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Dr. Avraham Samson

senior lecturer
Telephone
Bar-Ilan Email
avraham.samson@biu.ac.il
Office
Building A, Room 101
Fields of Interest

Computational Biology, Structural Biology, Bioinformatics, Pharmacology' Drug development, Alzheimer's diseases, Neurobiology

 

Reception Hours
Please schedule by mail or by phone
Academic field
Biochemistry
Pharmacology
Research field
Computational biology and drug discovery
Research Center
Bar-Ilan University Azrieli Faculty of Medicine, Safed
CV

Dr. Avraham Samson heads the Drug Discovery Lab at the Faculty of Medicine of Bar Ilan University. He focuses on the development of computation biology and drug discovery. Dr. Samson earned his bachelor's degree in the Department of Chemistry of Bar-Ilan University, his master's, and doctorate degrees in the Structural Biology department of the Weizmann Institute of Science. He also earned an MBA degree from Bar-Ilan University. He has received honors and awards for his work, and has published over 50 peer-reviewed papers, as well as many more books, book chapters, and conference abstracts. Dr. Samson joined the Faculty of Medicine in 2011 as one of the founding researchers, after spending 5 years as a Post-Doctoral Fellow at Stanford University School of Medicine, in the Department of Structural Biology under the guidance of Nobel prize laureate, Prof. Michael Levitt.

Research

Research Highlights  

In the past years, our team identified and tested several new drug candidates for treating Alzheimer’s disease, hypertension, and cancer. A number of exciting outcomes were achieved which will be translated into medical applications.  Some of research projects are highlighted in the following paragraphs.   

 

Arginase as aNew Target in the Treatment of Alzheimer’s Disease 

The precise cause of Alzheimer`s disease remains a mystery despite decades of intensive investigation, and one reason that no long-term effective drug has been developed is the shortage of pharmaceutical targets in the brain. In this study, we proposes a new pharmaceutical target, namely arginase which is the central enzyme of the urea cycle. Arginase is associated with the development of neurodegenerative diseases, and too much of it has been shown to contribute to Alzheimer's disease. Remarkably, targeting arginase and blocking its action reverses the development of Alzheimer`s disease in rodent models. Consequently, the new target represents a promising direction for clinical development. To read more, please click here http://odem.md.biu.ac.il/nrr.pdf 

 

 

Norvaline: A novel Alzheimer's Disease-modifying agent. 

Alzheimer’s disease is a slowly progressive, neurodegenerative disorder that is characterized by severe decline in memory, thinking and reasoning skills. Recently, we developed a new drug that targets arginase, namely norvaline, and showed it reverses memory decline and brain tissue loss in a mouse model of Alzheimer’s disease. Furthermore, norvaline restores the blood brain barrier integrity in a mouse model of Alzheimer’s Disease. As such, norvaline is a new therapeutic agent against Alzheimer's disease, and clinical trials have begun to test the efficacy in human patients. To read more, click here: http://odem.md.biu.ac.il/ijms.pdf 

  

Reduction of High Blood Pressure with Norvaline.  

Growing evidence suggests that increased arginase activity affects vital processes in various systems such as blood pressure and diabetes. Remarkably, we showed that norvaline also reduces blood pressure and promotes urine formation in rats with high blood pressure.  The same drug did not affect the blood pressure of mice with normal blood pressure. As such, norvaline is a potential new therapeutic agent against high blood pressure. To read more, click here: http://odem.md.biu.ac.il/bmri.pdf 

 

 Invasion and Metastasis: The Elusive Hallmark of Cancer. 

Hallmarks of cancer are essential abilities that are acquired by human cancer.  The hallmarks include survival, resistance, evasion, immortality, and invasion and metastasis. In this study, we showed that invasion and metastasis is the most important hallmark, as it alone is the leading cause of mortality even following surgical removal of the main tumor, if possible. Interestingly, most scientific effort is funneled towards the development of drugs that target other hallmarks.  Little and not enough effort is invested towards finding drugs against invasion and metastasis. Consequently, we recommends focusing more research around invasion and metastasis, and develop new drugs that target this important hallmark. To read more, click here: http://odem.md.biu.ac.il/onogene.pdf 

 

A new protein motif: κ-helix. 

