Prof. Eli Pikarsky
Phone: +972-2-6758202
Office:4315
Laboratory: 3303; Bldg. 3, Floor 3
Email: peli@hadassah.org.il
Research interests
Lab members
Research projects
Publications
major collaborations
Social activities
Research interests
Characterizing Inflammatory Links in Liver Cancer
The past few years yielded an explosion of exciting clinical trials showing the remarkable benefit of immune treatments in cancer patients. The link between inflammation and cancer is now established, yet the underlying molecular mechanisms are unresolved. As tumors progress, they modulate the inflammatory cells towards a protumorigenic immunosuppressive phenotype. We have shown that the inflammatory cells reciprocate by sculpting the parenchymal epithelial cells. We are studying these reciprocal interactions and hypothesize that they lie at the heart of the link between inflammation and cancer.
Liver cancer is the third most common cause of cancer-related death worldwide, and its dramatic three decades-long rise makes liver cancer the fastest-growing cause of deaths from cancer in the United States. Liver cancer is a prototype of inflammation induced cancer. We employ several strategies to analyze the changes that occur in inflammatory cells before and after liver tumor emergence, based on our preliminary findings showing that changes in inflammatory cells precede tumorigenesis. We are comprehensively mapping the changing inflammatory microenvironment in mouse models of inflammation induced Hepatocellular carcinoma (HCC) – the most common form of primary liver cancer. Using genetic manipulation strategies, coupled with cell isolation techniques we are delineating the molecular cues that mediate these changes and are analyzing the functional role of key mediators of these processes in the malignant process.
We have recently characterized a new form of inflammation which is characterized by the presence of focal collections of immune cells (also known as ectopic lymphoid like structures). Surprisingly, this form of inflammation promotes cancer growth by hijacking molecules which are secreted by lymphocytes, which are usually associated with anti-tumor responses. We are now testing how the new and exciting immune check point drugs interact with these foci. This could impact immunotherapy of cancer, wherein lymphocytes are usually considered positive mediators of anti-cancer responses.
Lab members
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Alumni
Dr. Udi Udi Gluschnaider, PhD
Dr. Shlomi Finkin, PhD
Dr. Simona Hefetz-Sela, PhD
Dr. David Knigin, MD-PhD
Dr. Ruth Peretz, MD-PhD
Dr. Rinnat Porat, PhD
Dr. Efi Weitman, DMD-PhD
Dr. Yoganathan Ramia Krishnamoorthy, PhD
Yousef Mansour, MSc
Funding
- Israel Science Foundation
- Israel Science Foundation – Israel Precision Medicine Partnership (IPMP) Program
- Adelson Medical Research Foundation (AMRF)
- German Cancer Research Center (DKFZ) – Israel Ministry of Science, Technology & Space (MOST) Program in Cancer Research
- Israel Ministry of Science, Technology & Space
Research projects
Immune-dependent liver micro niches foster tumor progenitors before they acquire self-sufficiency
Whereas the innate immune system often promotes carcinogenesis, adaptive immunity is known to have a tumor protective role. On the contrary, using a unique mouse model of HCC, we discovered a novel mechanism through which the adaptive immune system can critically support tumorigenesis. We generated genetically modified mice which express a constitutively active form of IKKβ, the upstream kinase of the NF-kB signaling pathway, specifically in hepatocytes (IKKβ(EE)Hep mice). The IKKβ(EE)Hep mouse model of HCC displays abundant hepatic ectopic lymphoid-like structures (ELSs) that are similar to their human equivalents in both cellular and cytokine composition. Inflammation usually entails a diffuse influx of immune cells, scattered throughout the inflamed tissue. However, infiltrating leukocytes often form ectopic lymphoid aggregates or even more complex structures that histologically resemble lymphoid organs. These structures direct various B and T cell responses and are referred to as ELSs. The mechanisms governing ELSs neogenesis, as their functional state in different pathologies, remain poorly defined. ELSs often develop at sites of chronic inflammation where they influence the course of many disease types, including distinct autoimmune, cardiovascular, metabolic and neurodegenerative diseases. Clinically, the presence of ELSs within inflamed tissues has been linked to both protective and deleterious outcomes in patients. In cancer the presence of tumor-associated ELSs usually correlates with a better prognosis and they are thought to coordinate endogenous antitumor immune responses (e.g. in melanoma, colorectal and breast cancer). Yet, in HCC we recently revealed a surprising protumorigenic role for ELSs, and found that they constitute immunopathological micro niches wherein progenitor malignant hepatocytes appear and thrive in a complex cellular and cytokine milieu until gaining to exert a cancer surveillance function, primarily acting to suppress tumorigenesis (For a brief animation please visit https://www.youtube.com/watch?v=gGCjekCl5O4). We are now testing whether these aberrant immune foci could serve as new targets for cancer therapy.
Epithelial p53 and the microenvironment – a continuous cross talk
p53 is a central hub in preventing cancer: it is regulated by multiple cellular signaling pathways and biochemical events and in turn regulates the expression of multiple target genes and can execute several cellular outcomes. However, as cancer develops in tissues it is only logical to assume that p53 could be regulated by, and in turn regulate, tissue level phenomena which transcend the cellular level. Indeed, we have recently noted that p53 regulates the crosstalk between gut epithelial cells and the underlying lamina propria, to preserve tissue boundaries. We will explore the hypothesis that inflammation, injury or repair change the amplitude or the spectrum of the p53 response in epithelial cells. We expect that tissue danger lowers the threshold for p53 activation and thus adds extra-protection. Furthermore, by modulating the nature of the p53 response, the tissue could adapt better to the changing environment. We will study the reciprocal hypothesis that p53 in epithelial cells modulates the state of the microenvironment in disease states. Thus, it is conceivable that genotoxic stress occurring in multiple epithelial cells (leading to p53 activation), should alter inflammatory processes, to modulate inflammation so that the latter will not increase cancer risk.
Metabolic control of sperm lineage transitions
We have recently established a novel method for isolating germ cells from mouse testis. Our method utilizes transgenic mice that express tomato fluorescent protein under germ cell specific promoter allowing us to perform sorting of cells by fluorescence activated cell sorting. We are able to isolate 7 distinct populations along the complex process of spermatogenesis: undifferentiated spermatogonia, differentiating spermatogonia, late spermatogonia, leptotene/zygotene (L/Z), pachytene, secondary spermatocytes and round spermatids.
This allowed us to characterize transcriptional and metabolic profiles of different stages, which suggest key involvement of metabolic pathways in controlling phenotypic transitions, tightly linked to the meiotic process, and likely affecting the balance between stemness and differentiation.
Our aim is to decipher the contribution of metabolic process that are uniquely active in specific stages of this intricate cell lineage to differentiation decisions. In addition to revealing the basic mechanisms of spermatogenesis we hope that our findings could open new ways for combatting infertility as well as germ cell tumors.
Publications
- Melamed, E., Martinovits, G., Pikarsky, E., Rosenthal, J. & Uzzan, A. Diphenylhydantoin and phenobarbital suppress the dopaminergic neurotoxicity of MPTP in mice. Eur J Pharmacol 128, 255-257 (1986).
- Melamed, E., Pikarsky, E., Goldberg, A., Rosenthal, J., Uzzan, A. & Conforti, N. Effect of serotonergic, corticostriatal and kainic acid lesions on the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) in mice. Brain Res 399, 178-180 (1986).
- Melamed, E., Soffer, D., Rosenthal, J., Pikarsky, E. & Reches, A. Effect of intrastriatal and intranigral administration of synthetic neuromelanin on the dopaminergic neurotoxicity of MPTP in rodents. Neurosci Lett 83, 41-46 (1987).
