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2026

A protein–small molecule conjugate as a bispecific inhibitor of proteases implicated in cancer metastasis

Bahat I, Pinkret Y, Baumann A, Arbely E, Miller A.K, Papo N. Scientific Reports. 2026

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Modulating amyloid-β 42 aggregation and neurotoxicity by Kunitz domains and their derived peptides

Rabinovich M, Lacham-Hartman S, Papo N. New Biotechnology journal 2026

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Engineering selective amyloid precursor protein inhibitors by machine learning and deep mutational scanning

Meiri R, Reuveni O, Levi M, Radisky E, Papo N, Orenstein O. Protein Science 2026

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Machine-learning prediction of affinity and epistasis in the bovine pancreatic trypsin inhibitor–chymotrypsin complex

Tzuri N, Kass I, Orenstein O, Papo N. Protein Science 2026

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Multi-specific targeting of CD44 and the catalytic and hemopexin domains of MMP9 as a therapeutic strategy for osteoclast inhibition

Pasternak D, Ohayon S, Levaot N, Papo N. New Biotechnology journal 2026

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PRSS23 promotes ovarian cancer peritoneal dissemination independent of protease activity

Akhtar S, Coban M, Miller E,  Hockla A, Maina E,  Mehner C, Ilic S, Papo N, Radisky D,  Radisky E. Journal of Biological Chemistry 2026 

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2025

Modifying inhibitor specificity for homologous enzymes by machine learning

Gozlan D, Meiri R, Shapira G, Coban M, Radisky E, Orenstein Y, Papo N. The FEBS journal 2025

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Neuroprotective functions of the APPI domain of amyloid precursor protein (APP): Reducing KLK6-mediated APP cleavage and Aβ42 formation and aggregation

Lacham-Hartman S, Oren O, Rabinovitch M, & Papo N. International Journal of Biological Macromolecules 2025

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Structural analysis of nanobody interactions with their prostate-specific membrane antigen binding epitopes

Alon-Zchut, G., Zalk, R., Huynh, T. T., Zalutsky, M. R., Weizmann, Y., Zarivach, R., & Papo, N. International Journal of Biological Macromolecules 2025

2024

Preventing osteoporotic bone loss in mice by promoting balanced bone remodeling through M-CSFRGD, a dual antagonist to c-FMS and αvβ3 receptors

Yuval Zur Y, Katchkovsky S, Itzhar A, Abramovitch-Dahan C, Stepensky D, Papo N & levaot N. International Journal of Biological Macromolecules 2024​​

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Mapping the sclerostin–LRP4 binding interface identifies critical interaction hotspots in loops 1 and 3 of sclerostin​

Katchkovsky S, Meiri R, Lacham-Hartman S, Orenstein Y, Levaot N & Papo N. FEBS Letters 2024 

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Deep neural networks for predicting the affinity landscape of protein-protein interactions 

Meiri R, Lotati S. L. A, Orenstein Y & Papo N. iScience 2024

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PSMA-reactive NB7 single domain antibody fragment: A potential scaffold for developing prostate cancer theranostics

Huynh T T, Feng Y, Meshaw R, Zhao X G, Rosenfeld L, Vaidyanathan G, Papo N & Zalutsky M R. Nuclear medicine and biology 2024

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2023

Potent inhibition of MMP-9 by a novel sustained-release platform attenuates left ventricular remodeling following myocardial infarction

Itzhar A, Yosef G, Eilon-Ashkenazy M, Shmidov Y, Gil H, Lacham-Hartman S, Elyagon S, Etzion S, Bitton R, Cohen S, Etzion Y & Papo N. Journal of Controlled Release (JCR). 2023

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Serine protease inhibitors decrease metastasis in prostate, breast and ovarian cancers

Sananes A, Cohen I, Allon I, Ben-David O, Shareb RA, Yegodayev KM, Stepensky D, Elkabets M, Papo N. Mol Oncol. 2023

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APPI-Derived Cyclic Peptide Enhances Aβ42 Aggregation and Reduces Aβ42-Mediated Membrane Destabilization and Cytotoxicity

Lacham-Hartman S, Moshe R, Ben-Zichri S, Shmidov Y, Bitton R, Jelinek R, Papo N. ACS Chem Neurosci. 2023

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Developing a dual VEGF/PDL1 inhibitor based on high-affinity scFv heterodimers as an anti-cancer therapeutic strategy

