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Healthcare Integrator | transforming #digitalhealth adoption in Israel and worldwide🌎 |…
Articles by Yael
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BeWell.Haifa is looking for an outstanding individual to join our team
BeWell.Haifa is looking for an outstanding individual to join our team
By Yael Ophir
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TOOLBOX - Useful Tools for Digital Health Entrepreneurs
TOOLBOX - Useful Tools for Digital Health Entrepreneurs
By Yael Ophir
Activity
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I was delighted to meet with Tatiana Molcean, Executive Secretary of UNECE. UNECE plays a central role in supporting the implementation of #SDGs…
I was delighted to meet with Tatiana Molcean, Executive Secretary of UNECE. UNECE plays a central role in supporting the implementation of #SDGs…
Liked by Yael Ophir
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I am deeply honored to share that I have been selected as an honored listee in Who’s Who in America, a directory that recognizes individuals who have…
I am deeply honored to share that I have been selected as an honored listee in Who’s Who in America, a directory that recognizes individuals who have…
Liked by Yael Ophir
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🤩Exciting News! 🤩 We’re thrilled to announce the launch of the updated version of our Neuro-Finder 🧠, a groundbreaking tool that maps the vibrant…
🤩Exciting News! 🤩 We’re thrilled to announce the launch of the updated version of our Neuro-Finder 🧠, a groundbreaking tool that maps the vibrant…
Liked by Yael Ophir
Experience
Education
Publications
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Mapping Mental Health Innovation in Israel
C-Tech
Necessity is the mother of innovation, and the national trauma that has befallen Israel could be a catalyst for the next wave of mental health solutions from Israel.
Other authorsSee publication -
Femtech No Filters: What's Really Going on with Israeli Femtech?
HealthIL
There have been countless articles about the burgeoning Femtech scene in Israel.
Numerous innovation hubs, corporate programs, and local events have emerged in recent years to capitalize on the buzz. But this also creates a lot of noise. And like everything in healthcare innovation, it is critical to embrace the complexity and the nuance of healthcare, and femtech specifically, in order to maximize the potential of what is coming out of Israel.
This report will highlight some of…There have been countless articles about the burgeoning Femtech scene in Israel.
Numerous innovation hubs, corporate programs, and local events have emerged in recent years to capitalize on the buzz. But this also creates a lot of noise. And like everything in healthcare innovation, it is critical to embrace the complexity and the nuance of healthcare, and femtech specifically, in order to maximize the potential of what is coming out of Israel.
This report will highlight some of the key findings from the recent Israel Femtech Startup Review I wrote for HealthIL. The full report can be accessed here (link), but I wanted to share with you some key findings, to give insights for both founders and investors who are into the space.Other authorsSee publication -
Healthcare Industry 4.0 Challenges Map
HealthIL
Inventory Management in hospitals is complex with multiple stakeholders and constraints. There is no “one size fits all” solution like in inventory management practices from other sectors, and most off-the-shelf solutions are not applicable because of the high degree of customization and large number of stakeholders involved within healthcare organizations.
Inventory management in healthcare organizations have two ultimate goals that frequently overlap: Cost Containment and Improving…Inventory Management in hospitals is complex with multiple stakeholders and constraints. There is no “one size fits all” solution like in inventory management practices from other sectors, and most off-the-shelf solutions are not applicable because of the high degree of customization and large number of stakeholders involved within healthcare organizations.
Inventory management in healthcare organizations have two ultimate goals that frequently overlap: Cost Containment and Improving Care. Strong inventory management practices can improve both aspects, and both aspects need to be considered when a healthcare organization look to improve their inventory management practices.
The complexity of inventory management in healthcare organizations creates many challenges, but also offers many opportunities for technology to address the complexity.Other authorsSee publication -
Health Equity Challenges Map
HealthIL
Healthcare systems around the world face large, persistent, and growing disparities, which create significant challenges to health equity. Health inequity and inequality are experienced across many dimensions: geography, gender, socio-economic status, education, culture, race, or medical condition.
Achieving health equity means ensuring that healthcare system resources are used appropriately to give all people the same healthcare outcomes.Other authorsSee publication -
Nectin4 Is a Novel TIGIT Ligand Which Combines Checkpoint Inhibition and Tumor Specificity
J Immunother Cancer
Background
The use of checkpoint inhibitors has revolutionized cancer therapy. Unfortunately, these therapies often cause immune-related adverse effects, largely due to a lack of tumor specificity.
Methods
We stained human natural killer cells using fusion proteins composed of the extracellular portion of various tumor markers fused to the Fc portion of human IgG1, and identified Nectin4 as a novel TIGIT ligand. Next, we generated a novel Nectin4 blocking antibody and demonstrated…Background
The use of checkpoint inhibitors has revolutionized cancer therapy. Unfortunately, these therapies often cause immune-related adverse effects, largely due to a lack of tumor specificity.