Proteins are essential building blocks of cells, and consist of well-defined 3D folds.  Protein folds, in turn, are responsible for their function and interaction.   Recently, we uncovered a new protein motif, and named it κ-helix.  The κ -helix, adopts a 3-fold rotational symmetry, and is responsible for the lock-and-key interaction of proteins involved in cellular communication, such as SH3, WW, profilin, MHC-II, EVH1 and GYF domains.  Based on a geometric analysis of 255 proteins, we found that κ-helices are characterized by a distinctive rotations and vary between different orientations, expand the current molecular understanding of the cellular communication in disease and health. To read more, click here: http://odem.md.biu.ac.il/bioinformatics3.pdf 

 

 Understanding the onset of Alzheimer’s disease. 

Over the past decade, several studies showed that toxic amyloid-peptides produced in Alzheimer`s disease bind to brain receptors and block signal transmission. To better understand the onset of Alzheimer's diseases, we deciphered the 3D structure of solubilized amyloid-peptides before they form β-structures, and aggregate in the brain of Alzheimer's patients. We found that water soluble amyloid-peptides adopt a helical structure which is very different from the β-sheet like structure  found in the brain of affected subjects affected.  The conversion from α to β structure is driven by a kink at position K28. The structure sheds light on the structural changes of proteins that characterize Alzheimer’s disease. To read more, click here: http://odem.md.biu.ac.il/fonar.pdf 

 

 Molecular motion of nerve channel is blocked by scorpion and spider toxins. 

To better understand the function of nerve channels receptors, we calculated their molecular motion using powerful computers equipped with hundreds of processors. The calculations revealed a paddle motion responsible for channel function.  Strikingly, the paddle motion was not observed for the channels upon binding of scorpion and spider toxins.  These toxins prevent the molecular motion and block channel activation.  These results shed light on the activation mechanism of nerve channels, and their blocking by scorpion and spider venom. To read more, click here: http://odem.md.biu.ac.il/greenberger.pdf 

 

 Molecular motion is essential for drug action.  

About 70% of drugs used in medicine bind to a family of receptors named the G-protein-coupled receptors (GPCR).  To better understand drug binding and receptor activation, we calculated the motion of several receptors of this family involved in blood pressure regulation, inflammation, etc. The calculation revealed that drug binding and contraction on one side of the receptor lead to dilation and cavity formation on the other side.  Furthermore, electric-charge calculations revealed that the binding site acts like a magnet to attract specific drugs. Altogether, these results illustrate how drug binding induces motion which in turn initiates action. To read more, click here: http://odem.md.biu.ac.il/kolan.pdf 

 

What is a protein fold? 

Together with Prof. Michael Levitt, the 2013 Nobel Laureate of Chemistry, we wrote a review in the prestigious journal "Annual Review of Biophysics" in collaboration with Prof. Rachel Kolodny of Haifa University, and Dr. Leonid Pereyeslavets a postdoc in the Levitt lab.  The review is titled:  "On the universe of protein folds", and discusses the physical rules governing protein structure and defines the term protein fold as a the structure adopted by a family of proteins. Notably, the definition of a fold is subjective to classification, and a fold lies in the eye of the beholder. To read more, click here: http://odem.md.biu.ac.il/kolodny.pdf 

 

Publications

Peer Reviewed Publications

Polis B., Samson A.O. "Neurogenesis versus neurodegeneration: the broken balance in Alzheimer's disease" 2021 Neural Regeneration Research. 16(3):496-497. PubMed

 

Meirson T., Bomze D., Samson A.O. "κ-helix and the helical lock and key model: A pivotal way of looking at polyproline II" 2020 Bioinformatics. 36(12):3726-3732. PubMed

 

Gilinsky M.A., Polityko Y.K., Markel A.L., Latysheva T.V., Samson A.O., Polis B., Naumenko S.E., "Norvaline Reduces Blood Pressure and Induces Diuresis in Rats with Inherited Stress-Induced Arterial Hypertension" 2020, Biomed Research International. 2020:4935386. PubMed

