PAPO LAB
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PROF. NIV PAPO
Prof. Papo develops high affinity proteins, using a combination of experimental and computational methodologies, to bind to and antagonize a variety of disease-related targets. He engineers novel proteins through both random and rational approaches to improve their selectivity such that they more specifically target receptors that are overexpressed in disease states but expressed at normal levels in healthy cells.
In doing so, his lab generates novel biotherapeutics and enhanced imaging agents.
STUDENTS
SHIRAN LACHAM
PhD Student
In her studies, Shiran maps the molecular interactions of APPI and derived peptide with Aβ42 to identify specific binding epitopes in APPI. Shiran also studies the inhibition effect of APPI on the proteolytic the activity of KLK6-dependent Aβ42 formation to elucidate their mode of action in Alzheimer disease. In a different project, Shiran determines affinity and specificity advantages conferred through trypsin inhibitor (APPI) polyvalency.
In targeting trypsin-like proteases, Shiran’s data indicate that dimeric trypsin inhibitors capable of simultaneously targeting two trypsin molecules show significant affinity enhancement relative to monomeric inhibitors.
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STEFAN LLIC
Post Doctoral Fellow
In his studies, Stefan is targeting novel protease PRSS23 to inhibit ovarian cancer progression. Specifically, Stefan aims to define the enzymatic activity and determine the structure of PRSS23. In a different project, Stefan is developing high affinity peptide binders to subunit 3 (apical domain) of the yeast chaperonin CCT/TRiC, which has 8 different subunits that most likely have different substrate specificities, but they are not known.
SVETLANA KATCHKOVSKY
Post Doctoral Fellow
in collaboration with Noam Levaot, BGU
Sveta demonstrates that SclN93A competes with wild-type Scl (Scl) for a common binding site on LRP4 and antagonizes Scl inhibition of the Wnt signaling pathway in osteoblasts in vitro. Sveta also demonstrates that two weeks of bi-weekly subcutaneous injections of SclN93A fused to the fragment crystallizable (Fc) domain of immunoglobulin (SclN93AFc), which retains the antagonistic activity of the mutant, significantly increases bone formation rate and enhances trabecular volumetric bone fraction, trabecular number, and bone length in developing mice. These studies further provide evidence that compounds that inhibit Scl–LRP4 interactions offer a potential strategy to promote anabolic bone functions.
OZ REUVENI
MSc Student (Meitar program)
Oz develops a normalization approach to convert next generation sequencing results (obtained from protein library affinity sorts) to Ki (protease inhibition constants) values, and tests the approach on a held-out test set of APPI mutants complexed with mesotrypsin and KLK6. The approach is based on a deep neural network (developed in the lab) to predict the distribution through the APPI library affinity and selectivity sorting gates, and then converting the predicted distribution by a learned normalization formula to a single Ki value.
NOAM TZURI
PhD Student
In her studies, Noam is developing dual VEGF/PDL1 inhibitors based on high-affinity scFv heterodimers as a therapeutic strategy. Specifically, this kind of a structure that consists of two scFv targeting VEGF and PDL1, followed by Fc is developed by Noam as a novel strategy for cancer therapy.
SHIR EDEN
MSc Student (Meitar program)
Shir is focused on developing nanobodies (Nbs), derived from camel, against Receptor Tyrosine Kinases HER2/HER3 heterodimer, function as an oncogenic unit and initiate signaling pathways to promote tumor cell survival, by forming a heterodimer through interactions between their extracellular dimerization arms, TM, and c-terminal domains. In a previous project in the lab, we have optimized a method for efficient screening, identification and purification of conformation-sensitive Nbs for the detection of HER2/HER3 proteins in their native conformation expressed on the surface of cells. Shir is currently testing the most potent NBs in cellular and pre-clinical models of different types of cancer.
