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Researchers
  • Prof.  Rotem Karni
 
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Research Interests
Prof. Karni's lab is interested in how the process of alternative RNA splicing (a fundamental step of gene expression) is de-regulated in cancer and other diseases, and how the proteins that control this process (called splicing factors) contribute to cancer development, tumor progression and the metastatic process. Another effort in the lab is to identify the genes which are regulated by each splicing factor. The Karni lab uses different in vitro and in vivo cellular and animal systems as well as new technologies such as RNA-seq to identify the role of splicing factors in cancer and their target genes. There are many important application to the studies in the lab, among them discovery of early diagnostic markers for tumor development and patient prognosis as well as new targets for the development of new anti-cancer therapies. Some of these applications are commercialized by the technology transfer company of the Hebrew University, Yissum. Prof. Karni's research is being supported by grants from the Israel Science Foundation (ISF), US-Israel Binational Foundation (BSF), Minerva foundation ARCHES award (Germany), Marie Curie (EU FP7), Israel Cancer Research Foundation (ICRF), American Cancer Society, Israel Cancer Association, Voices Against Brain Cancer, Fritz Thyssen Foundation and others.
 
mknk2.jpg
Splicing factor oncoprotein SRSF1 is a transcriptional target of the c-myc proto-oncogene, and can be phosphorylated by SRPK or CLK downstream to Akt. SRSF1 alters the splicing of BIM, BIN1, S6K1 and Mnk2 regulating the mTOR and MAPK pathways, increasing translation and inhibiting apoptosis.

 
 
Current Projects
To study the mechanisms of SRSF1 oncogenic activity in cancer. 
To characterize the oncogenic and biochemical properties of S6K1 splicing isoforms and their role in cancer and signaling. 
To characterize the oncogenic and biochemical properties of MNK2 splicing isoforms and their role in cancer and signal transduction..
 To study the role of hnRNP A2/B1 in brain cancer (glioblastoma), Hepatocellular carcinoma and metastatic breast cancer.
 To identify the splicing changes that occur in ovarian tumor metastasis and their contribution to the metastatic process.
 To study the role of Insulin receptor alternative splicing and other splicing changes in beta cell survival and diabetes.
 
 
Laboratory Members
Prof. Rotem Karni,Ph.D.
Principal Investigator
rotemka@ekmd.huji.ac.il
Dr. Zahava Kluger
Lab Manager
Dr. Regina Golan-Gerstl
Postdoctoral Fellow
regina.golan-gerstl@mail.huji.ac.il
Dr. Pushkar Malakar
Postdoctoral Fellow
pushkarm@ekmd.huji.ac.il
Asaf Shilo
Ph.D. Student
asaf.shilo@mail.huji.ac.il
Polina Denichenko
Ph.D. Student
Vered Ben-Hur
Ph.D. Student
yosefzon.vered@mail.huji.ac.il  
Maxim Mogilevsky
Ph.D. Student
maxim.mogilevsky@mail.huji.ac.il
 
 
Adi Rosenberg
M.Sc. Student
Liat Hay
M.Sc. Student
 
 
Adi Amar
Undergrad Student
Alona Peretz
Undergrad student
alona.peretz@mail.huji.ac.il
 
 
 
Former lab members
Michal Cohen-Eliev (M. Sc). Now at Shaare Zedec Medical Center
Lital Chartarifsky (M. Sc). Now a Ph.D. sudent, Watson School, CSHL, NY.
Ariel Sebag-Shimoni (Ph.D.) 
Avi Maimon (Ph.D.). Now a postdoc in the faculty of Dental Medicine.
Ilana Loinger-Lebenthal (Postdoc)
 
 
Curriculum Vitae
Education 
 
Institution and Location Degree Years Field of Study
The Hebrew University of Jerusalem
The Hebrew University of Jerusalem
Cold Spring Harbor Laboratory, NY 
B.Sc.
Ph.D.
Postdoc 
1994-1996
1998-2002
2002-2007
Biology
Biological Chemistry
Biochem./Mol. Biology 
Positions and Honors.
1997-2002
 
Teaching Assistant in various biochemistry courses at undergraduate and post-graduate levels at The University of Jerusalem
1998-2002
 
Ph.D. student in the Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem (Advisor: Alex Levitzki)
2002-2007 Postdoctoral Fellow, Cold Spring Harbor Laboratory (Mentor: Adrian R. Krainer)
2008-2009 Lecturer, The Hebrew University of Jerusalem, Hadassah Medical School.
2009-2001 Senior Lecturer, The Hebrew University of Jerusalem, Hadassah Medical School.
2014 Associate Professor, The Hebrew University of Jerusalem, Hadassah Medical School.
 
