Leonard Girnita
Principal researcher
About me
Associate Professor of Pathology
Research group leader
Senior Consultant Clinical Pathology
Research description
Major research interest: Cellular and molecular tumor pathology with main focus on signalling pathways downstream plasma membrane receptors. I am leading the receptor/signaling pathology research group at Karolinska Institutet, performing basic, translational and clinical research by investigating the molecular properties and regulatory mechanisms that control the function of plasma membrane receptors under normal and pathological circumstances. The final goal is to determine potential utility of the signalling complexes involved in the RTKs-GPCR cross-talk as biomarkers or molecular targets in cancer.
Teaching portfolio
Supervision of PhD students as main supervisor: 9 (Completed 5, ongoing 4)
Supervision of PhD students as co-supervisor : 9 (Completed 7, ongoing 2)
Completed and ongoing supervision of post-docs: 11
Supervisor for exchange PhD students: 9
Supervision of degree project work for the first cycle education (Bachelor's) and second cycle education (Master's) >25
Education
1995 MD License, Craiova Medical University, Romania
1999 Board Certified Specialist in Anatomic and Surgical Pathology, Romania
2002 Ph.D. in Pathology, Cytology and Experimental Pathology, Karolinska Institutet, Stockholm, Sweden
Thesis title: Growth factor pathways in human cancer. Functional and therapeutic implications http://diss.kib.ki.se/2002/91-7349-307-4/thesis.pdf
Supervisor: Olle Larsson
2007 Board Certified Specialist (Specialist läkare) in Clinic Pathology, Sweden
2008 Associate Professor (Docent) of Pathology, Karolinska Institutet, Sweden.
2015 Senior Consultant Pathology (Överläkare Klinisk Patologi), St Eriks Eye Hospital, Stockholm, Sweden
Academic honours, awards and prizes
SELECTED ACADEMIC DISTINCTIONS AND OTHER MERITS
• Young investigator award, Cancer Centrum Karolinska, KI 2000.
• Young investigator award ( “Satsning på juniora forskare” KI) 2003.
• American Association for Cancer Research-Pezcoller Foundation Scholar-in-Training Award 2005
• European Association for Cancer Research (EACR), Young Cancer Researcher “Highly Commended” Award 2005
• Young investigator award (“Satsning på juniora forskare” KI) 2006
• ”Alex och Eva Wallströms stiftelse för vetenskaplig forskning och utbilding” Award (Three times, 2005, 2006 and 2007)
• Young Investigator award, 6 years position from Swedish Cancer Society, 2006-12
• Visiting professor, Department of Life Science, Tokyo University, Japan (2012)
• EACR Honorary Life Membership and Board consultant, for exceptional service in furthering the aims, objectives and activities of the association (2018).
• Half-time Position in Clinical Research Environment from Swedish Research Council (VR) 2013-2018
• Senior Clinical Investigator Award, Swedish Cancer Society 2019-2025
Selected Publications
Selected Original Peer-Reviewed Publications
Song D, Cismas S, Crudden C, Trocme E, Worrall C, Suleymanova N, Zheng H, Seregard S, Girnita A and GIRNITA L
IGF-1R is a molecular determinant for response to p53 reactivation therapy in conjunctival melanoma
Oncogene. 2022 Jan;41(4):600-611. PMID: 34785779
Crudden C, Takashi S, Song D, Dragomir MP, Cismas S, Serly J, Nedelcu D, Fuentes-Mattei, Tica A, Calin GA, Girnita A and GIRNITA L
Inhibition of G protein-coupled receptor kinase 2 promotes unbiased downregulation of IGF-1 receptor and restrains malignant cell growth
Cancer Research 2021 DOI: 10.1158/0008-5472. PMID: 33158816
