NIV PAPO

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.

OSHRIT

Oshrit Shalev PhD

Laboratory technician

Oshrit is testing engineered nanobodies as prostate specific membrane antigen (PSMA) imaging and therapeutic agents in mouse models of prostate cancer. For that, Oshrit is testing the ability of labeled nanobodies to target prostate tumors in mouse models for development and use as optical and positron emission tomography (PET) imaging agents.

STUDENTS

SHIRAN

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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MAY MELTZER

PhD Student

May is developing a yeast-based directed-evolution approach for high-throughput structural stabilization of G protein-coupled receptors (GPCR). Specifically, May is working towards isolation of A2aR and ETaR variants resistant to octyl glycoside (OG), evaluation of stability properties of selected A2aR variants and performing a structural analysis of stable A2aR by X-ray crystallography. In a different project, May is engineering high affinity nanobody binders for orphan receptors and using a nanobody-Tie1 complex as a case study. In her studies, may shows that utilizing naïve, computationally designed and experimentally stabilized synthetic nanobody libraries result in the identification of well-expressed and functional nanobody variants.

ZIV

ZIV AZOULAY

Post Doctoral Fellow

Ziv is developing conformational nanobodies targeting cell membrane receptors to inhibit signaling in cancer. For that, Ziv is developing Nbs in a camel that recognize conformation-dependent epitopes on membrane protein monomers and heterodimers. These NBs serve as inhibitors by binding simultaneously to both HER2 & HER3 receptors  In addition, Ziv is developing Nbs against PAR1 that bind to its extracellular N-terminal tail or extracellular loops in order block its ligand binding and activation, and by that inhibit its signaling pathways in cancer. In a different project, Ziv is developing Aβ42 inhibitors that redirect the aggregation of Aβ42 into off-pathway non-toxic oligomers, and test them both in-vitro and in-vivo in 5XFAD mice.

AMIT

AMIT ITZHAR

MSc student

In her studies, Amit is designing a sustained-release system for myocardial infarction treatment by simply fusing HBP to a therapeutic protein. In a different project Amit is developing a a dual-specific macrophage colony stimulating factor antagonist that inhibits c-FMS and αvβ3 integrin for osteoporosis therapy and characterizing these inhibitors in terms of pharmacokinetic properties and therapeutic potency in preclinical models.

REUT

 REUT MOSHE

MSc Student

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.

HEZI

HEZI HAYUN

PhD Student

In his studies, Hezi is utilizing bioorthogonal chemistry for improving the pharmacokinetic properties and inhibitory activity of N-TIMP2. Specifically Hezi is extending N-TIMP2 circulation half-life by site-specific PEGylation and in a second project Hezi is improving N-TIMP2 inhibition potency towards MMP-14 by increasing its zinc binding affinity.

STEFAN

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.

NOAM

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.

SVETA

SVETLANA KATCHKOVSKY

PhD Student

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

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.

gili

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.

SHIR

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.

FORMER STUDENTS

lital

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

GAL YOSEF

PhD Student 2020

PhD Thesis: "Engineering bi-specific inhibitors for matrix metalloproteinasas"

Today:

Scientist at JAMM therapeutics

lior

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

sheylee

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

amiram

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

maayan

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

segev

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

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

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

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

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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

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

OFEK OREN

PhD Student 2020

PhD Thesis : "Protein engineering in mammalian cells- developing novel inhibitors for amyloids aggregation"

Today: 

Researcher at Aleph farms

DANA

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

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

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

TAL TILAYOV

MSc student 2016

Master thesis: "Engineering antagonistic Cytokine Stem Cell Factor variants to provide a new therapeutic mechanism for cancer."

yuval

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

BAR DAGAN

MSc Student 2018

Master Thesis: "Design of SOD1 Amyloid inhibitors by combinatorial methods"


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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

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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

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

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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

GALIT SHAHAF

Post Doctoral Fellow 2014

"Developing cyclotide-small molecule conjugates to antagonize MT1-MMP for cancer therapy"

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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. 

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ORNA AVIDAN

Post Doctoral Fellow 2015

Targeting ErbB1/2 with Tendamistat for applications in cancer imaging and therapy.

 

 

Today:

Retired

tamara

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