- Pikarsky, E., Melamed, E., Rosenthal, J., Uzzan, A. & Michowiz, S.D. The neurotoxin MPTP does not affect striatal superoxide dismutase activity in mice. Neurosci Lett 82, 327-331 (1987).
- Michowiz, S.D., Melamed, E., Pikarsky, E. & Rappaport, Z.H. Effect of ischemia induced by middle cerebral artery occlusion on superoxide dismutase activity in rat brain. Stroke 21, 1613-1617 (1990).
- Ben-Shushan, E., Pikarsky, E., Klar, A. & Bergman, Y. Extinction of Oct-3/4 gene expression in embryonal carcinoma x fibroblast somatic cell hybrids is accompanied by changes in the methylation status, chromatin structure, and transcriptional activity of the Oct-3/4 upstream region. Mol Cell Biol 13, 891-901 (1993).
- Pikarsky, E., Sharir, H., Ben-Shushan, E. & Bergman, Y. Retinoic acid represses Oct-3/4 gene expression through several retinoic acid-responsive elements located in the promoter-enhancer region. Mol Cell Biol 14, 1026-1038 (1994).
- Ben-Shushan, E., Sharir, H., Pikarsky, E. & Bergman, Y. A dynamic balance between ARP-1/COUP-TFII, EAR-3/COUP-TFI, and retinoic acid receptor:retinoid X receptor heterodimers regulates Oct-3/4 expression in embryonal carcinoma cells. Mol Cell Biol 15, 1034-1048 (1995).
- Nir-Paz, R., Ben-Chetrit, E., Pikarsky, E., Hassin, D., Hasin, Y. & Chajek-Shaul, T. Unusual presentation of familial Mediterranean fever: role of genetic diagnosis. Ann Rheum Dis 59, 836-838 (2000).
- Pikarsky, E. & Peretz, T. Bone marrow metastases in breast cancer. N Engl J Med 343, 577-578 (2000).
- Pikarsky, E., Maly, B. & Maly, A. Ceroid granuloma of the uterine cervix. Int J Gynecol Pathol 21, 191-193 (2002).
- Banin, E., Obolensky, A., Piontek, E., Falk, H., Pikarsky, E., Pe’er, J., Panet, A. & Chowers, I. Gene delivery by viral vectors in primary cultures of lacrimal gland tissue. Invest Ophthalmol Vis Sci 44, 1529-1533 (2003).
- Gidekel, S., Pizov, G., Bergman, Y. & Pikarsky, E. Oct-3/4 is a dose-dependent oncogenic fate determinant. Cancer Cell 4, 361-370 (2003).
- Hornstein, I., Pikarsky, E., Groysman, M., Amir, G., Peylan-Ramu, N. & Katzav, S. The haematopoietic specific signal transducer Vav1 is expressed in a subset of human neuroblastomas. J Pathol 199, 526-533 (2003).
- Lavon, I., Pikarsky, E., Gutkovich, E., Goldberg, I., Bar, J., Oren, M. & Ben-Neriah, Y. Nuclear factor-kappaB protects the liver against genotoxic stress and functions independently of p53. Cancer Res 63, 25-30 (2003).
- Darash-Yahana, M., Pikarsky, E., Abramovitch, R., Zeira, E., Pal, B., Karplus, R., Beider, K., Avniel, S., Kasem, S., Galun, E. & Peled, A. Role of high expression levels of CXCR4 in tumor growth, vascularization, and metastasis. FASEB J 18, 1240-1242 (2004).
- Goldenberg-Furmanov, M., Stein, I., Pikarsky, E., Rubin, H., Kasem, S., Wygoda, M., Weinstein, I., Reuveni, H. & Ben-Sasson, S.A. Lyn is a target gene for prostate cancer: sequence-based inhibition induces regression of human tumor xenografts. Cancer Res 64, 1058-1066 (2004).
- Pikarsky, E., Porat, R.M., Stein, I., Abramovitch, R., Amit, S., Kasem, S., Gutkovich-Pyest, E., Urieli-Shoval, S., Galun, E. & Ben-Neriah, Y. NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 431, 461-466 (2004).
- Pikarsky, E., Ronen, A., Abramowitz, J., Levavi-Sivan, B., Hutoran, M., Shapira, Y., Steinitz, M., Perelberg, A., Soffer, D. & Kotler, M. Pathogenesis of acute viral disease induced in fish by carp interstitial nephritis and gill necrosis virus. J Virol 78, 9544-9551 (2004).
- Kochupurakkal, B.S., Harari, D., Di-Segni, A., Maik-Rachline, G., Lyass, L., Gur, G., Kerber, G., Citri, A., Lavi, S., Eilam, R., Chalifa-Caspi, V., Eshhar, Z., Pikarsky, E., Pinkas-Kramarski, R., Bacus, S.S. & Yarden, Y. Epigen, the last ligand of ErbB receptors, reveals intricate relationships between affinity and mitogenicity. J Biol Chem 280, 8503-8512 (2005).
- Nickoloff, B.J., Ben-Neriah, Y. & Pikarsky, E. Inflammation and cancer: is the link as simple as we think? J Invest Dermatol 124, x-xiv (2005).
- Banin, E., Obolensky, A., Idelson, M., Hemo, I., Reinhardtz, E., Pikarsky, E., Ben-Hur, T. & Reubinoff, B. Retinal incorporation and differentiation of neural precursors derived from human embryonic stem cells. Stem Cells 24, 246-257 (2006).
- Daum, H., Sagi, M., Pikarsky, E., Pruss, D., Hamburger, T. & Peretz, T. [Prophylactic oophorectomy among carriers of BRCA1/2 mutations–demographic and pathologic data]. Harefuah 145, 13-17, 79-80 (2006).
- De Marzo, A.M., Platz, E.A., Epstein, J.I., Ali, T., Billis, A., Chan, T.Y., Cheng, L., Datta, M., Egevad, L., Ertoy-Baydar, D., Farre, X., Fine, S.W., Iczkowski, K.A., Ittmann, M., Knudsen, B.S., Loda, M., Lopez-Beltran, A., Magi-Galluzzi, C., Mikuz, G., Montironi, R., Pikarsky, E., Pizov, G., Rubin, M.A., Samaratunga, H., Sebo, T., Sesterhenn, I.A., Shah, R.B., Signoretti, S., Simko, J., Thomas, G., Troncoso, P., Tsuzuki, T.T., van Leenders, G.J., Yang, X.J., Zhou, M., Figg, W.D., Hoque, A. & Lucia, M.S. A working group classification of focal prostate atrophy lesions. Am J Surg Pathol 30, 1281-1291 (2006).
- Ezernitchi, A.V., Vaknin, I., Cohen-Daniel, L., Levy, O., Manaster, E., Halabi, A., Pikarsky, E., Shapira, L. & Baniyash, M. TCR zeta down-regulation under chronic inflammation is mediated by myeloid suppressor cells differentially distributed between various lymphatic organs. J Immunol 177, 4763-4772 (2006).
- Keshet, I., Schlesinger, Y., Farkash, S., Rand, E., Hecht, M., Segal, E., Pikarski, E., Young, R.A., Niveleau, A., Cedar, H. & Simon, I. Evidence for an instructive mechanism of de novo methylation in cancer cells. Nat Genet 38, 149-153 (2006).