Chen B, Dragomir M, Fabris L, Bayraktar R, Knutsen E, Liu X, Tang C, Li Y, Shimura T, Ivkovic T, De los Santos M, Anfossi S, Shimizu M, Shah M, Ling H, Shen P, Multani A, Pardini B, Burks J, Katayama H, Reineke L, Ferracin M, Oki E, Fromm B, Ivan C, Bhuvaneshwar K, Gusev Y, Menter D, Sen D, Matsuyama T, Uetake H, Vasilescu C, Parker-Thornburg J, Taguchi A, Hanash S, Girnita L, Slaby S, Goel A, Varani G, Gagea M, Li1 C, Ajani J and Calin GA
The lncRNA CCAT2 induces chromosomal instability through the BOP1 – AURKB axis
Gastroenterology 2020 Aug 14; PMID: 32805281
Fabbri M*, Girnita L*, Varani G, Calin GA
Decrypting non-coding RNA interactions, structures and functional networks
Genome Research 2019 Sep;29(9):1377-1388. * equal contribution PMID: 31434680
Shah, MY, Pilecki V, Ferracin M, Redis R, Fabris L, Zhang X, Shimizu S, Rodriguez-Aguayo C, Almeda MI, Ciccone M, Nedelcu D, Cortez MA, Ivan C, Manshouri T, Calin S, Muftuoglu M, Banerjee PP, Badiwi MH, Parker-Thornburg J, Multani A, Welsh JW, Estecio MR, Ling H, Tomuleasa C ,Delia Dima D, Yang H, You J, Radovich M, Shpall E, Rezvani K, Fabbri M, GIRNITA L, Berindan-Neagoe I, Verstovsek S, Fodde R, Bueso-Ramos C, Gagea M, Manero GG, Calin GA
Cancer-associated rs6983267 SNP and its accompanying long non-coding RNA CCAT2 induce myeloid malignancies via unique SNP-specific RNA mutations
Genome Res. 2018 Apr;28(4):432-447. PMID: 29567676
Suleymanova S, Crudden C, Takashi S, Worrall C, Oprea I, Tica A, Calin GA, Girnita A, and GIRNITA L
Functional antagonism of β-arrestin isoforms balance IGF-1R expression and signaling with distinct cancer-related biological outcomes
Oncogene. 2017 Jun 5. doi: 10.1038/onc.2017.179. PMID: 28581517 View in Medline
Claire Worrall, Suleymanova N, Crudden C, Trocoli Drakensjö I, Candrea E, Nedelcu D, Takahashi SI, Girnita LCORR, Girnita A.
Unbalancing p53/Mdm2/IGF-1R axis by Mdm2 activation restrains the IGF-1-dependent invasive phenotype of skin melanoma.
Oncogene 2017 36;23 3274-3286 View in Medline
Zheng H, Shen H, Oprea I, Worrall C, Stefanescu R, Girnita A, GIRNITA L
β-Arrestin-biased agonism as the central mechanism of action for insulin-like growth factor 1 receptor-targeting antibodies in Ewing's sarcoma.
Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20620-5. PMID: 23188799 View in Medline
Huiyuan Zheng, Claire Worrall, Shen Hongchang, Tarik Isaad, Stefan Seregard, Ada Girnita and GIRNITA L
Selective recruitment of G protein coupled receptor kinases (GRKs) controls signaling and trafficking of the Insulin-like Growth Factor 1 Receptor
Proc Natl Acad Sci U S A. 2012 May 1;109(18):7055-60. PMID: 22509025 View in Medline
Girnita A, Zheng H, Grönberg A, GIRNITA L, and Ståhle M
Identification of the cathelicidin peptide LL-37 as agonist for the type I Insulin-like Growth Factor Receptor
Oncogene 31: 2012 Jan 3. 352-365 PMID: 21685939 View in Medline
Yin S, Girnita A, Axelson M, Nister M, Larsson O, Strömberg T , GIRNITA L. Targeting of IGF-1 receptor by picropodophyllin (PPP) in glioblastoma.
Neuro Oncol. 2010 Jan;12(1):19-272010. PMID: 20150364 View in Medline
GIRNITA LCORR, Orega A, Sahlin S, Seregard S
Malignant Orbital Solitary Fibrous Tumor Acta Ophthalmol. 2008 Sep 24. PMID: 18823286 View in Medline
Natalishvili N, Vasilcanu D, Axelson O, GIRNITA L, Larsson O
Aberrant intracellular IGF-1R β-subunit makes receptor knockout cells (IGF1R-/-) susceptible to oncogenic transformation
Experimental Cell Research, 2009 May 1;315(8):1458-67. PMID: 19302825 View in Medline
Vitale M, Prestat G, Lopes D, Madec D, Kammerer C, Poli G, GIRNITA L.
