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Posts Tagged ‘Roche Institute of Molecular Biology’


Roche is developing a high-throughput low cost sequencer for NGS

Reporter: Stephen J. Williams, PhD

 

Reported from Diagnostic World News

Long-Read Sequencing in the Age of Genomic Medicine

 

 

By Aaron Krol

December 16, 2015 | This September, Pacific Biosciences announced the creation of the Sequel, a DNA sequencer half the cost and seven times as powerful as its previous RS II instrument. PacBio, with its unique long-read sequencing technology, had already secured a place in high-end research labs, producing finished, highly accurate genomes and helping to explore the genetic “dark matter” that other next-generation sequencing (NGS) instruments miss. Now, in partnership with Roche Diagnostics, PacBio is repositioning itself as a company that can serve hospitals as well.

“Pseudogenes, large structural variants, validation, repeat disorders, polymorphic regions of the genome―all those are categories where you practically need PacBio,” says Bobby Sebra, Director of Technology Development at the Icahn School of Medicine at Mount Sinai. “Those are gaps in the system right now for short-read NGS.”

Mount Sinai’s genetic testing lab owns three RS II sequencers, running almost around the clock, and was the first lab to announce it had bought a Sequel just weeks after the new instruments were launched. (It arrived earlier this month and has been successfully tested.) Sebra’s group uses these sequencers to read parts of the genome that, thanks to their structural complexity, can only be assembled from long, continuous DNA reads.

There are a surprising number of these blind spots in the human genome. “HLA is a huge one,” Sebra says, referring to a highly variable region of the genome involved in the immune system. “It impacts everything from immune response, to pharmacogenomics, to transplant medicine. It’s a pretty important and really hard-to-genotype locus.”

Nonetheless, few clinical organizations are studying PacBio or other long-read technologies. PacBio’s instruments, even the Sequel, come with a relatively high price tag, and research on their value in treating patients is still tentative. Mount Sinai’s confidence in the technology is surely at least partly due to the influence of Sebra―an employee of PacBio for five years before coming to New York―and Genetics Department Chair Eric Schadt, at one time PacBio’s Chief Scientific Officer.

Even here, the sequencers typically can’t be used to help treat patients, as the instruments are sold for research use only. Mount Sinai is still working on a limited number of tests to submit as diagnostics to New York State regulators.

Physician Use

Roche Diagnostics, which invested $75 million in the development of the Sequel, wants to change that. The company is planning to release its own, modified version of the instrument in the second half of 2016, specifically for diagnostic use. Roche will initially promote the device for clinical studies, and eventually seek FDA clearance to sell it for routine diagnosis of patients.

In an email to Diagnostics World, Paul Schaffer, Lifecycle Leader for Roche’s sequencing platforms division, wrote that the new device will feature an integrated software pipeline to interpret test results, in support of assays that Roche will design and validate for clinical indications. The instrument will also have at least minor hardware modifications, like near field communication designed to track Roche-branded reagents used during sequencing.

This new version of the Sequel will probably not be the first instrument clinical labs turn to when they decide to start running NGS. Short-read sequencers are sure to outcompete the Roche machine on price, and can offer a pretty useful range of assays, from co-diagnostics in cancer to carrier testing for rare genetic diseases. But Roche can clear away some of the biggest barriers to entry for hospitals that want to pursue long-read sequencing.

Today, institutions like Mount Sinai that use PacBio typically have to write a lot of their own software to interpret the data that comes off the machines. Off-the-shelf analysis, with readable diagnostic reports for doctors, will make it easier for hospitals with less research focus to get on board. To this end, Roche acquired Bina, an NGS analysis company that handles structural variants and other PacBio specialties, in late 2014.

The next question will be whether Roche can design a suite of tests that clinical labs will want to run. Long-read sequencing is beloved by researchers because it can capture nearly complete genomes, finding the correct order and orientation of DNA reads. “The long-read technologies like PacBio’s are going to be, in the future, the showcase that ties it all together,” Sebra says. “You need those long reads as scaffolds to bring it together.”