- Klochendler-Yeivin, A., Picarsky, E. & Yaniv, M. Increased DNA damage sensitivity and apoptosis in cells lacking the Snf5/Ini1 subunit of the SWI/SNF chromatin remodeling complex. Mol Cell Biol 26, 2661-2674 (2006).
- Pikarsky, E. & Ben-Neriah, Y. NF-kappaB inhibition: a double-edged sword in cancer? Eur J Cancer 42, 779-784 (2006).
- Tshori, S., Gilon, D., Beeri, R., Nechushtan, H., Kaluzhny, D., Pikarsky, E. & Razin, E. Transcription factor MITF regulates cardiac growth and hypertrophy. J Clin Invest 116, 2673-2681 (2006).
- Bala, M., Lebenthal, A., Pikarsky, E., Faroja, M., Rivkind, A.I. & Mintz, Y. Intestinal stenosis causing small bowel obstruction after nonoperative management of blunt abdominal trauma. J Trauma 62, 1511-1513 (2007).
- Cohen, I., Maly, B., Simon, I., Meirovitz, A., Pikarsky, E., Zcharia, E., Peretz, T., Vlodavsky, I. & Elkin, M. Tamoxifen induces heparanase expression in estrogen receptor-positive breast cancer. Clin Cancer Res 13, 4069-4077 (2007).
- Kolodkin-Gal, D., Zamir, G., Pikarski, E., Pikarski, A., Shimony, N., Wu, H., Haviv, Y.S. & Panet, A. A novel system to study adenovirus tropism to normal and malignant colon tissues. Virology 357, 91-101 (2007).
- Natkunam, Y., Vainer, G., Chen, J., Zhao, S., Marinelli, R.J., Hammer, A.S., Hamilton-Dutoit, S., Pikarsky, E., Amir, G., Levy, R., Yisraeli, J.K. & Lossos, I.S. Expression of the RNA-binding protein VICKZ in normal hematopoietic tissues and neoplasms. Haematologica 92, 176-183 (2007).
- Yutkin, V., Pode, D., Pikarsky, E. & Mandelboim, O. The expression level of ligands for natural killer cell receptors predicts response to bacillus Calmette-Guerin therapy: a pilot study. J Urol 178, 2660-2664 (2007).
- Goldberg, Y., Porat, R.M., Kedar, I., Shochat, C., Sagi, M., Eilat, A., Mendelson, S., Hamburger, T., Nissan, A., Hubert, A., Kadouri, L., Pikarski, E., Lerer, I., Abeliovich, D., Bercovich, D. & Peretz, T. Mutation spectrum in HNPCC in the Israeli population. Fam Cancer 7, 309-317 (2008).
- Kolodkin-Gal, D., Zamir, G., Edden, Y., Pikarsky, E., Pikarsky, A., Haim, H., Haviv, Y.S. & Panet, A. Herpes simplex virus type 1 preferentially targets human colon carcinoma: role of extracellular matrix. J Virol 82, 999-1010 (2008).
- Lerner, I., Baraz, L., Pikarsky, E., Meirovitz, A., Edovitsky, E., Peretz, T., Vlodavsky, I. & Elkin, M. Function of heparanase in prostate tumorigenesis: potential for therapy. Clin Cancer Res 14, 668-676 (2008).
- Meyuhas, R., Pikarsky, E., Tavor, E., Klar, A., Abramovitch, R., Hochman, J., Lago, T.G. & Honigman, A. A Key role for cyclic AMP-responsive element binding protein in hypoxia-mediated activation of the angiogenesis factor CCN1 (CYR61) in Tumor cells. Mol Cancer Res 6, 1397-1409 (2008).
- Vainer, G., Vainer-Mosse, E., Pikarsky, A., Shenoy, S.M., Oberman, F., Yeffet, A., Singer, R.H., Pikarsky, E. & Yisraeli, J.K. A role for VICKZ proteins in the progression of colorectal carcinomas: regulating lamellipodia formation. J Pathol 215, 445-456 (2008).
- Vainer, G.W., Pikarsky, E. & Ben-Neriah, Y. Contradictory functions of NF-kappaB in liver physiology and cancer. Cancer Lett 267, 182-188 (2008).
- Vaknin, I., Blinder, L., Wang, L., Gazit, R., Shapira, E., Genina, O., Pines, M., Pikarsky, E. & Baniyash, M. A common pathway mediated through Toll-like receptors leads to T- and natural killer-cell immunosuppression. Blood 111, 1437-1447 (2008).
- Beider, K., Abraham, M., Begin, M., Wald, H., Weiss, I.D., Wald, O., Pikarsky, E., Abramovitch, R., Zeira, E., Galun, E., Nagler, A. & Peled, A. Interaction between CXCR4 and CCL20 pathways regulates tumor growth. PLoS One 4, e5125 (2009).
- Darash-Yahana, M., Gillespie, J.W., Hewitt, S.M., Chen, Y.Y., Maeda, S., Stein, I., Singh, S.P., Bedolla, R.B., Peled, A., Troyer, D.A., Pikarsky, E., Karin, M. & Farber, J.M. The chemokine CXCL16 and its receptor, CXCR6, as markers and promoters of inflammation-associated cancers. PLoS One 4, e6695 (2009).
- Kolodkin-Gal, D., Edden, Y., Hartshtark, Z., Ilan, L., Khalaileh, A., Pikarsky, A.J., Pikarsky, E., Rabkin, S.D., Panet, A. & Zamir, G. Herpes simplex virus delivery to orthotopic rectal carcinoma results in an efficient and selective antitumor effect. Gene Ther 16, 905-915 (2009).
- Lazer, G., Idelchuk, Y., Schapira, V., Pikarsky, E. & Katzav, S. The haematopoietic specific signal transducer Vav1 is aberrantly expressed in lung cancer and plays a role in tumourigenesis. J Pathol 219, 25-34 (2009).
- Nechushtan, H., Hamburger, T., Mendelson, S., Kadouri, L., Sharon, N., Pikarsky, E. & Peretz, T. Effects of the single nucleotide polymorphism at MDM2 309 on breast cancer patients with/without BRCA1/2 mutations. BMC Cancer 9, 60 (2009).
- Nemeth, J., Stein, I., Haag, D., Riehl, A., Longerich, T., Horwitz, E., Breuhahn, K., Gebhardt, C., Schirmacher, P., Hahn, M., Ben-Neriah, Y., Pikarsky, E., Angel, P. & Hess, J. S100A8 and S100A9 are novel nuclear factor kappa B target genes during malignant progression of murine and human liver carcinogenesis. Hepatology 50, 1251-1262 (2009).
- Toledano, H., Goldberg, Y., Kedar-Barnes, I., Baris, H., Porat, R.M., Shochat, C., Bercovich, D., Pikarsky, E., Lerer, I., Yaniv, I., Abeliovich, D. & Peretz, T. Homozygosity of MSH2 c.1906G–>C germline mutation is associated with childhood colon cancer, astrocytoma and signs of Neurofibromatosis type I. Fam Cancer 8, 187-194 (2009).
- Barash, H., E, R.G., Edrei, Y., Ella, E., Israel, A., Cohen, I., Corchia, N., Ben-Moshe, T., Pappo, O., Pikarsky, E., Goldenberg, D., Shiloh, Y., Galun, E. & Abramovitch, R. Accelerated carcinogenesis following liver regeneration is associated with chronic inflammation-induced double-strand DNA breaks. Proc Natl Acad Sci U S A 107, 2207-2212 (2010).
- Bitton-Worms, K., Pikarsky, E. & Aronheim, A. The AP-1 repressor protein, JDP2, potentiates hepatocellular carcinoma in mice. Mol Cancer 9, 54 (2010).