New picropodophyllin analogs via palladium-catalyzed allylic alkylation-Hiyama cross-coupling sequences.
J Org Chem. 2008 Aug 1;73(15):5795-805. PMID: 18576606 View in Medline
Sehat B, Andersson S, GIRNITA LCORR and Larsson O
Identifcation of c-Cbl as a new ligase for IGF-1R with distinct roles to Mdm2 in receptor ubiquitination and endocytosis.
Cancer Research 2008 Jul 15;68(14):5669-77. PMID: 18632619 View in Medline
Vasilcanu R ,Vasilcanu D, Rosengren L, Natalishvili N, Sehat B, Yin S, Girnita A, Axelson M, GIRNITA LCORR, Larsson O.
Picropodophyllin induces downregulation of the insulin-like growth factor 1 receptor. Potential mechanistic involvement of Mdm2 and β-arrestin1
Oncogene 2008 Mar 6;27(11):1629-38. PMID: 17828296 View in Medline
Vasilcanu R ,Vasilcanu D, Sehat B, Yin S, Girnita A, Axelson M, and GIRNITA L.
Insulin-like growth factor type-I receptor (IGF-1R) dependent phosphorylation of ERK1/2 but not Akt (PKB) can be induced by picropodophyllin.
Mol Pharmacol. 2008 May;73:930-9. PMID: 18070930 View in Medline
GIRNITA LCORR, Shenoy S, Vasilcanu D, Girnita A, Lefkowitz RJ and Larsson O.
Mdm2 mediate IGF-1 receptor stimulated ERK activation and cell cycle progression
J Biol Chem. 2007 Apr 13;282(15):11329-38. PMID: 17303558 View in Medline
Vasilcanu D, Girnita A, Axelson M, Larsson C, Larsson O and GIRNITA L
The insulin-like growth factor-1 receptor inhibitor PPP produces only very limited resistance in tumor cells exposed to long-term selection.
Oncogene. 2006 May 25;25(22):3186-95. PMID: 16407828 View in Medline
Girnita A , All-Ericsson C, , Seregard S, Axelson M, Larsson O and GIRNITA L
The insulin-like growth factor-1 receptor (IGF-1R) inhibitor PPP blocks uveal melanoma cell and tumor growth: Implications for a new treatment regimen.
Clin Cancer Res. 2006 Feb 15;12(4):1383-91. PMID: 16489097 View in Medline
Stromberg T, Ekman S, GIRNITA L, Larsson O, Axelson M, Lennartsson J, Hellman U, Vanderkerken K, Carlson K, Österborg A, Vanderkerken K, Nilsson K, Jernberg-Wiklund H. IGF-I receptor tyrosine kinase inhibition by the cyclolignan PPP induces G2 cell cycle accumulation and apoptosis in multiple myeloma cells.
Blood. 2006 Jan 15;107(2):669-78. PMID: 16166596 View in Medline
Menu E, Jernberg Wiklund H, Stromberg T, De Raeve H, GIRNITA L, Larsson O, Axelson M, Asosingh K, Nilsson K, Van Camp B and Vanderkerken K.
Effects of inhibition of the IGF-1 receptor tyrosine kinase in multiple myeloma: an in vitro and in vivo study on the 5T33MM Mouse Model.
Blood. 2006 Jan 15;107(2):655-60. PMID: 16046527 View in Medline
GIRNITA L, Shenoy S, Sehat B, Vasilcanu R, Girnita A, Lefkowitz RJ, Larsson O.
Beta-arrestin is required for Mdm2 dependent IGF-1R ubiquitination.
J Biol Chem. 2005 Jul 1;280(26):24412-9. PMID: 15878855 View in Medline
Ulfarsson E, Karström A, Girnita A, Vasilcanu D, Thoren M, Kratz G, Hilman J, Axelson M, Larsson O, GIRNITA L.
Expression and growth dependency of the insulin-like growth factor I receptor in craniopharyngioma cells: a novel therapeutic approach.
Clin Cancer Res. 2005 Jul 1;11(13):4674-80. PMID: 16000560 View in Medline
Girnita A *, GIRNITA L *, Prete Fd F, Bartolazzi A, Larsson O, Axelson M.
Cyclolignans as Inhibitors of the Insulin-Like Growth Factor-1 Receptor and Malignant Cell Growth.