Methods
We stained human natural killer cells using fusion proteins composed of the extracellular portion of various tumor markers fused to the Fc portion of human IgG1, and identified Nectin4 as a novel TIGIT ligand. Next, we generated a novel Nectin4 blocking antibody and demonstrated its efficacy as a checkpoint inhibitor in killing assays and in vivo.
Results
We identify Nectin4 to be a novel ligand of TIGIT. We showed that, as opposed to all other known TIGIT ligands, which bind also additional receptors, Nectin4 interacts only with TIGIT. We show that the TIGIT-Nectin4 interaction inhibits natural killer cell activity, a critical part of the innate immune response. Finally, we developed blocking Nectin4 antibodies and demonstrated that they enhance tumor killing in vitro and in vivo.
Conclusion
We discovered that Nectin4 is a novel ligand for TIGIT and demonstrated that specific antibodies against it enhance tumor cell killing in vitro and in vivo. Since Nectin4 is expressed almost exclusively on tumor cells, our Nectin4-blocking antibodies represent a combination of cancer specificity and immune checkpoint activity, which may prove more effective and safe for cancer immunotherapy.Other authorsSee publication -
Insights from 1,000 Challenges Identified in the Israeli Health System
HealthIL
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HNRNPR Regulates the Expression of Classical and Nonclassical MHC Class I Proteins.
J Immunol.
MHC class I molecules, in addition to their role in specific activation of the CTL of adaptive immune system, function also as the main ligands for NK cell inhibitory receptors, which prevent NK cells from killing normal, healthy cells. MHC class I proteins are divided into classical and nonclassical proteins. The former group consists of hundreds of HLA-A, B, and C alleles, which are universally expressed, whereas several alleles of the latter group, such as HLA-G, manifest a restricted…
MHC class I molecules, in addition to their role in specific activation of the CTL of adaptive immune system, function also as the main ligands for NK cell inhibitory receptors, which prevent NK cells from killing normal, healthy cells. MHC class I proteins are divided into classical and nonclassical proteins. The former group consists of hundreds of HLA-A, B, and C alleles, which are universally expressed, whereas several alleles of the latter group, such as HLA-G, manifest a restricted expression pattern. Despite the important role played by these molecules in innate and adaptive immune responses, their complex expression regulation is not fully known. In our study, we investigated the regulation processes controlling the expression of MHC class I molecules, with a particular focus on their 3' untranslated regions. We identified heterogeneous nuclear ribonucleoprotein R (HNRNPR) as an important positive regulator of classical and nonclassical MHC class I molecules. HNRNPR is a RNA-binding protein belonging to the heterogeneous nuclear ribonucleoprotein family, which has a known role in processing of precursor mRNA. We demonstrated that HNRNPR binds MHC class I mRNAs in their 3' untranslated regions and enhances their stability and consequently their expression. Furthermore, regulation by HNRNPR modulates the cytotoxic activity of NK cells. In conclusion, we show that HNRNPR acts as a general positive regulator of MHC class I expression.
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PILRα binds an unknown receptor expressed primarily on CD56bright and decidual-NK cells and activates NK cell functions
Oncotarget
Natural Killer (NK) cells are innate immune lymphocytes specializing in recognition and killing of tumors and pathogens, using an array of activating and inhibitory receptors. NK inhibition is mediated by a large repertoire of inhibitory receptors, whereas a limited number of activating NK cell receptors execute NK cell activation. The ligands recognized by the activating receptors are stress-induced, pathogen derived, tumor specific and even self ligands. However, the full spectrum of NK cell…
Natural Killer (NK) cells are innate immune lymphocytes specializing in recognition and killing of tumors and pathogens, using an array of activating and inhibitory receptors. NK inhibition is mediated by a large repertoire of inhibitory receptors, whereas a limited number of activating NK cell receptors execute NK cell activation. The ligands recognized by the activating receptors are stress-induced, pathogen derived, tumor specific and even self ligands. However, the full spectrum of NK cell receptors and ligands that control NK cell activity remains uncharacterized. Here we demonstrate that Paired Ig-Like type 2 Receptor Alpha (PILRα), binds a distinct human NK cell sub-population present in the peripheral blood and also in the decidua. We further demonstrate that the interaction of NK cells with PILRα expressing targets lead to elevated IFNγ secretion and cytotoxicity. In conclusion, we present here a novel NK activating ligand which binds and activates an unknown NK receptor expressed on a unique NK cell subset.