- Demaria, S., Pikarsky, E., Karin, M., Coussens, L.M., Chen, Y.C., El-Omar, E.M., Trinchieri, G., Dubinett, S.M., Mao, J.T., Szabo, E., Krieg, A., Weiner, G.J., Fox, B.A., Coukos, G., Wang, E., Abraham, R.T., Carbone, M. & Lotze, M.T. Cancer and inflammation: promise for biologic therapy. J Immunother 33, 335-351 (2010).
- Gielchinsky, Y., Laufer, N., Weitman, E., Abramovitch, R., Granot, Z., Bergman, Y. & Pikarsky, E. Pregnancy restores the regenerative capacity of the aged liver via activation of an mTORC1-controlled hyperplasia/hypertrophy switch. Genes Dev 24, 543-548 (2010).
- Gluschnaider, U., Hidas, G., Cojocaru, G., Yutkin, V., Ben-Neriah, Y. & Pikarsky, E. beta-TrCP inhibition reduces prostate cancer cell growth via upregulation of the aryl hydrocarbon receptor. PLoS One 5, e9060 (2010).
- Goldberg, Y., Porat, R.M., Kedar, I., Shochat, C., Galinsky, D., Hamburger, T., Hubert, A., Strul, H., Kariiv, R., Ben-Avi, L., Savion, M., Pikarsky, E., Abeliovich, D., Bercovich, D., Lerer, I. & Peretz, T. An Ashkenazi founder mutation in the MSH6 gene leading to HNPCC. Fam Cancer 9, 141-150 (2010).
- Kanarek, N., Horwitz, E., Mayan, I., Leshets, M., Cojocaru, G., Davis, M., Tsuberi, B.Z., Pikarsky, E., Pagano, M. & Ben-Neriah, Y. Spermatogenesis rescue in a mouse deficient for the ubiquitin ligase SCF{beta}-TrCP by single substrate depletion. Genes Dev 24, 470-477 (2010).
- Resnick, I., Stepensky, P., Elkin, G., Barkatz, C., Gurevich, O., Prigozhina, T., Pikarsky, E., Waldman, E., Amar, A., Samuel, S., Shapira, M., Weintraub, M. & Or, R. MSC for the improvement of hematopoietic engraftment. Bone Marrow Transplant 45, 605-606 (2010).
- Zaaroor-Regev, D., de Bie, P., Scheffner, M., Noy, T., Shemer, R., Heled, M., Stein, I., Pikarsky, E. & Ciechanover, A. Regulation of the polycomb protein Ring1B by self-ubiquitination or by E6-AP may have implications to the pathogenesis of Angelman syndrome. Proc Natl Acad Sci U S A 107, 6788-6793 (2010).
- Beider, K., Begin, M., Abraham, M., Wald, H., Weiss, I.D., Wald, O., Pikarsky, E., Zeira, E., Eizenberg, O., Galun, E., Hardan, I., Engelhard, D., Nagler, A. & Peled, A. CXCR4 antagonist 4F-benzoyl-TN14003 inhibits leukemia and multiple myeloma tumor growth. Exp Hematol 39, 282-292 (2011).
- Biton, M., Levin, A., Slyper, M., Alkalay, I., Horwitz, E., Mor, H., Kredo-Russo, S., Avnit-Sagi, T., Cojocaru, G., Zreik, F., Bentwich, Z., Poy, M.N., Artis, D., Walker, M.D., Hornstein, E., Pikarsky, E. & Ben-Neriah, Y. Epithelial microRNAs regulate gut mucosal immunity via epithelium-T cell crosstalk. Nat Immunol 12, 239-246 (2011).
- Elyada, E., Pribluda, A., Goldstein, R.E., Morgenstern, Y., Brachya, G., Cojocaru, G., Snir-Alkalay, I., Burstain, I., Haffner-Krausz, R., Jung, S., Wiener, Z., Alitalo, K., Oren, M., Pikarsky, E. & Ben-Neriah, Y. CKIalpha ablation highlights a critical role for p53 in invasiveness control. Nature 470, 409-413 (2011).
- Finkin, S. & Pikarsky, E. NF-kappaB in liver cancer: the plot thickens. Curr Top Microbiol Immunol 349, 185-196 (2011).
- Israeli, E., Yakunin, E., Zarbiv, Y., Hacohen-Solovich, A., Kisos, H., Loeb, V., Lichtenstein, M., Ben-Gedalya, T., Sabag, O., Pikarsky, E., Lorberboum-Galski, H. & Sharon, R. alpha-Synuclein expression selectively affects tumorigenesis in mice modeling Parkinson’s disease. PLoS One 6, e19622 (2011).
- Perets, R., Kaplan, T., Stein, I., Hidas, G., Tayeb, S., Avraham, E., Ben-Neriah, Y., Simon, I. & Pikarsky, E. Genome-wide analysis of androgen receptor targets reveals COUP-TF1 as a novel player in human prostate cancer. PLoS One 7, e46467 (2012).
- Barashi, N., Weiss, I.D., Wald, O., Wald, H., Beider, K., Abraham, M., Klein, S., Goldenberg, D., Axelrod, J., Pikarsky, E., Abramovitch, R., Zeira, E., Galun, E. & Peled, A. Inflammation-induced hepatocellular carcinoma is dependent on CCR5 in mice. Hepatology 58, 1021-1030 (2013).
- Cooks, T., Pateras, I.S., Tarcic, O., Solomon, H., Schetter, A.J., Wilder, S., Lozano, G., Pikarsky, E., Forshew, T., Rosenfeld, N., Harpaz, N., Itzkowitz, S., Harris, C.C., Rotter, V., Gorgoulis, V.G. & Oren, M. Mutant p53 prolongs NF-kappaB activation and promotes chronic inflammation and inflammation-associated colorectal cancer. Cancer Cell 23, 634-646 (2013).
- Pribluda, A., Elyada, E., Wiener, Z., Hamza, H., Goldstein, R.E., Biton, M., Burstain, I., Morgenstern, Y., Brachya, G., Billauer, H., Biton, S., Snir-Alkalay, I., Vucic, D., Schlereth, K., Mernberger, M., Stiewe, T., Oren, M., Alitalo, K., Pikarsky, E. & Ben-Neriah, Y. A senescence-inflammatory switch from cancer-inhibitory to cancer-promoting mechanism. Cancer Cell 24, 242-256 (2013).
- Pusterla, T., Nemeth, J., Stein, I., Wiechert, L., Knigin, D., Marhenke, S., Longerich, T., Kumar, V., Arnold, B., Vogel, A., Bierhaus, A., Pikarsky, E., Hess, J. & Angel, P. Receptor for advanced glycation endproducts (RAGE) is a key regulator of oval cell activation and inflammation-associated liver carcinogenesis in mice. Hepatology 58, 363-373 (2013).
- Sebban, S., Farago, M., Gashai, D., Ilan, L., Pikarsky, E., Ben-Porath, I. & Katzav, S. Vav1 fine tunes p53 control of apoptosis versus proliferation in breast cancer. PLoS One 8, e54321 (2013).
- Gluschnaider, U., Hertz, R., Ohayon, S., Smeir, E., Smets, M., Pikarsky, E. & Bar-Tana, J. Long-chain fatty acid analogues suppress breast tumorigenesis and progression. Cancer Res 74, 6991-7002 (2014).