GILI SHAPIRA
MSc Student (Meitar program)
Gili’s project is directed towards engineering novel inhibitors for well-established chemical targets in cancer therapy - Matrix Metalloproteinases (MMPs). MMPs are large family of enzymes whose abnormal activities have been implicated in cancer progression. Despite extensive efforts in the field, and due to MMPs similar structures, there are currently no clinically approved therapeutic agents that are specific for MMPs. In her studies, Gili proposes to create and test the therapeutic efficacy of mono- and bispecific proteins that can selectively bind and inhibit the action of a single or multiple selected MMPs.
Yuval Pinkert
MSc Student
Yuval project focuses on targeting kallikrein-related protease 6 (KLK6) and matrix metalloproteinase-9 (MMP9) simultaneously with a new class of protein-based inhibitor for the treatment of cancer. The dual specific inhibitor is derived from tissue inhibitors ofmetalloproteinase-2 (N-TIMP2) which is a natural inhibitor of MMP9 combined with a synthetic small molecule inhibitor of KLK6 (SIKL). The conjugation of the two inhibitors is done by using the properties of non-canonical amino acid and click chemistry reaction.
REUT MOSHE
MSc Student
in collaboration with Yaron Orenstein, BIU
Reut maps binding specificity landscapes of human Kunitz domains toward engineering isoform-selective trypsin inhibitors. In a different project, Reut generates aggregation landscapes of Aβ42 toward engineering Aβ42 aggregation inhibitors. Reut is also identifying affinity enhancing mutations in an inhibitor-protease complex using mutant library screening and next generation sequencing. Reut accomplishes these tasks by integrating yeast surface display (YSD) combinatorial library screening with next-generation sequencing (NGS) and machine-learning (ML) approaches.
YIHEA LAFI
Ph.D direct track program
Yihea's project , try to find a novel nanobody that targets the transferrin receptor ,a special receptor that imports iron to the brain by internalizing the transferrin-iron complex through receptor-mediated endocytosis . He is aiming to take advantage from this using our lab technique (yeast surface display ) to found a drug delivery approach based unique nanobody for crossing the blood brain barrier (BBB).
FERAS JABAREEN
MSc Student
Feras studies the compatibility of Aβ42DM, previously developed in the lab as an Aβ42 aggregation inhibitor, with buffers that would be usable in mouse model of Alzheimer's disease (5XFAD). By attaching osmotic pumps with a sustained release system to the mouse brain, we plan to study the effectiveness of Aβ42DM in preventing Aβ42 aggregation and toxicity in pre-clinical models of Alzheimer's disease.
DAN PASTERNAK
MSc Student (Meitar program)
Dan's project is examination in different aspects of the multi-specific inhibitor C9-PEX, which binds CD44 and MMP-9 targets simultaneously on osteoclasts, as a potential therapeutic
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YANIV DEBUTTON
MSc Student (Meitar program)
Yaniv's project is focusing on incorporating non-canonical amino acids (ncAAs) into nanobodies (Nbs) for conjugation of a cleavable cytotoxic agent via a click chemical reactionto generate nanobody-drug conjugates (NDCs). Based on our analysis of different positions on the Nb's structure, we were able to determine a few optimal locations that would not compromise its folding and function. In an effort to overcome in-vivo kidney retention issues resulting from the presence of an His-tag in the Nb sequence, the latter are prepared with protease-cleaved His-tag and/or C-tag used for purification.
GAL ALON
MSc Student (Meitar program)
in collaboration with Yossi Weizmann, BGU
Gal hypothesize that by conjugating between gold nanoparticles and a nanobody (NB), we could identify in an unambiguous way the nature of the binding of the NB to the native PSMA expressed on cancer cells. The gold nanoparticles will enable an easier identification of the NB-PSMA binding on the membrane of prostate cancer (PCa) cells in Cryo-EM, since they willlabel the PSMA protein and distinguish it from other membrane proteins.