But that envisions a future in which doctors will want to sequence their patients’ entire genomes. When it comes to specific medical tests, targeting just a small part of the genome connected to disease, Roche will have to content itself with some niche applications where PacBio stands out.

Early Applications

“At this time we are not releasing details regarding the specific assays under development,” Schaffer told Diagnostics World in his email. “However, virology and genetics are a key focus, as they align with other high-priority Roche Diagnostics products.”

Genetic disease is the obvious place to go with any sequencing technology. Rare hereditary disorders are much easier to understand on a genetic level than conditions like diabetes or heart disease; typically, the pathology can be traced back to a single mutation, making it easy to interpret test results.

Some of these mutations are simply intractable for short-read sequencers. A whole class of diseases, the PolyQ disorders and other repeat disorders, develop when a patient has too many copies of a single, repetitive sequence in a gene region. The gene Huntingtin, for example, contains a long stretch of the DNA code CAG; people born with 40 or more CAG repeats in a row will develop Huntington’s disease as they reach early adulthood.

These disorders would be a prime target for Roche’s sequencer. The Sequel’s long reads, spanning thousands of DNA letters at a stretch, can capture the entire repeat region of Huntingtin at a stretch, unlike short-read sequencers that would tend to produce a garbled mess of CAG reads impossible to count or put in order.

Nonetheless, the length of reads is not the only obstacle to understanding these very obstinate diseases. “The entire category of PolyQ disorders, and Fragile X and Huntington’s, is really important,” says Sebra. “But to be frank, they’re the most challenging even with PacBio.” He suggests that, even without venturing into the darkest realms of the genome, a long-read sequencer might actually be useful for diagnosing many of the same genetic diseases routinely covered by other instruments.

That’s because, even when the gene region involved in a disease is well known, there’s rarely only one way for it to go awry. “An example of that is Gaucher’s disease, in a gene called GBA,” Sebra says. “In that gene, there are hundreds of known mutations, some of which you can absolutely genotype using short reads. But others, you would need to phase the entire block to really understand.” Long-read sequencing, which is better at distinguishing maternal from paternal DNA and highlighting complex rearrangements within a gene, can offer a more thorough look at diseases with many genetic permutations, especially when tracking inheritance through a family.

“You can think of long-read sequencing as a really nice way to supplement some of the inherited panels or carrier screening panels,” Sebra says. “You can also use PacBio to verify variants that are called with short-read sequencing.”

Virology is, perhaps, a more surprising focus for Roche. Diagnosing a viral (or bacterial, or fungal) infection with NGS only requires finding a DNA read unique to a particular species or strain, something short-read sequencers are perfectly capable of.

But Mount Sinai, which has used PacBio in pathogen surveillance projects, has seen advantages to getting the full, completely assembled genomes of the organisms it’s tracking. With bacteria, for instance, key genes that confer resistance to antibiotics might be found either in the native genome, or inside plasmids, small packets of DNA that different species of bacteria freely pass between each other. If your sequencer can assemble these plasmids in one piece, it’s easier to tell when there’s a risk of antibiotic resistance spreading through the hospital, jumping from one infectious species to another.

Viruses don’t share their genetic material so freely, but a similar logic can still apply to viral infections, even in a single person. “A virus is really a mixture of different quasi-species,” says Sebra, so a patient with HIV or influenza likely has a whole constellation of subtly different viruses circulating in their body. A test that assembles whole viral genomes—which, given their tiny size, PacBio can often do in a single read—could give physicians a more comprehensive view of what they’re dealing with, and highlight any quasi-species that affect the course of treatment or how the virus is likely to spread.

The Broader View

These applications are well suited to the diagnostic instrument Roche is building. A test panel for rare genetic diseases can offer clear-cut answers, pointing physicians to any specific variants linked to a disorder, and offering follow-up information on the evidence that backs up that call.

That kind of report fits well into the workflows of smaller hospital labs, and is relatively painless to submit to the FDA for approval. It doesn’t require geneticists to puzzle over ambiguous results. As Schaffer says of his company’s overall NGS efforts, “In the past two years, Roche has been actively engaged in more than 25 partnerships, collaborations and acquisitions with the goal of enabling us to achieve our vision of sample in to results out.”