Tzuri, N., Yegodayev, K. M., Elkabets, M., Aharoni, A., & Papo, N. Scientific Reports. 2023

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Utilizing genetic code expansion to modify N-TIMP2 specificity towards MMP-2, MMP-9, and MMP-14

Hayun H, Coban M, Bhagat A. K, Ozer E, Alfonta L, Caulfield T. R, Radisky ES & Papo N. Scientific Reports. 2023

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2022

Synergistic Activity of Anticancer Polyphenols Embedded in Amphiphilic Dendrimer Nanoparticles

Ben-Zichri S, Meltzer M, Lacham-Hartman S, Kolusheva S, Hadad U, Papo N, and Jelinek R. ACS Appl. Polym. Mater. 2022

Yeast‐based directed‐evolution for high‐throughput structural stabilization of G protein‐coupled receptors (GPCRs)

Meltzer M, Zvagelsky T, Hadad U, Papo N & Engel S. Scientific Reports. 2022

In vitro inhibition of cancer angiogenesis and migration by a nanobody that targets the orphan receptor Tie1

Meltzer M, Eliash N,  Azoulay Z, Hadad U, Papo N. Cellular and Molecular Life Sciences. 2022

Bioorthogonal PEGylation Prolongs the Elimination Half-Life of N-TIMP2 While Retaining MMP Inhibition

Hayun H, Arkadash V, Sananes A, Arbely E, Stepensky D, and Papo N. Bioconjugate Chem. 2022

Modifying pH-sensitive PCSK9/LDLR interactions as a strategy to enhance hepatic cell uptake of low-density lipoprotein cholesterol (LDL-C)

Ben-Naim L, Khalaila I, and Papo N. Protein Engineering, Design and Selection. 2022

Competitive blocking of LRP4-sclerostin binding interface strongly promotes bone anabolic functions

Katchkovsky S, Chatterjee B, Abramovitch-Dahan C, Papo N, Levaot N. Cell Mol Life Sci. 2022

2021

Avidity observed between a bivalent inhibitor and an enzyme monomer with a single active site

Lacham-Hartman S, Shmidov Y, Radisky ES, Bitton R, Lukatsky DB, Papo N. Plos one. 2021

Bcl-2-Homology-Only Proapoptotic Peptides Modulate β-Amyloid Aggregation and Toxicity

Ben-Zichri S, Malishe R, Oren O, Bloch DN, Taube R, Papo N, Jelinek R. ACS Chem. Neurosci. 2021

Amyloid β structural polymorphism, associated toxicity and therapeutic strategies

Oren O, Taube R, Papo N,  Cell Mol Life Sci​.  2021

Climbing Up and Down Binding Landscapes through Deep Mutational Scanning of Three Homologous Protein–Protein Complexes.

Heyne M, Shirian J, Cohen I, Peleg Y, Radisky ES, Papo N, Shifman JM. J Am Chem Soc. 2021

Kallikrein-Related Peptidase 6 Is Associated with the Tumour Microenvironment of Pancreatic Ductal Adenocarcinoma.

Candido JB, Maiques O, Boxberg M, Kast V, Peerani E, Tomás-Bort E, Weichert W, Sananes A, Papo N, Magdolen V, Sanz-Moreno V, Loessner D. Cancers. 2021

A KLK4 proteinase substrate capture approach to antagonize PAR1.

Rabinovitch E, Mihara K, Sananes A, Zaretsky M, Heyne M, Shifman J, Aharoni A, Hollenberg MD, Papo N. Sci Rep. 2021

Predicting mutant outcome by combining deep mutational scanning and machine learning.

Sarfati H, Naftaly S, Papo N, Keasar C. Proteins. 2021 

A Mechanism for the Inhibition of Tau Neurotoxicity: Studies with Artificial Membranes, Isolated Mitochondria, and Intact Cells.

Naveh Tassa S, Ben Zichri S, Lacham-Hartman S, Oren O, Slobodnik Z, Eremenko E, Toiber D, Jelinek R, Papo N. ACS Chem Neurosci. 2021

Simultaneous targeting of CD44 and MMP9 catalytic and hemopexin domains as a therapeutic strategy.

Yosef G, Hayun H, Papo N. Biochem J. 2021

The pro-apoptotic domain of BIM protein forms toxic amyloid fibrils.