- Hefetz-Sela, S., Stein, I., Klieger, Y., Porat, R., Sade-Feldman, M., Zreik, F., Nagler, A., Pappo, O., Quagliata, L., Dazert, E., Eferl, R., Terracciano, L., Wagner, E.F., Ben-Neriah, Y., Baniyash, M. & Pikarsky, E. Acquisition of an immunosuppressive protumorigenic macrophage phenotype depending on c-Jun phosphorylation. Proc Natl Acad Sci U S A 111, 17582-17587 (2014).
- Horwitz, E., Stein, I., Andreozzi, M., Nemeth, J., Shoham, A., Pappo, O., Schweitzer, N., Tornillo, L., Kanarek, N., Quagliata, L., Zreik, F., Porat, R.M., Finkelstein, R., Reuter, H., Koschny, R., Ganten, T., Mogler, C., Shibolet, O., Hess, J., Breuhahn, K., Grunewald, M., Schirmacher, P., Vogel, A., Terracciano, L., Angel, P., Ben-Neriah, Y. & Pikarsky, E. Human and mouse VEGFA-amplified hepatocellular carcinomas are highly sensitive to sorafenib treatment. Cancer Discov 4, 730-743 (2014).
- Kanarek, N., Grivennikov, S.I., Leshets, M., Lasry, A., Alkalay, I., Horwitz, E., Shaul, Y.D., Stachler, M., Voronov, E., Apte, R.N., Pagano, M., Pikarsky, E., Karin, M., Ghosh, S. & Ben-Neriah, Y. Critical role for IL-1beta in DNA damage-induced mucositis. Proc Natl Acad Sci U S A 111, E702-711 (2014).
- Sebban, S., Farago, M., Rabinovich, S., Lazer, G., Idelchuck, Y., Ilan, L., Pikarsky, E. & Katzav, S. Vav1 promotes lung cancer growth by instigating tumor-microenvironment cross-talk via growth factor secretion. Oncotarget 5, 9214-9226 (2014).
- Shilo, A., Ben Hur, V., Denichenko, P., Stein, I., Pikarsky, E., Rauch, J., Kolch, W., Zender, L. & Karni, R. Splicing factor hnRNP A2 activates the Ras-MAPK-ERK pathway by controlling A-Raf splicing in hepatocellular carcinoma development. RNA 20, 505-515 (2014).
- Yanger, K., Knigin, D., Zong, Y., Maggs, L., Gu, G., Akiyama, H., Pikarsky, E. & Stanger, B.Z. Adult hepatocytes are generated by self-duplication rather than stem cell differentiation. Cell Stem Cell 15, 340-349 (2014).
- Abu-Remaileh, M., Bender, S., Raddatz, G., Ansari, I., Cohen, D., Gutekunst, J., Musch, T., Linhart, H., Breiling, A., Pikarsky, E., Bergman, Y. & Lyko, F. Chronic inflammation induces a novel epigenetic program that is conserved in intestinal adenomas and in colorectal cancer. Cancer Res 75, 2120-2130 (2015).
- Falick Michaeli, T., Laufer, N., Sagiv, J.Y., Dreazen, A., Granot, Z., Pikarsky, E., Bergman, Y. & Gielchinsky, Y. The rejuvenating effect of pregnancy on muscle regeneration. Aging Cell 14, 698-700 (2015).
- Finkin, S., Yuan, D., Stein, I., Taniguchi, K., Weber, A., Unger, K., Browning, J.L., Goossens, N., Nakagawa, S., Gunasekaran, G., Schwartz, M.E., Kobayashi, M., Kumada, H., Berger, M., Pappo, O., Rajewsky, K., Hoshida, Y., Karin, M., Heikenwalder, M., Ben-Neriah, Y. & Pikarsky, E. Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma. Nat Immunol 16, 1235-1244 (2015).
- Gilad, R., Meir, K., Stein, I., German, L., Pikarsky, E. & Mabjeesh, N.J. High SEPT9_i1 protein expression is associated with high-grade prostate cancers. PLoS One 10, e0124251 (2015).
- Hefetz-Sela, S., Stein, I. & Pikarsky, E. Restoring inflammatory balance as a potential preventive strategy for inflammation induced cancer. Oncoimmunology 4, e1039764 (2015).
- Horwitz, E., Stein, I., Ben-Neriah, Y. & Pikarsky, E. Animal model studies indicate a candidate biomarker for sorafenib treatment of hepatocellular carcinoma. Mol Cell Oncol 2, e968028 (2015).
- Kravtsova-Ivantsiv, Y., Shomer, I., Cohen-Kaplan, V., Snijder, B., Superti-Furga, G., Gonen, H., Sommer, T., Ziv, T., Admon, A., Naroditsky, I., Jbara, M., Brik, A., Pikarsky, E., Kwon, Y.T., Doweck, I. & Ciechanover, A. KPC1-mediated ubiquitination and proteasomal processing of NF-kappaB1 p105 to p50 restricts tumor growth. Cell 161, 333-347 (2015).
- Lazar, C.H., Kimchi, A., Namburi, P., Mutsuddi, M., Zelinger, L., Beryozkin, A., Ben-Simhon, S., Obolensky, A., Ben-Neriah, Z., Argov, Z., Pikarsky, E., Fellig, Y., Marks-Ohana, D., Ratnapriya, R., Banin, E., Sharon, D. & Swaroop, A. Nonsyndromic Early-Onset Cone-Rod Dystrophy and Limb-Girdle Muscular Dystrophy in a Consanguineous Israeli Family are Caused by Two Independent yet Linked Mutations in ALMS1 and DYSF. Hum Mutat 36, 836-841 (2015).
- Abed, J., Emgard, J.E., Zamir, G., Faroja, M., Almogy, G., Grenov, A., Sol, A., Naor, R., Pikarsky, E., Atlan, K.A., Mellul, A., Chaushu, S., Manson, A.L., Earl, A.M., Ou, N., Brennan, C.A., Garrett, W.S. & Bachrach, G. Fap2 Mediates Fusobacterium nucleatum Colorectal Adenocarcinoma Enrichment by Binding to Tumor-Expressed Gal-GalNAc. Cell Host Microbe 20, 215-225 (2016).
- Aran, D., Lasry, A., Zinger, A., Biton, M., Pikarsky, E., Hellman, A., Butte, A.J. & Ben-Neriah, Y. Widespread parainflammation in human cancer. Genome Biol 17, 145 (2016).
- Darash-Yahana, M., Pozniak, Y., Lu, M., Sohn, Y.S., Karmi, O., Tamir, S., Bai, F., Song, L., Jennings, P.A., Pikarsky, E., Geiger, T., Onuchic, J.N., Mittler, R. & Nechushtai, R. Breast cancer tumorigenicity is dependent on high expression levels of NAF-1 and the lability of its Fe-S clusters. Proc Natl Acad Sci U S A 113, 10890-10895 (2016).
- Holt, S.H., Darash-Yahana, M., Sohn, Y.S., Song, L., Karmi, O., Tamir, S., Michaeli, D., Luo, Y., Paddock, M.L., Jennings, P.A., Onuchic, J.N., Azad, R.K., Pikarsky, E., Cabantchik, I.Z., Nechushtai, R. & Mittler, R. Activation of apoptosis in NAF-1-deficient human epithelial breast cancer cells. J Cell Sci 129, 155-165 (2016).
- Katlinskaya, Y.V., Katlinski, K.V., Lasri, A., Li, N., Beiting, D.P., Durham, A.C., Yang, T., Pikarsky, E., Lengner, C.J., Johnson, F.B., Ben-Neriah, Y. & Fuchs, S.Y. Type I Interferons Control Proliferation and Function of the Intestinal Epithelium. Mol Cell Biol 36, 1124-1135 (2016).