But some of the biggest ways medicine could benefit from long-read sequencing will continue to require the personal touch of labs like Mount Sinai’s.

Take cancer, for example, a field in which complex gene fusions and genetic rearrangements have been studied for decades. Tumors contain multitudes of cells with unique patchworks of mutations, and while long-read sequencing can pick up structural variants that may play a role in prognosis and treatment, many of these variants are rarely seen, little documented, and hard to boil down into a physician-friendly answer.

An ideal way to unravel a unique cancer case would be to sequence the RNA molecules produced in the tumor, creating an atlas of the “transcriptome” that shows which genes are hyperactive, which are being silenced, and which have been fused together. “When you run something like IsoSeq on PacBio and you can see truly the whole transcriptome, you’re going to figure out all possible fusions, all possible splicing events, and the true atlas of reads,” says Sebra. “Cancer is so diverse that it’s important to do that on an individual level.”

Occasionally, looking at the whole transcriptome, and seeing how a mutation in one gene affects an entire network of related genes, can reveal an unexpected treatment option―repurposing a drug usually reserved for other cancer types. But that takes a level of attention and expertise that is hard to condense into a mass-market assay.

And, Sebra suggests, there’s another reason for medical centers not to lean too heavily on off-the-shelf tests from vendors like Roche.

Devoted as he is to his onetime employer, Sebra is also a fan of other technologies now emerging to capture some of the same long-range, structural information on the genome. “You’ve now got 10X Genomics, BioNano, and Oxford Nanopore,” he says. “Often, any two or even three of those technologies, when you merge them together, can get you a much more comprehensive story, sometimes faster and sometimes cheaper.” At Mount Sinai, for example, combining BioNano and PacBio data has produced a whole human genome much more comprehensive than either platform can achieve on its own.

The same is almost certainly true of complex cases like cancer. Yet, while companies like Roche might succeed in bringing NGS diagnostics to a much larger number of patients, they have few incentives to make their assays work with competing technologies the way a research-heavy institute like Mount Sinai does.

“It actually drives the commercialization of software packages against the ability to integrate the data,” Sebra says.

Still, he’s hopeful that the Sequel can lead the industry to pay more attention to long-read sequencing in the clinic. “The RS II does a great job of long-read sequencing, but the throughput for the Sequel is so much higher that you can start to achieve large genomes faster,” he says. “It makes it more accessible for people who don’t own the RS II to get going.” And while the need for highly specialized genetics labs won’t be falling off anytime soon, most patients don’t have the luxury of being treated in a hospital with the resources of Mount Sinai. NGS companies increasingly see physicians as some of their most important customers, and as our doctors start checking into the health of our genomes, it would be a shame if ubiquitous short-read sequencing left them with blind spots.

Source: http://diagnosticsworldnews.com/2015/12/16/long-read-sequencing-age-genomic-medicine.aspx

 

 

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Physiologist, Professor Lichtstein, Chair in Heart Studies at The Hebrew University elected Dean of the Faculty of Medicine at The Hebrew University of Jerusalem

Reporter: Aviva Lev-Ari, PhD, RN

Professor David Lichtstein Elected Dean of Hebrew University’s Faculty of Medicine

December 2, 2013

Jerusalem — Professor David Lichtstein has been elected dean of the Faculty of Medicine at The Hebrew University of Jerusalem. Professor Lichtstein is the Walter & Greta Stiel Chair in Heart Studies at The Hebrew University. He replaces Professor Eran Leitersdorf, who recently completed his four-year term as dean.

According to Professor Lichtstein, “The Hebrew University’s Faculty of Medicine is devoted to creating innovative teaching, research and patient care programs that will meet the demands of 21st century health care. As global health care moves towaProfessor David Lichtsteinrd prevention, wellness and cost effectiveness, we are adapting how we train the next generation of physicians, nurses, pharmacists and biomedical researchers. Through fruitful collaborations between preclinical and clinical faculty, we are also translating basic biomedical insights into clinical treatments. Thus, the Faculty of Medicine is well-positioned to maintain its leading role in the scientific community of Israel and the world.”