Malishev R, Ben-Zichri S, Oren O, Shauloff N, Peretz T, Taube R, Papo N, Jelinek R. Cell Mol Life Sci. 2021 

2020

Engineering Stem Cell Factor Ligands with Different c-Kit Agonistic Potencies.

Tilayov T, Hingaly T, Greenshpan Y, Cohen S, Akabayov B, Gazit R, Papo N. Molecules. 2020.

Nanobodies Targeting Prostate-Specific Membrane Antigen for the Imaging and Therapy of Prostate Cancer.

Rosenfeld L, Sananes A, Zur Y, Cohen S, Dhara K, Gelkop S, Ben Zeev E, Shahar A, Lobel L, Akabayov B, Arbely E, Papo N. J Med Chem. 2020

Quantitative mapping of binding specificity landscapes for homologous targets by using a high-throughput method.

Aharon L, Aharoni SL, Radisky ES, Papo N. Biochem J. 2020 

Aβ42 Double Mutant Inhibits Aβ42-Induced Plasma and Mitochondrial Membrane Disruption in Artificial Membranes, Isolated Organs, and Intact cells.

Oren O, Ben Zichri S, Taube R, Jelinek R, Papo N. ACS Chem Neurosci. 2020.

Generating quantitative binding landscapes through fractional binding selections combined with deep sequencing and data normalization.

Heyne M, Papo N, Shifman JM. Nat Commun. 2020.

2019

A hyperthermophilic protein G variant engineered via directed evolution prevents the formation of toxic SOD1 oligomers.

Dagan B, Oren O, Banerjee V, Taube R, Papo N. Proteins. 2019. 

PRSS3/Mesotrypsin and kallikrein-related peptidase 5 are associated with poor prognosis and contribute to tumor cell invasion and growth in lung adenocarcinoma.

Ma H, Hockla A, Mehner C, Coban M, Papo N, Radisky DC, Radisky ES. Sci Rep. 2019.

Disulfide engineering of human Kunitz-type serine protease inhibitors enhances proteolytic stability and target affinity toward mesotrypsin.

Cohen I, Coban M, Shahar A, Sankaran B, Hockla A, Lacham S, Caulfield TR, Radisky ES, Papo N. J Biol Chem. 2019.

Residue-level determinants of angiopoietin-2 interactions with its receptor Tie2.

Bakhman A, Rabinovich E, Shlamkovich T, Papo N, Kosloff M. Proteins. 2019.

An Engineered Variant of the B1 Domain of Protein G Suppresses the Aggregation and Toxicity of Intra- and Extracellular Aβ42.

Banerjee V, Oren O, Dagan B, Taube R, Engel S, Papo N. ACS Chem Neurosci. 2019.

2018

Mapping protein selectivity landscapes using multi-target selective screening and next-generation sequencing of combinatorial libraries.

Naftaly S, Cohen I, Shahar A, Hockla A, Radisky ES, Papo N. Nat Commun. 2018.

An Aβ42 variant that inhibits intra- and extracellular amyloid aggregation and enhances cell viability.

Oren O, Banerjee V, Taube R, Papo N. Biochem J. 2018.

Depsipeptides Featuring a Neutral P1 Are Potent Inhibitors of Kallikrein-Related Peptidase 6 with On-Target Cellular Activity.

De Vita E, Schüler P, Lovell S, Lohbeck J, Kullmann S, Rabinovich E, Sananes A, Heßling B, Hamon V, Papo N, Hess J, Tate EW, Gunkel N, Miller AK. J Med Chem. 2018. 

Combinatorial engineering of N-TIMP2 variants that selectively inhibit MMP9 and MMP14 function in the cell.

Arkadash V, Radisky ES, Papo N. Oncotarget. 2018.

A dual-specific macrophage colony-stimulating factor antagonist of c-FMS and αvβ3 integrin for osteoporosis therapy.

Zur Y, Rosenfeld L, Keshelman CA, Dalal N, Guterman-Ram G, Orenbuch A, Einav Y, Levaot N, Papo N. PLoS Biol. 2018.

Targeting the Tie2-αvβ3 integrin axis with bi-specific reagents for the inhibition of angiogenesis.

Shlamkovich T, Aharon L, Koslawsky D, Einav Y, Papo N. BMC Biol. 2018.

Targeting the MMP-14/MMP-2/integrin alpha(v)beta(3) axis with multispecific N-TIMP2-based antagonists for cancer therapy.

Yosef G, Arkadash V, Papo N. J Biol Chem. 2018.