- Li, D., Fu, J., Du, M., Zhang, H., Li, L., Cen, J., Li, W., Chen, X., Lin, Y., Conway, E.M., Pikarsky, E., Wang, H., Pan, G., Ji, Y., Wang, H.Y. & Hui, L. Hepatocellular carcinoma repression by TNFalpha-mediated synergistic lethal effect of mitosis defect-induced senescence and cell death sensitization. Hepatology 64, 1105-1120 (2016).
- Llovet, J.M., Zucman-Rossi, J., Pikarsky, E., Sangro, B., Schwartz, M., Sherman, M. & Gores, G. Hepatocellular carcinoma. Nat Rev Dis Primers 2, 16018 (2016).
- Pikarsky, E. & Heikenwalder, M. Focal and Local: Ectopic Lymphoid Structures and Aggregates of Myeloid and Other Immune Cells in Liver. Gastroenterology 151, 780-783 (2016).
- Samarin, J., Laketa, V., Malz, M., Roessler, S., Stein, I., Horwitz, E., Singer, S., Dimou, E., Cigliano, A., Bissinger, M., Falk, C.S., Chen, X., Dooley, S., Pikarsky, E., Calvisi, D.F., Schultz, C., Schirmacher, P. & Breuhahn, K. PI3K/AKT/mTOR-dependent stabilization of oncogenic far-upstream element binding proteins in hepatocellular carcinoma cells. Hepatology 63, 813-826 (2016).
- Tarcic, O., Pateras, I.S., Cooks, T., Shema, E., Kanterman, J., Ashkenazi, H., Boocholez, H., Hubert, A., Rotkopf, R., Baniyash, M., Pikarsky, E., Gorgoulis, V.G. & Oren, M. RNF20 Links Histone H2B Ubiquitylation with Inflammation and Inflammation-Associated Cancer. Cell Rep 14, 1462-1476 (2016).
- Etzioni, A., Ciechanover, A. & Pikarsky, E. Immune defects caused by mutations in the ubiquitin system. J Allergy Clin Immunol 139, 743-753 (2017).
- Heikenwalder, M. & Pikarsky, E. Learning the Roles of the Hepatic Adaptive Immune System in Hepatocellular Carcinoma-Nature’s Guide for Successful Cancer Immunotherapy. Semin Liver Dis 37, 210-218 (2017).
- Malakar, P., Shilo, A., Mogilevsky, A., Stein, I., Pikarsky, E., Nevo, Y., Benyamini, H., Elgavish, S., Zong, X., Prasanth, K.V. & Karni, R. Long Noncoding RNA MALAT1 Promotes Hepatocellular Carcinoma Development by SRSF1 Upregulation and mTOR Activation. Cancer Res 77, 1155-1167 (2017).
- Roichman, A., Kanfi, Y., Glazz, R., Naiman, S., Amit, U., Landa, N., Tinman, S., Stein, I., Pikarsky, E., Leor, J. & Cohen, H.Y. SIRT6 Overexpression Improves Various Aspects of Mouse Healthspan. J Gerontol A Biol Sci Med Sci 72, 603-615 (2017).
- Tarcic, O., Granit, R.Z., Pateras, I.S., Masury, H., Maly, B., Zwang, Y., Yarden, Y., Gorgoulis, V.G., Pikarsky, E., Ben-Porath, I. & Oren, M. RNF20 and histone H2B ubiquitylation exert opposing effects in Basal-Like versus luminal breast cancer. Cell Death Differ 24, 694-704 (2017).
- Yuan, D., Huang, S., Berger, E., Liu, L., Gross, N., Heinzmann, F., Ringelhan, M., Connor, T.O., Stadler, M., Meister, M., Weber, J., Ollinger, R., Simonavicius, N., Reisinger, F., Hartmann, D., Meyer, R., Reich, M., Seehawer, M., Leone, V., Hochst, B., Wohlleber, D., Jors, S., Prinz, M., Spalding, D., Protzer, U., Luedde, T., Terracciano, L., Matter, M., Longerich, T., Knolle, P., Ried, T., Keitel, V., Geisler, F., Unger, K., Cinnamon, E., Pikarsky, E., Huser, N., Davis, R.J., Tschaharganeh, D.F., Rad, R., Weber, A., Zender, L., Haller, D. & Heikenwalder, M. Kupffer Cell-Derived Tnf Triggers Cholangiocellular Tumorigenesis through JNK due to Chronic Mitochondrial Dysfunction and ROS. Cancer Cell 31, 771-789 e776 (2017).
- Zick, A., Peretz, T., Lotem, M., Hubert, A., Katz, D., Temper, M., Rottenberg, Y., Uziely, B., Nechushtan, H., Meirovitz, A., Sonnenblick, A., Sapir, E., Edelman, D., Goldberg, Y., Lossos, A., Rosenberg, S., Fried, I., Finklstein, R., Pikarsky, E. & Goldshmidt, H. Treatment inferred from mutations identified using massive parallel sequencing leads to clinical benefit in some heavily pretreated cancer patients. Medicine (Baltimore) 96, e6931 (2017).
- Abu-Remaileh, M., Khalaileh, A., Pikarsky, E. & Aqeilan, R.I. WWOX controls hepatic HIF1alpha to suppress hepatocyte proliferation and neoplasia. Cell Death Dis 9, 511 (2018).
- Grinshpun, A., Gavert, N., Granit, R.Z., Masuri, H., Ben-Porath, I., Breuer, S., Zick, A., Rosenberg, S., Maoz, M., Granit, A., Pikarsky, E., Strausmman, R., Peretz, T. & Sonnenblick, A. Ev vivo organ culture as potential prioritization tool for breast cancer targeted therapy. Cancer Biol Ther 19, 645-648 (2018).
- Hanin, G., Yayon, N., Tzur, Y., Haviv, R., Bennett, E.R., Udi, S., Krishnamoorthy, Y.R., Kotsiliti, E., Zangen, R., Efron, B., Tam, J., Pappo, O., Shteyer, E., Pikarsky, E., Heikenwalder, M., Greenberg, D.S. & Soreq, H. miRNA-132 induces hepatic steatosis and hyperlipidaemia by synergistic multitarget suppression. Gut 67, 1124-1134 (2018).
- Minzel, W., Venkatachalam, A., Fink, A., Hung, E., Brachya, G., Burstain, I., Shaham, M., Rivlin, A., Omer, I., Zinger, A., Elias, S., Winter, E., Erdman, P.E., Sullivan, R.W., Fung, L., Mercurio, F., Li, D., Vacca, J., Kaushansky, N., Shlush, L., Oren, M., Levine, R., Pikarsky, E., Snir-Alkalay, I. & Ben-Neriah, Y. Small Molecules Co-targeting CKIalpha and the Transcriptional Kinases CDK7/9 Control AML in Preclinical Models. Cell 175, 171-185 e125 (2018).
- Pikarsky, E. Neighbourhood deaths cause a switch in cancer subtype. Nature 562, 45-46 (2018).
- Reizel, Y., Sabag, O., Skversky, Y., Spiro, A., Steinberg, B., Bernstein, D., Wang, A., Kieckhaefer, J., Li, C., Pikarsky, E., Levin-Klein, R., Goren, A., Rajewsky, K., Kaestner, K.H. & Cedar, H. Postnatal DNA demethylation and its role in tissue maturation. Nat Commun 9, 2040 (2018).
- Ringelhan, M., Pfister, D., O’Connor, T., Pikarsky, E. & Heikenwalder, M. The immunology of hepatocellular carcinoma. Nat Immunol 19, 222-232 (2018).