 

Polis B., Gurevich V., Bloch N., Bloch N., Samson A.O."Arginase Inhibition Supports Survival and Differentiation of Neuronal Precursors in Adult Alzheimer's Disease Mice" 2020, International Journal of Molecular Sciences. 21(3). PubMed

 

Polis B., Samson A.O."Role of the metabolism of branched-chain amino acids in the development of Alzheimer's disease and other metabolic disorders." 2020, Neural Regeneration Research. 15(8):1460-1470. PubMed

 

Meirson T., Gil-Henn H., Samson A.O."Invasion and metastasis: the elusive hallmark of cancer.", 2020, Oncogene. 39(9):2024-2026 PubMed

 

Meirson T., Bomze D., Kahlon L., Gil-Henn H., Samson A.O. "A helical lock and key model of polyproline II conformation with SH3", 2020, Bioinformatics. 36(1):154-159. PubMed

 

Polis B., Gilinsky M.A., Samson A.O."Reports of L-Norvaline Toxicity in Humans May Be Greatly Overstated.", 2019, Brain Sciences. 17;9(12). PubMed

 

Polis B., Gurevich V., Assa M., Samson A.O."Norvaline Restores the BBB Integrity in a Mouse Model of Alzheimer's Disease", 2019, International Journal of Molecular Sciences. 18;20(18). PubMed

 

Atrahimovich D., Samson A.O., Barsheshet Y., Vaya J., Khatib S., Reuveni E. "Genome-wide localization of the polyphenol quercetin in human monocytes", 2019, BMC Genomics. 20(1):606. PubMed

 

Polis B., Srikanth K.D., Gurevich V., Gil-Henn H., Samson A.O. "L-Norvaline, a new therapeutic agent against Alzheimer's disease", 2019, Neural Regeneration Research. 14(9):1562-1572. PubMed

 

Polis B., Samson A.O. "Arginase as a Potential Target in the Treatment of Alzheimer's Disease", 2018, Advances in Alzheimer's Disease. 7(4), 119-140.

 

Fonar G., Polis B., Meirson T., Maltsev A., Samson A.O. "Subcutaneous Sustained-Release of Poly-Arginine Ameliorates Cognitive Impairment in a Transgenic Mouse Model of Alzheimer's Disease", 2018, Advances in Alzheimer's Disease. 7(4), 153-182.

 

Polis B., Srikanth K.D., Elliott E., Gil-Henn H., Samson A.O. "L-Norvaline Reverses Cognitive Decline and Synaptic Loss in a Murine Model of Alzheimer's Disease.", 2018, Neurotherapeutics. 15(4):1036-1054. PubMed

 

Atrahimovich D, Samson A.O., Khattib A., Vaya J., Khatib S. "Punicalagin Decreases Serum Glucose Levels and Increases PON1 Activity and HDL Anti-Inflammatory Values in Balb/c Mice Fed a High-Fat Diet", 2018, Oxid Med Cell Longev. 2018:2673076. PubMed

 

Fonar G., Polis B., Meirson T., Maltsev A., Elliott E., Samson A.O. "Intracerebroventricular Administration of L-arginine Improves Spatial Memory Acquisition in Triple Transgenic Mice Via Reduction of Oxidative Stress and Apoptosis.", 2018, Translational Neuroscience. 9:43-53. PubMed

 

Meirson T., Genna A., Lukic N., Makhnii T., Alter J., Sharma V.P., Wang Y., Samson A.O., Condeelis J.S., Gil-Henn H. "Targeting invadopodia-mediated breast cancer metastasis by using ABL kinase inhibitors.", 2018, Oncotarget. 9(31):22158-22183. PubMed

 

Zattelman L., Regev R., Usaj M., Reinke P.Y.A., Giese S., Samson A. O., Taft M.H., Manstein D.J., Henn A. "N-terminal splicing extensions of the human MYO1C gene fine-tune the kinetics of the three full-length myosin IC isoforms.", 2017, Journal of Biological Chemistry. 292(43):17804-17818. PubMed