Professor Lichtstein was born in Lodz, Poland, and immigrated to Israel with his family in 1957. As a student at The Hebrew University, he completed a Bachelor’s degree in Physiology and Zoology in 1970, followed by a Master’s degree in Physiology in 1972 and a Ph.D. in Physiology in 1977. He joined the Department of Physiology of The Hebrew University-Hadassah Medical School in 1980 as a lecturer, and received full professorship in 1994. Prof. Lichtstein has held many roles at The Hebrew University and its Faculty of Medicine, including Chairman of the Neurobiology Teaching Division, Chairman of the Department of Physiology, Chairman of the Institute for Medical Sciences and, until recently, Chairman of the Faculty of Medicine. From 2007 to 2011, Professor Lichtstein was the Jacob Gitlin Chair in Physiology at The Hebrew University. In 2011 he was named the Walter & Greta Stiel Chair in Heart Studies at The Hebrew University. He also served as the President of the Israel Society for Physiology and Pharmacology from 1996 to 1999.

From 1977-1979 Professor Lichtstein was a Postdoctoral Fellow at the Roche Institute of Molecular Biology in New Jersey. He was a visiting scientist at the National Institute of Child Health and Human Development (1985-1986) and the Eye Institute (1997-1998) at the National Institutes of Health in Maryland, and a visiting professor at the Toledo School of Medicine in Ohio (2007).

Professor. Lichtstein’s main research focus is the regulation of ion transport across the plasma membrane of eukaryotic cells. His work led to the discovery that specific steroids that were known to be present in plants and amphibians are actually normal constituents of the human body and have crucial roles, such as the regulation of cell viability, heart contractility, blood pressure and brain function. His research has implications for the fundamental understanding of body functions, as well as for several pathological states such as heart failure, hypertension and neurological and psychiatric diseases.

SOURCE

http://www.afhu.org/professor-david-lichtstein-elected-dean-hebrew-universitys-faculty-medicine