- Roth, L., Srivastava, S., Lindzen, M., Sas-Chen, A., Sheffer, M., Lauriola, M., Enuka, Y., Noronha, A., Mancini, M., Lavi, S., Tarcic, G., Pines, G., Nevo, N., Heyman, O., Ziv, T., Rueda, O.M., Gnocchi, D., Pikarsky, E., Admon, A., Caldas, C. & Yarden, Y. SILAC identifies LAD1 as a filamin-binding regulator of actin dynamics in response to EGF and a marker of aggressive breast tumors. Sci Signal 11 (2018).
- Roy, S., Hooiveld, G.J., Seehawer, M., Caruso, S., Heinzmann, F., Schneider, A.T., Frank, A.K., Cardenas, D.V., Sonntag, R., Luedde, M., Trautwein, C., Stein, I., Pikarsky, E., Loosen, S., Tacke, F., Ringelhan, M., Avsaroglu, S.K., Goga, A., Buendia, M.A., Vucur, M., Heikenwalder, M., Zucman-Rossi, J., Zender, L., Roderburg, C. & Luedde, T. microRNA 193a-5p Regulates Levels of Nucleolar- and Spindle-Associated Protein 1 to Suppress Hepatocarcinogenesis. Gastroenterology 155, 1951-1966 e1926 (2018).
- Shalom, B., Farago, M., Pikarsky, E. & Katzav, S. Vav1 mutations identified in human cancers give rise to different oncogenic phenotypes. Oncogenesis 7, 80 (2018).
- Izraely, S., Ben-Menachem, S., Sagi-Assif, O., Telerman, A., Zubrilov, I., Ashkenazi, O., Meshel, T., Maman, S., Orozco, J.I.J., Salomon, M.P., Marzese, D.M., Pasmanik-Chor, M., Pikarski, E., Ehrlich, M., Hoon, D.S.B. & Witz, I.P. The metastatic microenvironment: Melanoma-microglia cross-talk promotes the malignant phenotype of melanoma cells. Int J Cancer 144, 802-817 (2019).
- Malakar, P., Stein, I., Saragovi, A., Winkler, R., Stern-Ginossar, N., Berger, M., Pikarsky, E. & Karni, R. Long Noncoding RNA MALAT1 Regulates Cancer Glucose Metabolism by Enhancing mTOR-Mediated Translation of TCF7L2. Cancer Res 79, 2480-2493 (2019).
- Rosenfeld, Y.B., Krumbein, M., Yeffet, A., Schiffmann, N., Mishalian, I., Pikarsky, E., Oberman, F., Fridlender, Z. & Yisraeli, J.K. VICKZ1 enhances tumor progression and metastasis in lung adenocarcinomas in mice. Oncogene 38, 4169-4181 (2019).
- Wolf, Y., Bartok, O., Patkar, S., Eli, G.B., Cohen, S., Litchfield, K., Levy, R., Jimenez-Sanchez, A., Trabish, S., Lee, J.S., Karathia, H., Barnea, E., Day, C.P., Cinnamon, E., Stein, I., Solomon, A., Bitton, L., Perez-Guijarro, E., Dubovik, T., Shen-Orr, S.S., Miller, M.L., Merlino, G., Levin, Y., Pikarsky, E., Eisenbach, L., Admon, A., Swanton, C., Ruppin, E. & Samuels, Y. UVB-Induced Tumor Heterogeneity Diminishes Immune Response in Melanoma. Cell 179, 219-235 e221 (2019).
- Ansari, I., Raddatz, G., Gutekunst, J., Ridnik, M., Cohen, D., Abu-Remaileh, M., Tuganbaev, T., Shapiro, H., Pikarsky, E., Elinav, E., Lyko, F. & Bergman, Y. The microbiota programs DNA methylation to control intestinal homeostasis and inflammation. Nat Microbiol 5, 610-619 (2020).
- Azazmeh, N., Assouline, B., Winter, E., Ruppo, S., Nevo, Y., Maly, A., Meir, K., Witkiewicz, A.K., Cohen, J., Rizou, S.V., Pikarsky, E., Luxenburg, C., Gorgoulis, V.G. & Ben-Porath, I. Chronic expression of p16(INK4a) in the epidermis induces Wnt-mediated hyperplasia and promotes tumor initiation. Nat Commun 11, 2711 (2020).
- Ben-Hamo, R., Jacob Berger, A., Gavert, N., Miller, M., Pines, G., Oren, R., Pikarsky, E., Benes, C.H., Neuman, T., Zwang, Y., Efroni, S., Getz, G. & Straussman, R. Predicting and affecting response to cancer therapy based on pathway-level biomarkers. Nat Commun 11, 3296 (2020).
- Cinnamon, E. & Pikarsky, E. Are we ready for targeted therapy combinations in HCC? Gut 69, 613-614 (2020).
- Golubicki, M., Bonjoch, L., Acuna-Ochoa, J.G., Diaz-Gay, M., Munoz, J., Cuatrecasas, M., Ocana, T., Iseas, S., Mendez, G., Cisterna, D., Schubert, S.A., Nielsen, M., van Wezel, T., Goldberg, Y., Pikarsky, E., Robbio, J., Roca, E., Castells, A., Balaguer, F., Antelo, M. & Castellvi-Bel, S. Germline biallelic Mcm8 variants are associated with early-onset Lynch-like syndrome. JCI Insight 5 (2020).
- Kadosh, E., Snir-Alkalay, I., Venkatachalam, A., May, S., Lasry, A., Elyada, E., Zinger, A., Shaham, M., Vaalani, G., Mernberger, M., Stiewe, T., Pikarsky, E., Oren, M. & Ben-Neriah, Y. The gut microbiome switches mutant p53 from tumour-suppressive to oncogenic. Nature 586, 133-138 (2020).
- Kravtsova-Ivantsiv, Y., Goldhirsh, G., Ivantsiv, A., Ben Itzhak, O., Kwon, Y.T., Pikarsky, E. & Ciechanover, A. Excess of the NF-kB p50 subunit generated by the ubiquitin ligase KPC1 suppresses tumors via PD-L1- and chemokines-mediated mechanisms. Proc Natl Acad Sci U S A 117, 29823-29831 (2020).
- Landolina, N., Zaffran, I., Smiljkovic, D., Serrano-Candelas, E., Schmiedel, D., Friedman, S., Arock, M., Hartmann, K., Pikarsky, E., Mandelboim, O., Martin, M., Valent, P. & Levi-Schaffer, F. Activation of Siglec-7 results in inhibition of in vitro and in vivo growth of human mast cell leukemia cells. Pharmacol Res 158, 104682 (2020).
- Massalha, H., Bahar Halpern, K., Abu-Gazala, S., Jana, T., Massasa, E.E., Moor, A.E., Buchauer, L., Rozenberg, M., Pikarsky, E., Amit, I., Zamir, G. & Itzkovitz, S. A single cell atlas of the human liver tumor microenvironment. Mol Syst Biol 16, e9682 (2020).
- Romaniello, D., Marrocco, I., Belugali Nataraj, N., Ferrer, I., Drago-Garcia, D., Vaknin, I., Oren, R., Lindzen, M., Ghosh, S., Kreitman, M., Kittel, J.C., Gaborit, N., Bergado Baez, G., Sanchez, B., Eilam, R., Pikarsky, E., Paz-Ares, L. & Yarden, Y. Targeting HER3, a Catalytically Defective Receptor Tyrosine Kinase, Prevents Resistance of Lung Cancer to a Third-Generation EGFR Kinase Inhibitor. Cancers (Basel) 12 (2020).