A bi-specific inhibitor targeting IL-17A and MMP-9 reduces invasion and motility in MDA-MB-231 cells.

Koslawsky D, Zaretsky M, Alcalay R, Mazor O, Aharoni A, Papo N. Oncotarget. 2018.

A potent, proteolysis-resistant inhibitor of kallikrein-related peptidase 6 (KLK6) for cancer therapy, developed by combinatorial engineering.

Sananes A, Cohen I, Shahar A, Hockla A, De Vita E, Miller AK, Radisky ES, Papo N. J Biol Chem. 2018.

Pre-equilibrium competitive library screening for tuning inhibitor association rate and specificity toward serine proteases.

Cohen I, Naftaly S, Ben-Zeev E, Hockla A, Radisky ES, Papo N. Biochem J. 2018.

Converting a broad matrix metalloproteinase family inhibitor into a specific inhibitor of MMP-9 and MMP-14.

Shirian J, Arkadash V, Cohen I, Sapir T, Radisky ES, Papo N, Shifman JM. FEBS Lett. 2018.

MIF inhibits the formation and toxicity of misfolded SOD1 amyloid aggregates: implications for familial ALS.

Shvil N, Banerjee V, Zoltsman G, Shani T, Kahn J, Abu-Hamad S, Papo N, Engel S, Bernhagen J, Israelson A. Cell Death Dis. 2018.

2017

A computational combinatorial approach identifies a protein inhibitor of superoxide dismutase 1 misfolding, aggregation, and cytotoxicity.

Banerjee V, Oren O, Ben-Zeev E, Taube R, Engel S, Papo N. J Biol Chem. 2017.

Engineering a monomeric variant of macrophage colony-stimulating factor (M-CSF) that antagonizes the c-FMS receptor.

Zur Y, Rosenfeld L, Bakhman A, Ilic S, Hayun H, Shahar A, Akabayov B, Kosloff M, Levaot N, Papo N. Biochem J. 2017.

Utilizing combinatorial engineering to develop Tie2 targeting antagonistic angiopoetin-2 ligands as candidates for anti-angiogenesis therapy.

Shlamkovich T, Aharon L, Barton WA, Papo N. Oncotarget. 2017.

Editorial overview: Engineering and design: New trends in designer proteins.

Shifman JM, Papo N. Curr Opin Struct Biol. 2017.

Development of High Affinity and High Specificity Inhibitors of Matrix Metalloproteinase 14 through Computational Design and Directed Evolution.

 Arkadash V, Yosef G, Shirian J, Cohen I, Horev Y, Grossman M, Sagi I, Radisky ES, Shifman JM, Papo N. J Biol Chem. 2017.

Constitutive Association of Tie1 and Tie2 with Endothelial Integrins is Functionally Modulated by Angiopoietin-1 and Fibronectin.

Dalton AC, Shlamkovitch T, Papo N, Barton WA. PLoS One. 2017.

Engineered ligand-based VEGFR antagonists with increased receptor binding affinity more effectively inhibit angiogenesis.

Kapur S, Silverman AP, Ye AZ, Papo N, Jindal D, Blumenkranz MS, Cochran JR. Bioeng Transl Med. 2017.

2016

Identifying Residues that Determine SCF Molecular-Level Interactions through a Combination of Experimental and In silico Analyses.

Rabinovich E, Heyne M, Bakhman A, Kosloff M, Shifman JM, Papo N. J Mol Biol. 2017.

An Acrobatic Substrate Metamorphosis Reveals a Requirement for Substrate Conformational Dynamics in Trypsin Proteolysis.

Kayode O, Wang R, Pendlebury DF, Cohen I, Henin RD, Hockla A, Soares AS, Papo N, Caulfield TR, Radisky ES. J Biol Chem. 2016.

Constitutive Association of Tie1 and Tie2 with Endothelial Integrins is Functionally Modulated by Angiopoietin-1 and Fibronectin.

Dalton AC, Shlamkovitch T, Papo N, Barton WA. PLoS One. 2016.

Superoxide Dismutase 1 (SOD1)-Derived Peptide Inhibits Amyloid Aggregation of Familial Amyotrophic Lateral Sclerosis SOD1 mutants.

Banerjee V, Shani T, Katzman B, Vyazmensky M, Papo N, Israelson A, Engel S. ACS Chem Neurosci. 2016.

Protein Engineering by Combined Computational and In Vitro Evolution Approaches.

