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Yuval Dor

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A simple test to identify diseases from dying cells could save lives; earns Kaye Innovation Award

26/06/2017

Prof. Yuval Dor and Dr. Ruth Shemer receive Kaye Innovation Award for developing a way to detect specific tissue damage from a blood sample

One of the holy grails of medical research is the development of a simple non-invasive test that can detect a variety of diseases with high accuracy. However to date there is no single diagnostic test that fulfills this function.

To solve this problem, Prof. Yuval Dor and Dr. Ruth Shemer  at the Hebrew University of Jerusalem (together with Prof. Ben Glaser, Head of the Endocrinology Department at the Hadassah Medical Center) developed a new blood test that looks for the remnants of dying cells cast off by specific tissue types throughout the body.

When cells die, they release DNA fragments into the circulatory system. The DNA of each type of dying cell carries a unique chemical modification called methylation. By detecting the unique methylation signatures of DNA from the fragments of dying cells, Prof. Dor and Dr. Shemer have established a way to detect multiple disease processes —including diabetes, cancer, traumatic injury and neurodegeneration — in a highly sensitive and specific manner.

Prof. Dor and Dr. Shemer are researchers at the Institute for Medical Research-Israel Canada (IMRIC) in the Hebrew University's Faculty of Medicine. Both earned their PhDs at the Hebrew University.

Developing a rapid blood test to assess multiple diseases simultaneously

A test that accurately pinpoints tissue damage from dying cells’ DNA fragments could hold the key to a variety of medical advances — from a deeper understanding of human tissue dynamics, to earlier detection of life-threatening illnesses, to more efficient monitoring of responses to medical therapies.

Prof. Dor and Dr. Shemer envision a future where the continued research and refinement of their new technology will lead to a universal, rapid, sensitive and quantitative blood test for tissue-specific cell death. This blood test could be used to assess multiple pathologic conditions simultaneously, equivalent to standard blood chemistry panels in use today.

Their paper describing the method and its applications was published in the Proceedings of the National Academy of Sciences, in 2016, drawing considerable interest from the scientific and popular media.

Aurum Ventures MKI Ltd., the technology investment arm of Morris Kahn, provided Yissum, the Technology Transfer arm of the Hebrew University, with $1.2 million of funding for research and development of this new diagnostic approach. Earlier this year, OnTimeBio was founded to make Prof. Dor’s and Dr. Shemer’s vision become a reality.

2017 Kaye innovation Award

In recognition of their work, Prof. Dor and Dr. Shemer were awarded the Kaye Innovation Award for 2017.

The Kaye Innovation Awards at the Hebrew University of Jerusalem have been awarded annually since 1994. Isaac Kaye of England, a prominent industrialist in the pharmaceutical industry, established the awards to encourage faculty, staff and students of the Hebrew University to develop innovative methods and inventions with good commercial potential, which will benefit the university and society. For more information about the 2017 Kaye Innovations Awards, visit http://bit.ly/kaye2017.

About the Hebrew University of Jerusalem

The Hebrew University of Jerusalem, Israel’s leading academic and research institution, is ranked among the top 100 universities in the world. Founded in 1918 by visionaries including Albert Einstein, the Hebrew University is a pluralistic institution where science and knowledge are advanced for the benefit of humankind. For more information, please visit http://new.huji.ac.il/en.

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A simple test to identify diseases from dying cells could save lives; earns Kaye Innovation Award
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New Method Detects Multiple Diseases Via DNA Released From Dying Cells Into Blood

15/03/2016

New blood test uses methylation patterns of circulating DNA from dying cells to detect diabetes, multiple sclerosis, pancreatic cancer, pancreatitis and brain damage, opening up vast possibilities for diagnostic medicine

In a series of experiments involving 320 patients and controls, researchers developed a blood test that can detect multiple pathologies, including diabetes, cancer, traumatic injury and neurodegeneration, in a highly sensitive and specific manner. The novel method infers cell death in specific tissue from the methylation patterns of circulating DNA that is released by dying cells.

The findings are reported in a paper published in the Proceedings of National Academy of Sciences USA, entitled “Identification of tissue specific cell death using methylation patterns of circulating DNA”. The research was performed by an international team led by Dr. Ruth Shemer and Prof. Yuval Dor from The Hebrew University of Jerusalem, and Prof. Benjamin Glaser from Hadassah Medical Center.