- Salaymeh, Y., Farago, M., Sebban, S., Shalom, B., Pikarsky, E. & Katzav, S. Vav1 and mutant K-Ras synergize in the early development of pancreatic ductal adenocarcinoma in mice. Life Sci Alliance 3 (2020).
- Alfi, O., Yakirevitch, A., Wald, O., Wandel, O., Izhar, U., Oiknine-Djian, E., Nevo, Y., Elgavish, S., Dagan, E., Madgar, O., Feinmesser, G., Pikarsky, E., Bronstein, M., Vorontsov, O., Jonas, W., Ives, J., Walter, J., Zakay-Rones, Z., Oberbaum, M., Panet, A. & Wolf, D.G. Human Nasal and Lung Tissues Infected Ex Vivo with SARS-CoV-2 Provide Insights into Differential Tissue-Specific and Virus-Specific Innate Immune Responses in the Upper and Lower Respiratory Tract. J Virol 95, e0013021 (2021).
- Llovet, J.M., Kelley, R.K., Villanueva, A., Singal, A.G., Pikarsky, E., Roayaie, S., Lencioni, R., Koike, K., Zucman-Rossi, J. & Finn, R.S. Hepatocellular carcinoma. Nat Rev Dis Primers 7, 6 (2021).
- Zhang, P., Fischer, A., Ouyang, Y., Wang, J., Sohn, Y.S., Nechushtai, R., Pikarsky, E., Fan, C. & Willner, I. Aptamer-modified DNA tetrahedra-gated metal-organic framework nanoparticle carriers for enhanced chemotherapy or photodynamic therapy. Chem Sci 12, 14473-14483 (2021).
- Zhang, P., Ouyang, Y., Sohn, Y.S., Nechushtai, R., Pikarsky, E., Fan, C. & Willner, I. pH- and miRNA-Responsive DNA-Tetrahedra/Metal-Organic Framework Conjugates: Functional Sense-and-Treat Carriers. ACS Nano 15, 6645-6657 (2021).
- Britan-Rosich, Y., Ma, J., Kotler, E., Hassan, F., Botvinnik, A., Smith, Y., Moshel, O., Nasereddin, A., Sharma, G., Pikarsky, E., Ross, S. & Kotler, M. APOBEC3G protects the genome of human cultured cells and mice from radiation-induced damage. FEBS J (2022).
- Chen, X., Wang, Y., Dai, X., Ding, L., Chen, J., Yao, G., Liu, X., Luo, S., Shi, J., Wang, L., Nechushtai, R., Pikarsky, E., Willner, I., Fan, C. & Li, J. Single-Stranded DNA-Encoded Gold Nanoparticle Clusters as Programmable Enzyme Equivalents. J Am Chem Soc 144, 6311-6320 (2022).
- Cinnamon, E. & Pikarsky, E. Combining immune checkpoint inhibitors with immunomodulators: Lessons from different metastatic sites. Hepatology 76, 561-563 (2022).
- Fischer, A., Zhang, P., Ouyang, Y., Sohn, Y.S., Karmi, O., Nechushtai, R., Pikarsky, E. & Willner, I. DNA-Tetrahedra Corona-Modified Hydrogel Microcapsules: “Smart” ATP- or microRNA-Responsive Drug Carriers. Small, e2204108 (2022).
- Kolodkin-Gal, D., Roitman, L., Ovadya, Y., Azazmeh, N., Assouline, B., Schlesinger, Y., Kalifa, R., Horwitz, S., Khalatnik, Y., Hochner-Ger, A., Imam, A., Demma, J.A., Winter, E., Benyamini, H., Elgavish, S., Khatib, A.A., Meir, K., Atlan, K., Pikarsky, E., Parnas, O., Dor, Y., Zamir, G., Ben-Porath, I. & Krizhanovsky, V. Senolytic elimination of Cox2-expressing senescent cells inhibits the growth of premalignant pancreatic lesions. Gut 71, 345-355 (2022).
- Llovet, J.M., Castet, F., Heikenwalder, M., Maini, M.K., Mazzaferro, V., Pinato, D.J., Pikarsky, E., Zhu, A.X. & Finn, R.S. Immunotherapies for hepatocellular carcinoma. Nat Rev Clin Oncol 19, 151-172 (2022).
- Ouyang, Y., Fadeev, M., Zhang, P., Carmieli, R., Li, J., Sohn, Y.S., Karmi, O., Nechushtai, R., Pikarsky, E., Fan, C. & Willner, I. Aptamer-Modified Au Nanoparticles: Functional Nanozyme Bioreactors for Cascaded Catalysis and Catalysts for Chemodynamic Treatment of Cancer Cells. ACS Nano (2022).
- Shalom, B., Farago, M., Salaymeh, Y., Sebban, S., Pikarsky, E. & Katzav, S. Vav1 Promotes B-Cell Lymphoma Development. Cells 11 (2022).
- Shalom, B., Farago, M., Salaymeh, Y., Sebban, S., Risling, M., Pikarsky, E. & Katzav, S. Vav1 accelerates Ras-driven lung cancer and modulates its tumor microenvironment. Cell Signal 97, 110395 (2022).
- Venkatachalam, A., Pikarsky, E. & Ben-Neriah, Y. Putative homeostatic role of cancer driver mutations. Trends Cell Biol 32, 8-17 (2022).
- Zhang, P., Ouyang, Y., Sohn, Y.S., Fadeev, M., Karmi, O., Nechushtai, R., Stein, I., Pikarsky, E. & Willner, I. miRNA-Guided Imaging and Photodynamic Therapy Treatment of Cancer Cells Using Zn(II)-Protoporphyrin IX-Loaded Metal-Organic Framework Nanoparticles. ACS Nano 16, 1791-1801 (2022).
- Mayorek, N., Schlossberg, M., Mansour, Y., Pillar, N., Stein, I., Mushasha, F., Baziza, G., Medvedev, E., Manevitch, Z., Menzel, J., Aizenshtein, E., Sarvin, B., Sarvin, N., Shlomi, T., Klutstein, M., & Pikarsky, E. 2-hydroxyglutarate controls centromere and heterochromatin conformation and function in the male germline. bioRxiv 2022.05.29.493890; doi: https://doi.org/10.1101/2022.05.29.493890.
- Cinnamon, E., Stein, I., Zino, E., Rabinovich, S., Shovman, Y., Schlesinger, Y., Salame, T-M., Reich-Zeliger, S., Lotem, M., Ben-Neriah, Y., Parnas, O. & Pikarsky, E. RORc expressing immune cells support pro-tumorigenic functions of tertiary lymphoid structures. bioRxiv 2022.07.02.498540; doi: https://doi.org/10.1101/2022.07.02.498540.
major collaborations
- Yinon Ben-Neriah, Hebrew University, Jerusalem, Israel
- Yehudit Bergman, Hebrew University, Jerusalem, Israel
- Aaron Ciechanover, Rappaport Faculty of Medicine and Research Institute, Haifa, Israel
- Mathias Heikenwalder, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Shulamit Katzav, Hebrew University, Jerusalem, Israel
- Ana Martin-Villalba, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Moshe Oren, Weizmann Institute of Science, Rehovot, Israel
- Oren Parnas, Hebrew University, Jerusalem, Israel
- Itamar Willner, Hebrew University, Jerusalem, Israel
- Rachel Nechushtai, Hebrew University, Jerusalem, Israel
- Nir Yosef, Weizmann Institute of Science, Rehovot, Israel
Social activities