In a new study, researchers took another step toward that goal by developing a technique able to predict from a blood sample the amount of cathepsins -- protein-degrading enzymes known to accelerate these diseases -- that a specific person would produce.
This patient-specific information may be helpful in developing personalized approaches to treat these tissue-destructive diseases.
“We measured significant variability in the amount of cathepsins produced by blood samples we collected from healthy individuals, which may indicate that a one-size-fits-all approach of administering cathepsin inhibitors may not be the best strategy for all patients with these conditions,” said Manu Platt, an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.
The study was published online on Oct. 19, 2012 in the journal Integrative Biology. This work was supported by the National Institutes of Health, Georgia Cancer Coalition, Atlanta Clinical and Translational Science Institute, and the Emory/Georgia Tech Regenerative Engineering and Medicine Center.
Platt and graduate student Keon-Young Park collected blood samples from 14 healthy individuals, removed white blood cells called monocytes from the samples and stimulated those cells with certain molecules so that they would become macrophages or osteoclasts in the laboratory. By doing this, the researchers recreated what happens in the body—monocytes receive these cues from damaged tissue, leave the blood, and become macrophages or osteoclasts, which are known to contribute to tissue changes that occur in atherosclerosis, cancer and osteoporosis.
Then the researchers developed a model that used patient-varying kinase signals collected from the macrophages or osteoclasts to predict patient-specific activity of four cathepsins: K, L, S and V.
“Kinases are enzymes that integrate stimuli from different soluble, cellular and physical cues to generate specific cellular responses,” explained Platt, who is also a Georgia Cancer Coalition Distinguished Cancer Scholar. “By using a systems biology approach to link cell differentiation cues and responses through integration of signals at the kinase level, we were able to mathematically predict relative amounts of cathepsin activity and distinguish which blood donors exhibited greater cathepsin activity compared to others.”
Predictability for all cathepsins ranged from 90 to 95 percent for both macrophages and osteoclasts, despite a range in the level of each cathepsin among the blood samples tested.
“We were pleased with the results because our model achieved very high predictability from a simple blood draw and overcame the challenge of incorporating the complex, unknown cues from individual patients’ unique genetic and biochemical backgrounds,” said Platt.
According to Platt, the next step will be to assess the model’s ability to predict cathepsin activity using blood samples from individuals with the diseases of interest: atherosclerosis, osteoporosis or cancer.
“Our ultimate goal is to create an assay that will inform a clinician whether an individual’s case of cancer or other tissue-destructive disease will be very aggressive from the moment that individual is diagnosed, which will enable the clinician to develop and begin the best personalized treatment plan immediately,” added Platt.
Weiwei A. Li, who received her bachelor’s degree from the Coulter Department in 2010, also contributed to this study.
Research reported in this publication was supported in part by the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) under award number UL1TR000454 and the Office of the Director of the NIH under award number 1DP2OD007433. The content is solely the responsibility of the principal investigators and does not necessarily represent the official views of the NIH.
CITATION: Park, Keon-Young et al., “Patient specific proteolytic activity of monocyte-derived macrophages and osteoclasts predicted with temporal kinase activation states during differentiation,” Integrative Biology (2012): http://dx.doi.org/10.1039/C2IB20197F.Research News & Publications Office
John Toon | Newswise Science News
The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie
How protein islands form
15.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
Researchers from the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science, the Italian Space Agency (ASI), and the Instituto Geofisico--Escuela Politecnica Nacional (IGEPN) of Ecuador, showed an increasing volcanic danger on Cotopaxi in Ecuador using a powerful technique known as Interferometric Synthetic Aperture Radar (InSAR).
The Andes region in which Cotopaxi volcano is located is known to contain some of the world's most serious volcanic hazard. A mid- to large-size eruption has...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
16.08.2017 | Physics and Astronomy
16.08.2017 | Materials Sciences
16.08.2017 | Interdisciplinary Research