AMIT EISENBERG
MSc Student
in collaboration with Tomer Cooks, BGU
Amit research is about creating a combination modality for prostate cancer treatment. Previous experiments have shown that DaRT (radiation therapy) is not beneficial enough to fully cure the primary tumor and metastasis. For that reason, we are combining the DaRT with a nanobody-small molecule conjugate for the superior treatment of prostate cancer.
FORMER STUDENTS
LITAL BEN NAIM
PhD Student 2020
PhD Thesis: Developing proteins and nanobodies as conformation-specific inhibitors.
Today:
Postdoc fellow at the department of Radiology at Harvard Medical School and Massachusetts General Hospital
GAL YOSEF
PhD Student 2020
PhD Thesis: "Engineering bi-specific inhibitors for matrix metalloproteinasas"
Today:
Scientist at JAMM therapeutics
LIOR ROSENFELD
PhD Student 2020
PhD Thesis: Using combinatorial methods to study protein-protein interactions and generate new ones for developing protein-based therapies and diagnostics.
Today:
Molecular Biologist at Ukko
SHAY-LEE AHARONI LOTATI
MSc Student 2020
Master Thesis: "Identifying affinity enhancing mutations in an inhibitor-protease complex using mutant library screening and next generation sequencing"
Today:
PhD student at Weizmann Institute of Science
HEZI HAYUN
PhD Student 2021
PhD Thesis: "Bioorthogonal chemistry for improving the pharmacokinetic properties and inhibitory activity of N-TIMP2"
Today:
Scientist at Aleph Farms
AMIRAM SANANES
PhD Student 2021
PhD Thesis: "A potent, proteolysis-resistant inhibitor of kallikrein-related peptidase 6 (KLK6) for cancer therapy, developed by combinatorial engineering"
Today:
Scientific analyst at Medison Ventures
MAY MELTZER
PhD Student 2021
PhD Thesis: "Directed evolution to engineer improved proteins for structural studies and drug discovery"
Today:
R&D scientist at 1E Therapeutics
Oshrit Shalev PhD
Previous Lab Manger
MAAYAN EILON ASHKENAZY
MSc Student 2019
MSc Thesis : "Designing a sustained-release system for myocardial infarction treatment."
Today:
PhD student at Weizmann Institute of Science
AMIT ITZHAR
MSc Student 2022
MSc Thesis : "Development of a potent sustained-release MMP-9 inhibitory system agains left ventricular remodeling post-myocardial infarction."
Today:
open to hiring
ZIV AZOULAY
Post Doctoral Fellow 2022
Conjugating a small molecule agent to an anti HER2 nanobody for therapy of breast cancer.
SEGEV NAVE
MSc Student 2020
Master Thesis: "A Mechanism for the Inhibition of Tau Neurotoxicity: Studies with Artificial Membranes, Isolated Mitochondria, and Intact Cells."
Today:
PhD student at Weizmann Institute of Science
LIDAN AHARON
MSc Student 2018
MSc Thesis : "Quantitative mapping of binding specificity landscapes for homologous targets by using a high-throughput method"
Today:
Java Developer & Scrum Master at the bank's revolutionary modernization project
NOAM ELIASH
MSc Student 2019
MSc Thesis: "Engineering high affinity binders for orphan receptors:
a nanobody-Tie1 complex as a case study."
Today:
Research And Development Engineer at Aummune
SI NAFTALY
MSc Student 2017
MSc Thesis: "Mapping protein specificity landscapes using a combination of multi-target selective screening and next-generation sequencing of combinatorial libraries"
Today:
Molecular biologist at Ukko
EITAN RABINOVICH
PhD Student 2019
PhD Thesis: "Using in vitro evolution approaches for the mapping of SCF binding epitopes and the design of novel binders and inhibitors for PAR1"
Today:
Molecular Biologist at at Ukko
VALERIA ARKADASH
PhD Student 2018
PhD Thesis: "Developing an inhibitor for Matrix Metalloprotease (MMP)-14 and MMP-9 based on the N- terminal domain of the natural inhibitor TIMP2, for cancer treatment"
Today:
Research associate in the department of Structural Biology at the Weizmann Institute of Science.