Field of Study

Regulation of ion transport across the plasma membrane:
The primary focus of the research in my laboratory is the regulation of ion transport across the plasma membrane of eukaryotic cells. In particular, we study the main transport system for sodium and potassium, the sodium-potassium-ATPase, and its regulation by cardiac steroids.
Specific areas of interest:
Identification of endogenous cardiac steroids in mammalian tissue; The biological consequences of the interaction of cardiac steroids with the sodium-potassium-ATPase; Biosynthesis of the cardiac steroids in the adrenal gland; Effects of endogenous sodium-potassium-ATPase inhibitors on cell differentiation; Determination of the levels of endogenous sodium-potassium-ATPase inhibitors in pathological states, including hypertension, preeclampsia; malignancies (cancer) and manic depressive illnesses; Involvement of the sodium-potassium–ATPase/cardiac steroids system in depressive disorders; Involvement of the sodium-potassium-ATPase/cardiac steroids system in cardiac function; Involvement of intestinal signals in the regulation of phosphate homeostasis; Volume regulation and its involvement in the mitogenic response.
Cardiac Steroids and the Na+, K+-ATPase and Cardiac Steroids
Cardiac steroids, such as ouabain, digoxin and bufalin are hormones synthesized by and released from the adrenal gland and the hypothalamus. These compounds, the structure of which resembles that of plant and amphibian and butterfly steroids, interact only with the plasma membrane Na+, K+-ATPase (Figure 1). This interaction elicits numerous specific biological responses affecting the function of cells and organs.
Topics Currently under investigation include
Cardiac Steroids
  • Ouabain
  • Bufalin
  • Dogoxin
Involvement of the sodium-potassium–ATPase/cardiac steroids system in depressive disorders
Depressive disorders, including major depression, dysthymia and bipolar disorder, are a serious and devastating group of diseases that have a major impact on the patients’ quality of life, and pose a significant concern for public health. The etiology of depressive disorders remains unclear. The Monoaminergic Hypothesis, suggesting that alterations in monoamine metabolism in the brain are responsible for the etiology of depressive disorders, is now recognized as insufficient to explain by itself the complex etiology of these diseases. Data from our and other laboratories has provided initial evidence that endogenous cardiac steroids and their only established receptor, the Na+, K+-ATPase, are involved in the mechanism underlining depressive disorders, and BD in particular. Our study (Biol. Psychiatry. 60:491-499, 2006) has proven that Na+, K+-ATPase and DLC are involved in depressive disorders particularly in manic-depression. We have also shown that specific genetic alterations in the Na+, K+-ATPase α isoforms are associated with bipolar disorders (Biol. Psychiatry, 65:985-991, 2009). Our recent study in this project (Eur. Neuropsychopharmacol. 22:72-729, 2012) showed that drugs affecting the Na+, K+-ATPase/cardiac steroids system are beneficial for the treatment of depression. Hence our work is in accordance to the proposition that mal functioning of the Na+, K+-ATPase/cardiac steroids system may be involved in manifestation of depressive disorders and identify new compounds as potential drug for the treatment of these maladies.
Involvement of the sodium-potassium-ATPase/cardiac steroids system in cardiac function
The classical and best documented effect of cardiac steroids, as their name implies, is to increase the force of contraction of heart muscle. Indeed, cardiac steroids were widely used in Western and Eastern clinical practices for the treatment of heart failure and atrial fibrillation. Despite extensive research, the mechanism underlying cardiac steroids actions have not been fully elucidated. The dogmatic explanation for cardiac steroids-induced increase in heart contractility is that the inhibition of Na+, K+-ATPase by the steroids causes an increase in intracellular Na+ which, in turn, attenuates the Na+/Ca++ exchange, resulting in an increased intracellular Ca++ concentration, and hence greater contractility. However, recent observations led to the hypothesis that the ability of cardiac steroids to modulate a number of intracellular signaling processes may be responsible for both short- and long-term changes in CS action on cardiac function. We are addressing this hypothesis using the zebrafish model and our ability to quantify heart function in-vivo. Heart contractility measurements were performed using a series of software tools for the analysis of high-speed video microscopic images, allowing the determination of ventricular heart diameter and perimeter during both diastole and systole. The ejection fraction (EF) and fractional area changes (FAC) were calculated from these measurements, providing two independent parameters of heart contractility (see attached movie bellow). We are currently testing the effect of cardiac steroids in the presence and absence of intracellular signaling pathways (MAP, AKT, IP3R) inhibitors. Reduction in the steroids ability to increase the force of contraction will serve as the first evidence, in-vivo, for the participation of the signaling processes in the molecular mechanisms responsible for the action of cardiac steroids on heart muscle.
Laboratory Techniques
We employ a broad range of preparations and techniques. These include isolated organs (arterial rings, smooth and cardiac muscle strips) and isolated nerve endings, as well as primary and established tissue-cultured cells. Our studies involve the application of biochemical and immunological techniques (transport and enzymatic activity measurements, RIA, ELISA), molecular biological techniques (e.g., Western and Northern blotting, and PCR), protein purification (HPLC), cellular techniques muscle contractility, cell proliferation and differentiation’ in-vivo measurements of heart contractility and blood flow in Zebrafish and behavior measurements in rodents.

Biography

Education
1970
B.Sc. in Physiology and Zoology, The Hebrew University, Jerusalem, Israel
1970-1972 M.Sc. in Physiology, Department of Physiology, The Hebrew University, Hadassah Medical School, Jerusalem, Israel.
1973-1977
Ph.D., Department of Physiology, Hebrew University Hadassah Medical School, Jerusalem, Israel. (Thesis: “Increased Production of Gamma Aminobutyryl choline in Cerebral Cortex Caused by Afferent Electrical Stimulation” (Thesis Advisors: Prof. J. Dobkin and Prof. J. Magnes).
1977-1979
Postdoctoral Fellow, Department of Physiological Chemistry and Pharmacology, Roche Institute of Molecular Biology, Nutley, New Jersey, U.S.A.
Positions held

