker discovery

4/3/2013

Academic scientists from major biomedical research institutions came together on March 25, 2013, to describe how they have applied SOMAscan to their efforts to find disease biomarkers in several types of cancer. The archived webinar is now available for viewing (following registration).

Together with collaborators from both the private and public sectors, SomaLogic scientists have analyzed the proteomics of >8000 blood and tumor tissue samples to discover diagnostic, prognostic and mechanistic biomarkers of malignancy. The web symposium covers part of that work, and features presentations by Harvey Pass, M.D. (New York University  – malignant mesothelioma), Geoff Baird, M.D., Ph.D. (University of Washington, Seattle – lung cancer tissue proteomics), and Randall Brand, M.D. (University of Pittsburgh — pancreatic cancer).


CU-Boulder renames bioscience building in honor of Larry Gold

CU-Boulder renames bioscience building in honor of Larry Gold

2/1/2013

 

On February 1, 2012, the University of Colorado Boulder renamed its MCDB (Molecular, Cellular and Developmental Biology) building the “Gold Bioscience Building” in honor of SomaLogic CEO and Chairman Larry Gold.

Gold has taught at CU-Boulder since 1970, and served as chair of the MCDB department from 1988 to 1992, laying the groundwork for the building that now bears his name, which opened in 1995. He has also launched several successful biotech companies, and received numerous awards for his teaching and his research (full bio here).

“I would like this building to be a place in which great science is done by great faculty with great students and post-docs and others,” Gold said at the renaming ceremony. “I suggest that in this building, named after me today as a beautiful gift, you must ask yourselves ‘why am I doing this and what benefit will people gain from my work.’”

 


SomaLogic and Emerald Bio publish first crystal structure of a SOMAmer bound to its target

SomaLogic and Emerald Bio publish first crystal structure of a SOMAmer bound to its target

11/5/2012

Bedford MA and Boulder CO – November 5, 2012

The molecular structure of a SOMAmer (Slow Off-rate Modified Aptamer) reagent bound to its specific protein has been revealed for the first time by a team of scientists from Emerald Bio and SomaLogic in a manuscript published online this week in the Proceedings of the National Academy of Science (PNAS). Their analyses demonstrate the molecular basis for the vast improvement in protein binding by SOMAmers as compared to traditional aptamers, emphasizing that SOMAmers represent an entirely new class of molecular “affinity reagents” with multiple useful applications in life sciences and medicine.

“The structure of a SOMAmer bound to platelet-derived growth factor B (PDGF-BB) is only the first ‘glimpse’ into the astonishing array of novel molecular shapes that can be achieved by the SOMAmer technology” said Doug Davies, Senior Project Leader at Emerald Bio.  “And it potentially represents an entirely new approach for studying and crystallizing difficult proteins.”

SOMAmers are based on traditional aptamers, short single strands of nucleic acids with specific folded shapes that can bind proteins and other biomolecules. However, the nucleotides used to make SOMAmers are modified by the addition of protein-like “side-chains” to the nucleotide bases themselves, which exponentially increases the number of unique shapes, as well as the binding affinity and specificity of each SOMAmer for its particular protein target.

“We have already demonstrated the huge advantages of SOMAmers for expanding the range of protein targets previously inaccessible to traditional aptamers. The current study with our colleagues at Emerald has now provided us with a clear structural basis of those advantages at a molecular level” said Nebojsa Janjic, Chief Science Officer of SomaLogic. “This work is a compelling demonstration of the enormous potential of SOMAmers as both diagnostic reagents and therapeutics.”

SomaLogic has developed more than 1500 SOMAmer reagents to date, with over 1100 of those already being used (in a multiplex assay called “SOMAscan™”) in biomarker discovery, drug discovery and development, and life sciences. In addition, several individual SOMAmers are under development as potential therapeutic molecules in their own right.  These applications are underway both at SomaLogic and in partnership with leading biopharmaceutical and clinical diagnostic companies.

Several other SOMAmer-protein pair structures have been analyzed in addition to the SOMAmer — PDGF-BB structure described in the PNAS article published today, all demonstrating the unique properties and utility of this new class of binding reagent.

The PNAS article, entitled “Unique Motifs and Hydrophobic Interactions Shape the Binding of Modified DNA Ligands to Proteins Targets” by D.R. Davies et al., will be published the week of November 5, 2012. Once published, the entire manuscript can be accessed at: http://www.pnas.org/cgi/doi/10.1073/pnas.1213933109.