OFEK OREN
PhD Student 2020
PhD Thesis : "Protein engineering in mammalian cells- developing novel inhibitors for amyloids aggregation"
Today:
Researcher at Aleph farms
DANA KOSLAWSKY
MSc Student 2017
Master Thesis: "A bi-specific inhibitor targeting IL-17A and MMP-9 reduces invasion and motility in MDA-MB-231 cells".
Today:
Data Scientist at Anodot
TAL HINGALY
MSc student 2014
Master thesis: "Engineering antagonistic Cytokine Stem Cell Factor variants to provide a new therapeutic mechanism for cancer"
Today:
Works at TEVA
ITAY COHEN
PhD Student 2018
PhD Thesis: "Combinatorial engineering of proteolytically resistant APPI variants that inhibit human mesotrypsin for cancer therapy."
Today:
Works at TEVA
TAL TILAYOV
MSc student 2016
Master thesis: "Engineering antagonistic Cytokine Stem Cell Factor variants to provide a new therapeutic mechanism for cancer."
YUVAL HOREV
MSc Student 2018
Mater thesis: "Developing protein bispecific heterodimers to antagonize MT1-MMP and MMP2 for cancer therapy."
Today:
PhD student at the Technion – Israel Institute of Technology
BAR DAGAN
MSc Student 2018
Master Thesis: "Design of SOD1 Amyloid inhibitors by combinatorial methods"
MICHAEL HEYNE
PhD Student 2018
PhD Thesis: "Utilizing computational and experimental approaches to study APPI-Mesotrypsin and BPTI-trypsin binding interactions in residue-level resolution"
Today:
Works as International Application Specialist at Hamilton Bonaduz AG
TOMER SHLAMKOVITCH
PhD Student 2018
PhD Thesis : "Developing new generation of angiopoietin-2 derived Tie2 antagonists for cancer imaging and therapy."
Today:
Director of Antibody Engineering at Biolojic Design, Ltd.
YUVAL ZUR
PhD Student 2019
PhD Thesis: "Developing bi-specific M-CSF-based antagonists against c-fms and αVβ3 integrin."
Today:
Molecular Biology Scientist at Cytonus Therapeutics Inc. USA
VICTOR BANERJEE
Post Doctoral Fellow 2018
Design of Amyloid inhibitors by directed evolution: Target Multiple Amyloidogenic Proteinsץ
Today:
Works as a postdoctoral researcher at Prof. Claudio Soto's lab department of Neurology, McGovern Medical School UT health.
GALIT SHAHAF
Post Doctoral Fellow 2014
"Developing cyclotide-small molecule conjugates to antagonize MT1-MMP for cancer therapy"
HAGIT BACHMAT
PhD Student 2021
PhD Thesis : "Computational prediction of protein protein interactions (PPI) by combining NGS, energy terms and machine learning."
Today:
PhD student in computer science at BGU- Ben gurion university of the negev.
ORNA AVIDAN
Post Doctoral Fellow 2015
Targeting ErbB1/2 with Tendamistat for applications in cancer imaging and therapy.
Today:
Retired
TAMARA BIRMAN
MSc Student 2014
Master Thesis : "Using directed evolution to engineer Tendamistat variants with high affinity to PSMA for Prostate cancer diagnostics."
Today:
PhD student at the Technion – Israel Institute of Technology
Project students:
2012 – 2013 - Helly Atia, Hagar Gallea, Eitan Rabinovitch
2013 – 2014 - Gal Yosef, Shani Butbika, Anat Afek, Karin Cohen, Lior Rosenfeld
2014 – 2015 - Dana Koslowsky and Tal Tilayov
2015 – 2016 - Hagit Bachmat, Nofar Dalal, Bar Gazit
High school students
2016 – 2017 – Naama Shafir
2018 – 2019 – Roni Gliksman
2020 – current – Evyatar Azulay