1970-1972
Teaching and Research Assistant, Department of Physiology, The Hebrew University, Hadassah Medical School, Jerusalem, Israel
1972-1974 Assistant Instructor, Department of Physiology, The Hebrew University, Hadassah Medical School, Jerusalem, Israel
1975-1977 Instructor, Department of Physiology, The Hebrew University, Hadassah Medical School, Jerusalem, Israel
1977-1979
Postdoctoral Fellow, Department of Physiological Chemistry and Pharmacology, Roche Institute of Molecular Biology, Nutley, New Jersey, U.S.A.
1979-1983
Lecturer, (REVSON fellowship) Department of Physiology, The Hebrew University, Hadassah Medical School, Jerusalem, Israel
1981 (summer)
Visiting Scientist, Department of Physiological Chemistry and Pharmacology, Roche Institute of Molecular Biology, Nutley, New Jersey, USA
1983-1987 Senior Lecturer, Department of Physiology, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
1985-1986
Visiting Scientist, Laboratory of Theoretical and Physical Biology, NICHD, National Institutes of Health, Bethesda, Maryland, USA
1988-1994 Associate Professor, Department of Physiology, The Hebrew University Hadassah Medical School, Jerusalem, Israel
1994-present Professor of Physiology, Department of Physiology, The Hebrew University Hadassah Medical School, Jerusalem, Israel
1997-1998 Visiting Scientist, Laboratory of Mechanisms of Ocular Diseases, NEI, National Institutes of Health, Bethesda, Maryland, USA
2007 (summer)
Visiting Professor, Department of Physiology, Pharmacology, Metabolism and cardiovascular Sciences, Medical Center University of Toledo, Toledo, Ohio, USA
2007-2011 Jacob Gitlin Chair in Physiology, The Hebrew University, Jerusalem, Israel
2011-present ​Walter & Greta Stiel Chair in Heart Studies, The Hebrew University, Jerusalem
Professional Membership
1979-present International Society of Neurochemistry
1979-present Israel Society for Physiological and Pharmacological
1980-present Society of Neurosciences (Europe)
1986-present The American Society of Hypertension
1992-present Israeli Society for Neurosciences
1999-present The American Physiological Society
Editorial Tasks
Serving as a Reviewer for the scientific journals:
American Journal of Hypertension Journal of Neural Transmission
American Journal of Physiology Journal of Neurochemistry
Apoptosis Journal of Pharmacology and Experimental Therapeutics
Biochemical and Biophysical Research Communications Life Sciences
Basic Journal of Physiology and Pharmacology NANO
Brain Research Neurochemistry International
Bioconjugate Chemistry Neuroscience
Cell Calcium Neurotoxicity Research
Clinical Science Pathophysiology
Endocrinology Physiology and Behavior
European Neuropsychopharmacology PNAS
General and Comparative Endocrinology Psychiatry Research
Hypertension Translational Research
Journal of Cell Sciences
University and Other Activities
1982-1985 Chairman of the Neurobiology Teaching Division, The Hebrew University, Jerusalem
1988-1994 Elected representative of the Senior Lecturers and Associate Professors for the University Senate
1989-1997 Member of the admission committee of the Medical School, The Hebrew University, Jerusalem
1990-1996 Member of the Committee for cellular biology of the graduate studies, The Hebrew University, Jerusalem
1992-1996 Member of the Teaching Committee, Faculty of Medicine, The Hebrew University, Jerusalem
1992-1996
Chairman, Department of Physiology, The Hebrew University, Hadassah Medical School, Jerusalem
1994-1997 Member of the Committee for graduate studies, The Hebrew University, Jerusalem
1992-2002
Member of the Management Committee of The Institute for Medical Sciences, Faculty of Medicine, The Hebrew University, Jerusalem
1996-1999
President of the Israel Society for Physiology and Pharmacology
1998- 2002 Chairman, Institute of Medical Sciences, The Hebrew University, Hadassah Medical School, Jerusalem
1999-2002 Member of the Planning and Development Committee of the Faculty of Medicine, The Hebrew University, Jerusalem
2007–Present Elected representative of the Professors for the executive University Senate
2008-2012 Member of the Planning and Development Committee of the Faculty of Medicine, The Hebrew University, Jerusalem
2008-2012 Chairman, Institute for Medical Research Israel-Canada, The Hebrew University, Hadassah Medical School, Jerusalem
2009 – Present Elected member of the Senate to the Executive Committee of the Hebrew University