About Emerald Bio
Emerald Bio is a contract research organization that provides collaborative drug discovery services to pharmaceutical companies, biotechnology companies, academic institutions, and government facilities.  Emerald is developing new technologies to study difficult proteins including the engineered expression, protein production and crystal structure determination of GPCRs and integral membrane proteins. The company operates a high-throughput platform leveraged for fragment-based lead discovery and structure-based drug design.

About SomaLogic
SomaLogic, Inc., is a privately held biomarker discovery and clinical diagnostics company based in Boulder, Colorado. The company’s mission is to use its proprietary proteomic technology to develop enhanced protein analysis tools and reagents for the life sciences community, to facilitate biomarker discovery and validation for diagnostic and therapeutic applications, and to develop and commercialize clinical diagnostic products that will improve the delivery of healthcare by offering timely and accurate diagnostic information to physicians and their patients. Further information about SomaLogic can be found at http://test.somalogic.com.

About SOMAscan™/SOMAmers™
SomaLogic’s proprietary SOMAscan™ proteomic technology platform underlies a rapidly growing number of new diagnostic and therapeutic opportunities. The power of the SOMAscan platform comes from its use of a new generation of nucleic acid-based protein-binding reagents, called SOMAmers™ (Slow Off-rate Modified Aptamers). The unique physical properties of SOMAmers empower the accurate detection and measurement of thousands of proteins over a wide range of concentrations in small volumes of biological samples, all in a single SOMAscan assay.


Discovery and validation of a blood-based protein signature for early detection of mesothelioma

Discovery and validation of a blood-based protein signature for early detection of mesothelioma

10/3/2012

A multi-institute team of researchers led by scientists at the NYU Langone Medical Center and SomaLogic, Inc., announced today the discovery and validation of a panel of 13 blood-based protein biomarkers that can detect malignant mesothelioma in even the early stages of this rare but deadly cancer. The work, which is based on a new protein measurement technology developed by SomaLogic, is published today in the open-access scientific journal PLOS ONE.

Malignant mesothelioma is a rare but aggressive lung cancer that can develop several decades after exposure to asbestos. Because it is difficult to diagnose, the majority of cases are not discovered until the disease is far advanced, which results in poor prognosis and limited treatment options. The research described in the PLOS ONE study is aimed at finding a non-invasive test to improve mesothelioma surveillance and detection in high-risk (i.e., asbestos-exposed) patients.  By examining the differences in concentrations in over 1000 proteins in the blood of mesothelioma patients as compared to asbestos-exposed individuals without mesothelioma, the researchers were able to identify a “signature” of 13 specific protein changes that, taken together, indicate the presence of the disease even in early stages.

“The development of  a sensitive and specific serum test for mesothelioma would have an immense impact on the quality and quantity of life for those individuals who have been exposed to asbestos, who are living in uncertainty about whether or not they will develop this devastating disease,” said Dr. Harvey Pass, the Stephen E. Banner Professor of Thoracic Oncology, vice chair of research for the Department of Cardiothoracic Surgery and division chief of General Thoracic Surgery at NYU Langone Medical Center,  and senior author of the PLoS ONE study. “We believe this work is a critical step towards the availability of such a test.”

To find the signature of 13 proteins that indicate the presence of mesothelioma, the researchers applied a new proteomics technology called “SOMAscan™” (see “About” below) that allowed them to widely survey the blood-based protein landscape to find particular changes that indicate the presence of the disease. Unlike genomic studies, blood-based proteins provide a real-time “snapshot” of an individual’s state of health and offer the possibility of detecting a variety of diseases and conditions long before the individual experiences clinical symptoms. However, the fast, accurate and cost-effective measurement of the thousands of proteins that exist in the blood across many different concentrations to find the specific changes of interest has only recently become possible with the availability of the SOMAscan technology.

“We are excited about the application of our SOMAscan assay to this critical, unmet medical need, and have been delighted to work with such accomplished and dedicated researchers and clinicians,” said Dr. Rachel Ostroff, Clinical Research Director at SomaLogic and co-first author of the PLoS ONE study. “We are committed to continuing this important collaboration with Dr. Pass and his colleagues, and expanded studies with more patients are already underway.”

Other contributors to this work include researchers from Mt. Sinai Medical Center in New York, the Libby MT Center for Asbestos Related Diseases, the Karmanos Cancer Center in Detroit, and the Cancer Research Center of Hawaii in Honolulu. The full manuscript is available for viewing and download at http://dx.plos.org/10.1371/journal.pone.0046091.