Awards
1998
 
The Polack Prize for excellence in studies and research from The Institute of Life Sciences, The Hebrew University of Jerusalem
1999 ASBMB/PABMB Graduate/Postdoctoral Travel Award (San Francisco) - poster and lecture
2000 EMBL/SALK/EMBO Conference on "Oncogenes and Growth Control", Heidelberg, Germany - lecture
2001
Noah Lichtenstein Prize, The Department of Biological Chemistry, The Hebrew University of Jerusalem
2001-2002 Yitzhak and Salve Hazelkorn Scholarship for excellence in PhD studies.
2009
 
 
Award for Research Cooperation and High Excellence in Science (ARCHES) from the Minerva stiftung foundation and the German ministry of education and research (BMBF). Presented by the German federal minister of education and research Prof. Annette Schavan.
2010 Award from the Israel Cancer Association
2012
Faculty of Medicine Prize for excellent research work by young investigator 
2013
Teva founders prize for excellent young researchers
2014 Matzner prize for excellant young investigator, Faculty of Medicine.
 
Invited/selected lectures
2005
 
RNA society meeting, Banf, Canada, selected lecture.
Eukaryotic mRNA processing meeting, CSH, NY, selected lecture.
2006 Mechanisms and models of cancer meeting, CSH, NY, selected lecture
2007
 
Eukaryotic mRNA processing Meeting, CSH, NY, selected lecture.
The “young seminar”, Hebrew university of Jerusalem Faculty of Medicine, Invited Lecture
2008
 
 
Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Invited Lecture;
RNA society meeting, Berlin, Germany, selected lecture;
Department of Biological Regulation, Weizmann Institute of Science, Invited lecture.
2009
 
 
Department of cell biology, Tel Aviv University; Department of Biology, Bar Ilan University; Department of Biology, Technion, EURAS net international meeting on Alternative splicing in neurodegeneration diseases and cancer, Tel Aviv, Invited Lectures.
2010
  
Department of Biological Chemistry, HUJI, Department of Developmental Biology and Cancer Research, HUJI, Israeli Association of Cancer Research second meeting, Weizmann Institute of Science, Invited lectures.
2011
 
 
 
6th FISEB/ILANIT conference, Eilat, Israel; BIT's 2nd World DNA and Genome Day, Dailan, China;‏ Department of Biological Chemistry, Weizmann Institute, Invited lectures.
Israel Cancer Association meeting; Protein Kinases Regulating Alternative splicing meeting,   
Roscoff, France, Invited lectures.
2012
 
 
Israel Society for Cancer Research (ISCR) annual meeting, Bar Ilan Univ; 17th World Congress on Advances in Oncology and 15th International Symposium on Molecular Medicine, Greece; Institute for Drug Research, HUJI; Post-EURASNET meeting, Trieste, Italy, ISOBM 2012 Congress, Jerusalem, Invited lectures. 
2013
 
Israeli Society of Physiology and Pharmacology (ISPP), Invited lecture. RNA society meeting, Davos, Switzerland, Selected lecture; IATI-Biomed 2013 Conference, Invited lecture.  
2014 RNA society meeting, Quebec city, Canada, selected lecture.  
 
Memberships/Editorial and Advisory boards
 -Israel Association for Cancer Research
 -European Association for Cancer Research
 -European Association for the Study of Diabetes (EASD)
 -Editorial Board member: American Journal of Cancer Research
 -Medical Advisory board of Voices Against Brain Cancer, NY.
 
Selected peer-reviewed publications (in chronological order)
Rotem Karni, Richard Jove and Alexander Levitzki. (1999). Inhibition of pp60c-Src reduces Bcl-XL levels and reverses the transformed phenotype of cells overexpressing EGF and HER-2 receptors. Oncogene 18:4654-4662 (127 citations*)
 
Rotem Karni, Richard Jove and Alexander Levitzki. (1999). Inhibition of pp60c-Src reduces Bcl-XL levels and reverses the transformed phenotype of cells overexpressing EGF and HER-2 receptors. Oncogene 18:4654-4662 (127 citations*)
 