Cell death is a central feature of human biology in health and disease. It can signify the early stages of pathology (e.g. a developing tumor or the beginning of an autoimmune or neurodegenerative disease), mark disease progression, reflect the success of therapy (e.g. anti cancer drugs), identify unintended toxic effects of treatment and more. However to date, it is not possible to measure cell death in specific human tissues non-invasively.

The new blood test detects cell death in specific tissues by combining two important biological principles. First, dying cells release fragmented DNA to the circulation, where it travels for a short time. This fact has been known for decades; however since the DNA sequence of all cells in the body is identical, it has not been possible to determine the tissue of origin of circulating DNA, and simple measurements of the amount of circulating DNA is of very limited use. The second principle is that the DNA of each cell type carries a unique chemical modification called methylation. Methylation patterns of DNA account for the identity of cells (the genes that they express), are similar among different cells of the same type and among individuals, and are stable in healthy and disease conditions. For example, the DNA methylation pattern of pancreatic cells differs from the pattern of all other cell types in the body.

The researchers have identified multiple DNA sequences that are methylated in a tissue-specific manner (for example, unmethylated in DNA of neurons and methylated elsewhere), and can serve as biomarkers for the detection of DNA derived from each tissue. They then developed a method to detect these methylated patterns in DNA circulating in blood, and demonstrated its utility for identifying the origins of circulating DNA in different human pathologies, as an indication of cell death in specific tissues. They were able to detect evidence for pancreatic beta-cell death in the blood of patients with new-onset type 1 diabetes, oligodendrocyte death in patients with relapsing multiple sclerosis, brain cell death in patients after traumatic or ischemic brain damage, and exocrine pancreas cell death in patients with pancreatic cancer or pancreatitis.

"Our work demonstrates that the tissue origins of circulating DNA can be measured in humans. This represents a new method for sensitive detection of cell death in specific tissues, and an exciting approach for diagnostic medicine" said Dr. Ruth Shemer of the Hebrew University, a DNA methylation expert and one of the lead authors of the new study.

The approach can be adapted to identify cfDNA derived from any cell type in the body, offering a minimally-invasive window for monitoring and diagnosis of a broad spectrum of human pathologies, as well as better understanding of normal tissue dynamics.

"In the long run, we envision a new type of blood test aimed at the sensitive detection of tissue damage, even without a-priori suspicion of disease in a specific organ. We believe that such a tool will have broad utility in diagnostic medicine and in the study of human biology," said Prof. Benjamin Glaser, head of Endocrinology at Hadassah Medical Center and another lead author of the study.

The work was performed by Hebrew University students Roni Lehmann-Werman, Daniel Neiman, Hai Zemmour, Joshua Moss and Judith Magenheim, aided by clinicians and scientists from Hadassah Medical Center, Sheba Medical Center and from institutions in Germany, Sweden, the USA and Canada who provided precious blood samples of patients.

Support for the research came from the Juvenile Diabetes Research Foundation, the Human Islet Research Network of the NIH, the Sir Zalman Cowen Universities Fund, the DFG (a Trilateral German-Israel-Palestine program), and the Soyka pancreatic cancer fund.

The Institute for Medical Research-Israel Canada (IMRIC), in the Hebrew University of Jerusalem's Faculty of Medicine, is one of the most innovative biomedical research organizations in Israel and worldwide. IMRIC brings together the most brilliant scientific minds to find solutions to the world's most serious medical problems, through a multidisciplinary approach to biomedical research. More information at http://imric.org.

The Hebrew University of Jerusalem is Israel’s leading academic and research institution, producing one-third of all civilian research in Israel. For more information, visit http://new.huji.ac.il/en.

Hadassah-Hebrew University Medical Center is Israel’s leading academic hospital, combining the highest quality of medical care with world-class basic and translational research.  For more information, visit http://www.hadassah-med.com.

REFERENCE: Roni Lehmann-Werman et al. Identification of tissue specific cell death using methylation patterns of circulating DNA. PNAS Early Edition, March 14, 2016. doi:10.1073/pnas.1519286113.

 

New Method Detects Multiple Diseases Via DNA Released From Dying Cells Into Blood
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