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
What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
06.12.2016 | Power and Electrical Engineering
06.12.2016 | Earth Sciences
06.12.2016 | Physics and Astronomy