Rotem Karni and Alexander Levitzki. (2000). c-Src is a caspase-3 substrate and is essential for the transformed phenotype of A431 cells. Mol. Cell. Biol. Res. Com. 3, 98-104. (25 citations)
 
Rotem Karni, Yuval Dor, Oded Meyuhas, Eli Keshet and Alexander Levitzki. (2002) Activated pp60c-Src Leads to Elevated HIF-1 expression Under Normoxia. J. Biol. Chem. 277(45):42919-42925. (72 citations*)
 
Rotem Karni, Sarit Mizrachi Aviv Gazit, Ella Reiss-Sklan, Oded Livnah and Alexander Levitzki. (2003) The pp60c-Src inhibitor PP1 is non-competitive against ATP. FEBS Lett. 537(1-3):47-52. (54 citations*)
 
Rotem Karni, Yael Gus, Yuval Dor, Oded Meyuhas and Alexander Levitzki. (2005) Active Src Elevates The Expression of ß-catenin by Enhancement of Cap-dependent Translation. Mol. Cell Biol. 12:5031-9 (25 citations*)
 
Rotem Karni, Elisa de-Stanchina, David Mu, Scott Lowe, Rahul Sinha and Adrian Krainer. (2007) The gene coding for the splicing factor SF2/ASF is a proto-oncogene Nat Struct Mol Biol. 14(3):185-93. (231 citations*)
 b. highlighted in Nature Reviews Cancer
 
Yael Gus, Rotem Karni and Alexander Levitzki. (2007) Subunit S5a of the 26S proteasome is regulated by antiapoptotic signals. FEBS J. 274:2815-31. (3 citations*)
 
Rotem Karni, Yoshitaka hippo, Scott Lowe and Adrian Krainer. (2008) The splicing factor oncoprotein SF2/ASF activates mTORC1. Proc. Natl. Acad. Sci. USA, 105:15323-7. (37 citations*)
 
Shuying Sun, Zuo Zhang, Rahul Sinha, Rotem Karni and Adrian R. Krainer (2010) SF2/ASF Autoregulation Involves Multiple Mechanisms. Nat Struct Mol Biol. 17: 306-12 (35 citations*)
 
Rahul Sinha, Eric Allemand, Zuo Zhang, Rotem Karni, Michael P. Myers and Adrian Krainer (2010). Arginine Methylation Controls the Subcellular Localization and Functions of the Oncoprotein Splicing Factor SF2/ASF. Mol Cell Biol. 30: 2762-74. (16 citations*)
 
Kasper Thorsen, Francisco Mansilla, Troels Schepeler, Bodil Øster, Mads H. Rasmussen, Lars Dyrskjøt, Rotem Karni, Martin Akerman, Adrian R. Krainer, Søren Laurberg, Claus L. Andersen and Torben F. Ørntoft (2011). Alternative splicing of SLC39A14 in colorectal cancer is regulated by the Wnt pathway. Mol Cell Proteomics. 10(1):M110.002998. (2 citations*)
 
Shay Porat, Noa Weinberg-Corem, Sharona Tornovsky-Babaey, Rachel Schyr-Ben-Haroush, Ayat Hija, Miri Stolovich-Rain, Daniela Dadon, Zvi Granot, Vered Ben-Hur, Peter White, Christophe A. Girard, Rotem Karni, Klaus H. Kaestner, Frances M . Ashcroft, Mark A. Magnuson, Ann Saada, Joseph Grimsby, Benjamin Glaser and Yuval Dor (2011). Control of Pancreatic β Cell Regeneration by Glucose Metabolism. Cell Metab. 13: 440-9. (43 citations*)
 
Regina Golan-Gerstl, Michal Cohen, Asaf Shilo, Sung Suk Suh, Arianna Bakacs, Luigi Coppola, and Rotem Karni (2011). Splicing factor hnRNP A2/B1 regulates tumor suppressor gene splicing and is an oncogenic driver in glioblastoma. Cancer Res. 71, 4464-72. (10 citations*) *Highlighted in Nature Reviews Cancer
 
Anczuków, O., Rosenberg, A.Z., Akerman, M., Das, S., Zhan, L., Karni, R., Muthuswamy, S.K. and Krainer, A.R. (2012). The splicing factor SRSF1 regulates apoptosis and proliferation to promote mammary epithelial cell transformation. Nat Struct Mol Biol. 19: 220-8. (16 citations*)
 