Other authorsSee publication -
Downregulation of the stress-induced ligand ULBP1 following SV40 infection confers viral evasion from NK cell cytotoxicity
Oncotarget
Polyomaviruses are a diverse family of viruses which are prevalent in the human population. However, the interactions of these viruses with the immune system are not well characterized. We have previously shown that two human polyomaviruses, JC and BK, use an identical microRNA to evade immune attack by Natural Killer (NK) cells. We showed that this viral microRNA suppresses ULBP3 expression, a stress induced ligand for the killer receptor NKG2D. Here we show that Simian Virus 40 (SV40) also…
Polyomaviruses are a diverse family of viruses which are prevalent in the human population. However, the interactions of these viruses with the immune system are not well characterized. We have previously shown that two human polyomaviruses, JC and BK, use an identical microRNA to evade immune attack by Natural Killer (NK) cells. We showed that this viral microRNA suppresses ULBP3 expression, a stress induced ligand for the killer receptor NKG2D. Here we show that Simian Virus 40 (SV40) also evades NK cell attack through the down regulation of another stress-induced ligand of NKG2D, ULBP1. These findings indicate that NK cells play an essential role in fighting polyomavirus infections and further emphasize the importance of various members of the ULBP family in controlling polyomavirus infection.
Other authors -
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The human 2B4 and NTB-A receptors bind the influenza viral hemagglutinin and co-stimulate NK cell cytotoxicity
Oncotarget
Natural Killer (NK) cells are critical in the defense against viruses in general and against influenza in particular. We previously demonstrated that the activating NK cell receptor NKp46 is involved in the killing of influenza-virus infected cells through its interaction with viral hemagglutinin (HA). Furthermore, the recognition by NKp46 and consequent elimination of influenza infected cells were determined to be sialic-acid dependent. Here, we show that the human co-activating receptors 2B4…
Natural Killer (NK) cells are critical in the defense against viruses in general and against influenza in particular. We previously demonstrated that the activating NK cell receptor NKp46 is involved in the killing of influenza-virus infected cells through its interaction with viral hemagglutinin (HA). Furthermore, the recognition by NKp46 and consequent elimination of influenza infected cells were determined to be sialic-acid dependent. Here, we show that the human co-activating receptors 2B4 and NTB-A directly recognize the viral HA protein and co-stimulate killing by NK cells. We demonstrate that the 2B4/NTB-A-HA interactions require the sialylation of these receptors, and we identified the binding sites mediating these interactions. We also show that the virus counters these interactions through its neuraminidase (NA) protein. These results emphasize the critical role played by NK cells in eliminating influenza, a significant cause of worldwide morbidity and mortality.
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Expansion of CD16 positive and negative human NK cells in response to tumor stimulation
Eur J Immunol.
NK cells are innate immune lymphocytes that express a vast repertoire of germ-line encoded receptors for target recognition. These receptors include inhibitory and activating proteins, among the latter of which is CD16, a low affinity binding Fc receptor. Here, we show that human NK cells expand in response to stimulation with various tumor cell lines. We further demonstrate that the tumor-derived expansion of NK cells is accompanied by rapid, cell-dependent, changes in CD16 expression levels…
NK cells are innate immune lymphocytes that express a vast repertoire of germ-line encoded receptors for target recognition. These receptors include inhibitory and activating proteins, among the latter of which is CD16, a low affinity binding Fc receptor. Here, we show that human NK cells expand in response to stimulation with various tumor cell lines. We further demonstrate that the tumor-derived expansion of NK cells is accompanied by rapid, cell-dependent, changes in CD16 expression levels. We show that in NK cells expanded in response to the EBV-transformed cell line 721.221, CD16 is shed and therefore approximately half of the expanded 721.221-derived NK-cell population does not express CD16. We also show, in contrast, that in response to 1106mel cells, CD16 expression is maintained on the cell surface of the expanded NK cells due to an antibody-dependent mechanism. Our results may provide a basis for the selective expansion of NK cells that may be used for tumor immunotherapy.
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The viral KSHV chemokine vMIP-II inhibits the migration of Naive and activated human NK cells by antagonizing two distinct chemokine receptors
Plos Pathog.