 

Glantz-Gashai Y., Meirson T., Reuveni E., Samson A. O. "Virtual screening for potential inhibitors of Mcl-1 conformations sampled by normal modes, molecular dynamics, and nuclear magnetic resonance.", 2017, Drug Design Development and Therapy. 11:1803-1813. PubMed

 

Meirson T., Samson A. O., Gil-Henn H. "An in silico high-throughput screen identifies potential selective inhibitors for the non-receptor tyrosine kinase Pyk2.", 2017, Drug Design Development and Therapy. 11:1535-1557. PubMed

 

Aran A., Segel R., Kaneshige K., Gulsuner S., Renbaum P., Oliphant S., Meirson T., Weinberg-Shukron A., Hershkovitz Y., Zeligson S., Lee M.K., Samson A. O., Parsons S.M., King M.C., Levy-Lahad E., Walsh T. "Vesicular acetylcholine transporter defect underlies devastating congenital myasthenia syndrome", 2017, Neurology. 88:1021-1028. PubMed

 

Falik Zaccai T.C., Savitzki D., Zivony-Elboum Y., Vilboux T., Fitts E.C., Shoval Y., Kalfon L., Samra N., Keren Z., Gross B., Chasnyk N., Straussberg R., Mullikin J.C., Teer J.K., Geiger D., Kornitzer D., Bitterman-Deutsch O., Samson A. O., Wakamiya M., Peterson J.W., Kirtley M.L., Pinchuk I.V., Baze W.B., Gahl W.A., Kleta R., Anikster Y., Chopra A.K. "Phospholipase A2-activating protein is associated with a novel form of leukoencephalopathy." 2017, Brain. 140:370-386. PubMed

 

Glantz-Gashai Y., Meirson T., and Samson A. O. "Normal Modes Expose Active Sites in Enzymes", 2016, PLoS Comput Biol. 21,12. PubMed

 

Dabour R., Meirson T., and Samson A. O. "Global antibiotic resistance is mostly periodic" 2016, J Glob Antimicrob Resist. 7:132-134. PubMed

 

Atrahimovich D., Khatib S., Sela S., Vaya J., and Samson A. O. "Punicalagin Induces Serum Low-Density Lipoprotein Influx to Macrophages" 2016, Oxid Med Cell Longev. 2016:71242-51. PubMed

 

Reuveni E., Samson A. O., and Giuliani A., "Principal component analysis of mouse genomes unravels strong genetic robustness during evolution" 2015, International J of Medical Biotech and Genetics. 1:1-6. PubMed

 

Weinberg-Shukron A., Renbaum P., Kalifa R., Zeligson S., Ben-Neriah Z., Dreifuss A., Abu-Rayyan A., Maatuk N, Fardian N, Rekler D, Kanaan M, Samson A.O., Levy-Lahad E, Gerlitz O, and Zangen D. "A mutation in the nucleoporin-107 gene causes XX gonadal dysgenesis" , 2015, The Journal of Clinical Investigation. 125:4295-304. PubMed

 

Fonar G., and Samson A. O. "NMR structure of the water soluble Aβ17-34 peptide", 2014, Bioscience Reports. 34(6):e00155 Pubmed

 

Maatuk N., Glantz-Gashai Y., Rotman M., Baydany M., Fonar G., Shechvitz A., Shemer K., Peleg A., Reuveni E., and Samson A. O. "PHI-DAC: protein homology database through dihedral angle conservation", 2014, Bioinformatics. 31(2):292-4 PubMed

 

Greenberger M. M., and Samson A. O. "Normal mode dynamics of voltage-gated K+ channels: gating principle, opening mechanism, and inhibition", 2014, Journal of Computational Neuroscience. 38(1):83-8 PubMed

 

Kolan D., Fonar G., and Samson A. O."Elastic network normal modes reveal the GPCR activation mechanism", 2013, Protein: Structure, Function, and Bioinformatics. 82(4):579-86 PubMed

 

Kolodny R., Pereyeslavets L., Samson A. O., and Levitt M. "On the universe of protein folds", 2013, Annual Review of Biophysics, 42, 559-582. PubMed