Sebban, S., Golan-Gerstl, R., Karni, R., Vaksman, O., Davidson, B. and Reich, R. (2013). Alternatively spliced lysyl oxidase-like 4 isoforms have a pro-metastatic role in cancer. Clin Exp Metastasis. 30: 103-17. (2 citations*)
 
Eshar, S., Allemand, E., Sebag, A., Glaser, F., Muchardt, C., Mandel-Gutfreund, Y., Karni, R. and Dzikowski R. (2012). A novel Plasmodium falciparum SR protein is an alternative splicing factor required for the parasites' proliferation in human erythrocytes. Nucleic Acids Res. 40: 9903-16. (1 citation*)
 
Li, D., Yang, H., Nan, H., Liu, P., Pang, S., Zhao, Q., Karni, R., Kamps, M.P., Xu, Y., Zhou, J., Wiedmer, T., Sims, P.J. and Wang, F. (2012). Identification of key regulatory pathways of myeloid differentiation using an mESC-based karyotypically normal cell model. Blood. 120: 4712-9. (1 citation*)
 
Michal Cohen-Aliev, Regina Golan-Gerstl, Zahava Siegfried, Claus L. Andersen, Kasper Thorsen, Torben F. Ørntoft, David Mu and Rotem Karni (2013). The splicing factor SRSF6 is amplified and is an oncoprotein in lung and colon cancers. J Pathol. 229: 630-9. (1 citations*)
 
Ben Hur, V., Denichenco, P., Maimon, A., Krainer, A., Davidson, B. and Karni, R. (2013). S6K1 alternative splicing modulates its oncogenic activity and regulates mTORC1 Cell Reports, 3: 103–115.
 
Hochberg, M., Gilead, L., Safran, M., Markel, G., Nemlich, Y., Enk, D., Denichenko, P., Karni, R. and Ingber, A. (2013). Insulin-like Growth Factor Binding Protein-7 (IGFBP7) transcript: A-to-I editing events in normal and cancerous human keratinocytes. Arch Dermatol Res. in press
 
Shimoni-Sebag, A., Lebenthal-Loinger, I., Zender, L. and Karni, R. (2013). RRM1 domain of the splicing oncoprotein SRSF1 is required for MEK1-MAPK-ERK activation and cellular transformation. Carcinogenesis. 34: 2498-504.
 
Siegfried, Z., Bonomi, S., Ghigna, C. and Karni, R. (2013). Regulation of the Ras-MAPK and PI3K-mTOR signalling pathways by alternative splicing in cancer. Int J Cell Biol. (Review). 2013: ID 568931.
 
Maimon, A., Mogilevsky, M., Shilo, A., Golan-Gerstl, R., Obiedat, A., Ben-Hur, V., Lebenthal-Loinger, I., Stein, I., Reich, R., Beenstock, J., Zehorai, E., Andersen, C.L., Thorsen, K., Orntoft, T.F., Davis, R.J., Davidson, B., Mu, D. and Karni, R. (2014). Mnk2 alternative splicing inactivates its tumor suppressor activity which is    a modulator of the p38-MAPK stress pathway. Cell Rep. 7: 501-13.
 
Shilo, A., Ben Hur, V., Denichenko, P., Stein, I., Pikarsky, E., Rauch, J., Kolch, W., Zender, L. and Karni, R. (2013) Splicing Factor hnRNP A2/B1 activates the Ras-MAPK-ERK pathway controlling A-Raf splicing in hepatocellular carcinoma development. RNA. 20: 505-15.
 
Patents
Rotem Karni. Splicing Factor Activity for Detecting and Treating Cancer (2009), Yissum, (Registered in the US/EU).
 
Avraham Maimon, Rotem Karni. Diagnosis and treatment of cancer by detection of, or manipulation of the expression of MKNK2 splicing isoforms. (2012). Provisional submitted in the US/EU
 
Vered Ben Hur, Rotem Karni. S6K as diagnostic marker for cancer, as a target for anti cancer therapy and as an indicator for response to anti-cancer drugs. (2012). Provisional submitted in the US/EU
 
Rotem Karni. Use of the levels of splicing factor SRSF6 for diagnosis and prognosis and its inhibition for treatment of cancer and Inflammatory bowel disease (IBD). (2012). Provisional submitted in the US/EU
 
Regina Golan-gerstl, Rotem Karni. Decoy Oligonucleotides for the Treatment of Diseases. (2014), Yissum, provisional patent submitted in the US/EU.
 
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