Rosenfeld L, Heyne M, Shifman JM, Papo N. Trends Biochem Sci. 2016.

Combinatorial protein engineering of proteolytically resistant mesotrypsin inhibitors as candidates for cancer therapy.

Cohen I, Kayode O, Hockla A, Sankaran B, Radisky DC, Radisky ES, Papo N. Biochem J. 2016.

2005

Yosef Rosenfeld, Niv Papo, and Yechiel Shai. J Biol Chem. 2005.

Endotoxin (Lipopolysaccharide) Neutralization by Innate Immunity Host-Defense Peptides.

Utilizing ESEEM Spectroscopy to Locate the Position of Specific Regions of Membrane-Active Peptides within Model Membranes

Raanan Carmieli, Niv Papo,y Herbert Zimmermann,z Alexey Potapov, Yechiel Shai,y and Daniella Goldfarb. Biophysical Journal. 2005

Mechanistic and Functional Studies of the Interaction of a Proline-rich Antimicrobial Peptide with Mammalian Cells.

Linda Tomasinsig, Barbara Skerlavaj, Niv Papo, Barbara Giabbai, Yechiel Shai, and Margherita Zanetti. JBC. 2005.

Host defense peptides as new weapons in cancer treatment.

Papo N, Shai Y. Cell Mol Life Sci. 2005. 

Controlled alteration of the shape and conformational stability of α-helical cell-lytic peptides: effect on mode of action and cell specificity.

Igor  Zelezestky, Sabrina Pacor, Ulrike Pag, Niv Papo, Yechiel Shai, Hans-Georg Sahl, Alessandro Tossi. Biochem J. 2005.

A Molecular Mechanism for Lipopolysaccharide Protection of Gram-negative Bacteria from Antimicrobial Peptides.

Niv Papo and Yechiel Shai. J Biol Chem. 2005.

2004

Suppression of Human Prostate Tumor Growth in Mice by a Cytolytic D-, L-Amino Acid Peptide: Membrane Lysis, Increased Necrosis, and Inhibition of Prostate- Specific Antigen Secretion.

Niv Papo, Amir Braunstein, Zelig Eshhar, Yechiel Shai. Cancer Res. 2004.

In Vitro Activity and Potency of an Intravenously Injected Antimicrobial Peptide and Its DL Amino Acid Analog in Mice Infected with Bacteria.

Braunstein A, Papo N, Shai Y. Antimicrob Agents Chemother. 2004

Effect of Drastic Sequence Alteration and D-Amino Acid Incorporation on the Membrane Binding Behavior of Lytic Peptides.

Niv Papo , Yechiel Shai. biochemistry. 2004. 

Effects of the antimicrobial peptide temporin L on cell morphology, membrane permeability and viability of Escherichia coli.

Maria Luisa Mangoni, Niv Papo, Donatella Barra, Maurizio Simmaco, Argante Bozzi, Antonio Di Giulio, Andrea C Rinaldi. Biochem J. 2004

2003

Can we predict biological activity of antimicrobial peptides from their interactions with model phospholipid membranes?

Niv Papo, Yechiel Shai. Peptides. 2003.

In vitro activity and mode of action of diastereomeric antimicrobial peptides against bacterial clinical isolates.

Pag U, Oedenkoven M, Papo N, Oren Z, Shai Y, Sahl HG. J Antimicrob Chemother. 2004.

Ranacyclins, a New Family of Short Cyclic Antimicrobial Peptides: Biological Function, Mode of Action, and Parameters Involved in Target Specificity.

M. Luisa Mangoni, Niv Papo,Giuseppina Mignogna, David Andreu, Yechiel Shai, Donatella Barra and Maurizio Simmaco. Biochemisty. 2003.

New Lytic Peptides Based on the D,L-Amphipathic Helix Motif Preferentially Kill Tumor Cells Compared to Normal Cells

Niv Papo and Yechiel Shai. Biochemisty. 2003.

A Novel Lytic Peptide Composed of DL-Amino Acids Selectively Kills Cancer Cells in Culture and in Mice.

Papo N, Shahar M, Eisenbach L, Shai Y.  J Biol Chem. 2003.

Exploring Peptide Membrane Interaction Using Surface Plasmon Resonance: Differentiation between Pore Formation versus Membrane Disruption by Lytic Peptides.

Niv Papo and Yechiel Shai. Biochemistry. 2002.

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