 

Maatuk N., and Samson A. O. "Modeling the binding mechanism of Alzheimer's Aβ(1-42) to nicotinic acetylcholine receptors based on similarity with snake α-neurotoxins.", 2012, Neurotoxicology, 50, 2243-8. PubMed

 

Samson A. O., and Levitt M., "Normal modes of prion proteins: from native to infectious particle", 2011, Biochemistry, 50, 2243-8. PubMed

 

Samson A. O., and Levitt M., " Protein segment finder: an online search engine for segment motifs in the PDB", 2009, Nucleic Acid Research, 37 (Database issue), D224-8. PubMed

 

Samson A. O., and Levitt M., "Inhibition mechanism of the acetylcholine receptor by α-neurotoxins as revealed by normal mode dynamics", 2008, Biochemistry, 47, 4065-4070. PubMed

 

Rosen O., Samson A.O., and Anglister J., "Correlated mutations at gp120 positions 322 and 440: implications for gp120 structure", 2008, Proteins, 71, 1066-70. PubMed

 

Rosen O., Samson A. O., Sharon M., Zolla-Pazner S., and Anglister J., "Response to Matters Arising ", 2006, Structure, 14, 649-651.

 

Samson A. O., and Anglister J., "2D-measurement of proton T relaxation in unlabeled proteins: α-bungarotoxin complex with acetylcholine receptor peptide", 2005, Biochemistry, 44, 10926-10934. PubMed

 

Biron Z., Khare S., Samson A.O., Naider F., and Anglister J. "A monomeric 310-helix is formed in water by a 13-residue peptide representing the neutralizing determinant of HIV-1 on gp41" , 2002, Biochemistry, 41, 12687-12696. PubMed

 

Yassin L., Samson A.O., Halevi S., Eshel M., and Treinin M., "Mutations in the extracellular domain and in the membrane spanning domains interfere with nicotinic acetylcholine receptor maturation", 2002, Biochemistry, 41, 12329-12335. PubMed

 

Samson A.O., Scherf. T., Eisenstein M., Chill J., and Anglister J., "The mechanism for acetylcholine receptor inhibition by α-neurotoxins and species-specific resistance to α-bungarotoxin revealed by NMR", 2002, Neuron, 35, 319-332. Pubmed

 

Yao Y., Wang J., Viroonchatapan N., Rothe E., Samson A.O., Chill J., Anglister J., and Wang Z. "Yeast expression and NMR analysis of the extracellular domain of muscle nicotinic acetylcholine receptor α-subunit", 2002, Journal of Biological Chemistry, 277(15), 12613-12621. Pubmed

 

Samson A.O., Chill J., Rodriguez E., Scherf T., and Anglister J., "NMR mapping and secondary structure determination of the major acetylcholine receptor α-subunit determinant interacting with α-bungarotoxin", 2001, Biochemistry, 40, 5464-5473. Pubmed

 

    Books

    Polis B., Samson A.O. "Arginase as a potential target in the treatment of Alzheimer's disease" (2018) Lambert academic publishing.
     

     

    Book chapters

    Polis, B. Samson A. O. A New Perspective on Alzheimer's Disease as a Brain Expression of a Complex Metabolic Disorder. 2019, In: Wisniewski T., editor. Alzheimer's Disease. Brisbane (AU): Codon Publications. Chapter 1. Pubmed
     
     
    Samson A. O., Scherf T., Eisenstein M., Chill J. H., and Anglister J., "The mechanism for acetylcholine receptor inhibition by α-neurotoxins and species specific resistance to α-bungarotoxin revealed by NMR" 2004, Cholinergic mechanisms, function and dysfunction, p.45-54, Taylor & Francis group, UK.
     
     
    Samson A. O., Scherf T., Eisenstein M., and Anglister J., "Interactions of toxins with cholinergic proteins", 2004, Cholinesterases in the second millenium: Biomolecular and Pathological Aspects, p.285-93, Diseño e Impresiones Ltda. press. Pucon, Chile.

     

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    Last Updated Date : 07/01/2021