Natural killer (NK) cells are innate immune cells able to rapidly kill virus-infected and tumor cells. Two NK cell populations are found in the blood; the majority (90%) expresses the CD16 receptor and also express the CD56 protein in intermediate levels (CD56(Dim) CD16(Pos)) while the remaining 10% are CD16 negative and express CD56 in high levels (CD56(Bright) CD16(Neg)). NK cells also reside in some tissues and traffic to various infected organs through the usage of different chemokines and…
Natural killer (NK) cells are innate immune cells able to rapidly kill virus-infected and tumor cells. Two NK cell populations are found in the blood; the majority (90%) expresses the CD16 receptor and also express the CD56 protein in intermediate levels (CD56(Dim) CD16(Pos)) while the remaining 10% are CD16 negative and express CD56 in high levels (CD56(Bright) CD16(Neg)). NK cells also reside in some tissues and traffic to various infected organs through the usage of different chemokines and chemokine receptors. Kaposi's sarcoma-associated herpesvirus (KSHV) is a human virus that has developed numerous sophisticated and versatile strategies to escape the attack of immune cells such as NK cells. Here, we investigate whether the KSHV derived cytokine (vIL-6) and chemokines (vMIP-I, vMIP-II, vMIP-III) affect NK cell activity. Using transwell migration assays, KSHV infected cells, as well as fusion and recombinant proteins, we show that out of the four cytokine/chemokines encoded by KSHV, vMIP-II is the only one that binds to the majority of NK cells, affecting their migration. We demonstrate that vMIP-II binds to two different receptors, CX3CR1 and CCR5, expressed by naïve CD56(Dim) CD16(Pos) NK cells and activated NK cells, respectively. Furthermore, we show that the binding of vMIP-II to CX3CR1 and CCR5 blocks the binding of the natural ligands of these receptors, Fractalkine (Fck) and RANTES, respectively. Finally, we show that vMIP-II inhibits the migration of naïve and activated NK cells towards Fck and RANTES. Thus, we present here a novel mechanism in which KSHV uses a unique protein that antagonizes the activity of two distinct chemokine receptors to inhibit the migration of naïve and activated NK cells.
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Honors & Awards
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Faculty prize for best M.Sc thesis
The Hebrew University, Faculty of Medicine
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Rector Prize for first rate excellent students
The Hebrew University
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Award for outstanding students who did significant army service
Lenny Shapiro Foundation
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Dean's Scholarship
The Hebrew University
Languages
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Hebrew
Native or bilingual proficiency
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English
Professional working proficiency
Recommendations received
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מכירים את התחושה של פרפרים בבטן? איזו התרגשות…. חשבתי שלא ארגיש אותה לאחר שכול חיי עבדתי ברציפות ״בתפקיד חיי״, כך קראתי לעבודה שלי …. בתקופה…
מכירים את התחושה של פרפרים בבטן? איזו התרגשות…. חשבתי שלא ארגיש אותה לאחר שכול חיי עבדתי ברציפות ״בתפקיד חיי״, כך קראתי לעבודה שלי …. בתקופה…
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Looking forward to take part in this important meeting, and lead a round table discussion with my wonderful colleague Anat Boehm-Cagan (ענת…
Looking forward to take part in this important meeting, and lead a round table discussion with my wonderful colleague Anat Boehm-Cagan (ענת…
Liked by Yael Ophir
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Excited for the annual Drug Discovery Innovation Forum in Berlin! #DDISummit Come hear AION Labs board member and CTO of Merck Group Laura Matz and…
Excited for the annual Drug Discovery Innovation Forum in Berlin! #DDISummit Come hear AION Labs board member and CTO of Merck Group Laura Matz and…
Liked by Yael Ophir
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After nearly six incredible years at Startup Nation Central, the time has come for me to embark on a new journey. My experience here has been…
After nearly six incredible years at Startup Nation Central, the time has come for me to embark on a new journey. My experience here has been…
Liked by Yael Ophir
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We were honored to host the Techlinic delegation of healthcare leaders from east Jerusalem, participating in a healthcare innovation course by the…
We were honored to host the Techlinic delegation of healthcare leaders from east Jerusalem, participating in a healthcare innovation course by the…
Liked by Yael Ophir
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We are excited to announce that 40 talented professionals from Schneider Children's Medical Center of Israel, Dan-Petah Tikva, Sharon-Shomron, Carmel…
We are excited to announce that 40 talented professionals from Schneider Children's Medical Center of Israel, Dan-Petah Tikva, Sharon-Shomron, Carmel…
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#HealthAI #Ai is revolutionizing every aspect of our lives, including healthcare. But are we ready for this change? AI is transforming medical…
#HealthAI #Ai is revolutionizing every aspect of our lives, including healthcare. But are we ready for this change? AI is transforming medical…
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Back to work! Happy to be back at the office today after a great summer. Looking forward to a fall packed with great opportunities for Swedish Life…
Back to work! Happy to be back at the office today after a great summer. Looking forward to a fall packed with great opportunities for Swedish Life…
Liked by Yael Ophir
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I had the pleasure of hosting two senior participants from The Israeli National School for Leadership, Governance, and Management for a two-day…
I had the pleasure of hosting two senior participants from The Israeli National School for Leadership, Governance, and Management for a two-day…
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We are thrilled to announce that SHAARE ZEDEK MEDICAL CENTER JERUSALEM has reached a significant milestone of 4 MILLION medical images. Standing at…
We are thrilled to announce that SHAARE ZEDEK MEDICAL CENTER JERUSALEM has reached a significant milestone of 4 MILLION medical images. Standing at…
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