PUBLICATIONS 2006 – 2012

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Dvela, M., Rosen, H., Ben-Ami, H. C., Lichtstein, D.
American journal of physiology. Cell physiology, 302(2), C442-52, 2012
Goldstein, I., Lax, E., Gispan-Herman, I., Ovadia, H., Rosen, H., Yadid, G., Lichtstein, D.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 22(1), 72-9, 2012
Nesher, M., Shpolansky, U., Viola, N., Dvela, M., Buzaglo, N., Cohen Ben-Ami, H., Rosen, H., Lichtstein, D.
British journal of pharmacology, 160(2), 346-54, 2010
Guttmann-Rubinstein, L., Lichtstein, D., Ilani, A., Gal-Moscovici, A., Scherzer, P., Rubinger, D.
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 42(4), 230-6, 2010
Jaiswal, M. K., Dvela, M., Lichtstein, D., Mallick, B. N.
Journal of sleep research, 19(1 Pt 2), 183-91, 2010
Nesher, M., Dvela, M., Igbokwe, V. U., Rosen, H., Lichtstein, D.
American journal of physiology. Heart and circulatory physiology, 297(6), H2026-34, 2009
Goldstein, I., Lerer, E., Laiba, E., Mallet, J., Mujaheed, M., Laurent, C., Rosen, H., Ebstein, R. P., Lichtstein, D.
Biological psychiatry, 65(11), 985-91, 2009
Nesher, M., Vachutinsky, Y., Fridkin, G., Schwarz, Y., Sasson, K., Fridkin, M., Shechter, Y., Lichtstein, D.
Bioconjugate chemistry, 19(1), 342-8, 2008
Dvela, M., Rosen, H., Feldmann, T., Nesher, M., Lichtstein, D.
Pathophysiology : the official journal of the International Society for Pathophysiology / ISP, 14(3-4), 159-66, 2007
Feldmann, T., Glukmann, V., Medvenev, E., Shpolansky, U., Galili, D., Lichtstein, D., Rosen, H.
American journal of physiology. Cell physiology, 293(3), C885-96, 2007
Chirinos, J. A., Corrales-Medina, V. F., Garcia, S., Lichtstein, D. M., Bisno, A. L., Chakko, S.
Clinical rheumatology, 26(4), 590-5, 2007
Lichtstein, D. M., Arteaga, R. B.
The American journal of the medical sciences, 332(2), 103-5, 2006
Morla, D., Alazemi, S., Lichtstein, D.
Journal of general internal medicine, 21(7), C11-3, 2006
Chirinos, J. A., Corrales, V. F., Lichtstein, D. M.
Clinical rheumatology, 25(1), 111-2, 2006
Deutsch, J., Jang, H. G., Mansur, N., Ilovich, O., Shpolansky, U., Galili, D., Feldman, T., Rosen, H., Lichtstein, D.
Journal of medicinal chemistry, 49(2), 600-6, 2006
Goldstein, I., Levy, T., Galili, D., Ovadia, H., Yirmiya, R., Rosen, H., Lichtstein, D.
Biological psychiatry, 60(5), 491-9, 2006
Chirinos, J. A., Garcia, J., Alcaide, M. L., Toledo, G., Baracco, G. J., Lichtstein, D. M.
American journal of cardiovascular drugs : drugs, devices, and other interventions, 6(1), 9-14, 2006
Rosen, H., Glukmann, V., Feldmann, T., Fridman, E., Lichtstein, D.
Cellular and molecular biology (Noisy-le-Grand, France), 52(8), 78-86, 2006

SOURCE

https://medicine.ekmd.huji.ac.il/En/Publications/publications/Pages/default.aspx?aut=Lichtstein,%20D

 

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