Cancer Res. 2004 Jan 1; 64(1): 236-242. PMID: 14729630* Equal contribution View in Medline
GIRNITA L, Girnita A, Larsson O.
Mdm2-dependent ubiquitination and degradation of the insulin-like growth factor 1 receptor.
Proc Natl Acad Sci U S A. 2003 Jul 8; 100(14): 8247-52. PMID: 12821780 View in Medline
GIRNITA L, Girnita A, Brodin B, Xie Y, Nilsson G, Dricu A, Lundeberg J, Wejde J, Bartolazzi A, Wiman KG, Larsson O.
Increased expression of insulin-like growth factor I receptor in malignant cells expressing aberrant p53: functional impact.
Cancer Res. 2000 Sep 15; 60(18): 5278-83. PMID: 11016658 View in Medline
GIRNITA L, Girnita A, Wang M, Meis-Kindblom JM, Kindblom LG, Larsson O.
A link between basic fibroblast growth factor (bFGF) and EWS/FLI-1 in Ewing's sarcoma cells.
Oncogene. 2000 Aug 31; 19(37): 4298-301. PMID: 10980604 View in Medline
Selected reviews and book chapters
Crudden C and Girnita L.
The tale of a tail: The secret behind IGF-1R’s oncogenic power
Sci Signal. 2020 May 26;13(633):eabb7887. PMID: 32457114 View in Medline
Chen B, Li J, Chi D, Sahnoune I, Calin S, Girnita L, Calin GA
Non-Coding RNAs in IGF-1R Signaling Regulation: The Underlying Pathophysiological Link between Diabetes and Cancer.
Cells. 2019 Dec 14;8(12):1638. doi: 10.3390/cells8121638. PMID: 31847392 View in Medline
Crudden C, Song D, Cismas S, Trocmé E, Pasca S, Calin GA, Girnita A, Girnita L.
Below the Surface: IGF-1R Therapeutic Targeting and Its Endocytic Journey.
Cells. 2019 Oct 9;8(10). pii: E1223. PMID: 31600876 View in Medline
Crudden C, Shibano T, Song D, Suleymanova N, Girnita A, Girnita L.
Blurring Boundaries: Receptor Tyrosine Kinases as functional G Protein-Coupled
Int Rev Cell Mol Biol. 2018;339:1-40. PMID: 29776602 View in Medline
Girnita L, Takahashi SI, Crudden C, Fukushima T, Worrall C, Furuta H, Yoshihara H, Hakuno F and Girnita A
When phosphorylation encounters ubiquitination: a balanced perspective on IGF1R signalling
Prog Mol Biol Transl Sci. 2016;141:277-311. PMID: 27378760 View in Medline
Ling H, Girnita L, Buda O, Calin GA.
Non-coding RNAs: the cancer genome dark matter that matters!
Clin Chem Lab Med. 2017 May 1;55(5):705-714. PMID: 27988500 View in Medline
Girnita L, Girnita A and Crudden C
Differential regulation of IGF-1 and Insulin signaling by GRKs
Book chapter in: Gurevich and J. Tesmer(eds.), G Protein-Coupled Receptor Kinases, Advances in Biochemistry in Health and Disease, © Springer Science+Business Media New York 2016 ISBN 978-1-4939-3796-7 https://link.springer.com/protocol/10.1007/978-1-4939-3798-1_7
Crudden C, Girnita A, and Girnita L
Targeting the IGF-1R: The Tale of The Tortoise and The Hare
Front Endocrinol (Lausanne). 2015 Apr 27;6:64. PMID: 25964779 View in Medline
Crudden C, Ilic M, Suleymanova N, Worrall C, Girnita A, Girnita L.
The dichotomy of the Insulin-like growth factor 1 receptor: RTK and GPCR: friend or foe for cancer treatment?
Growth Horm IGF Res. 2014 doi: 10.1016/j.ghir.2014.10.002. PMID: 25466906 View in Medline
Girnita L, Worrall C, Takahashi SI, Seregard S, Girnita A
Something old, something new and something borrowed: Emerging paradigm of insulin-like growth factor type 1 receptor (IGF-1R) signaling regulation.
Cell Mol Life Sci. 2013 Nov 26. PMID: 24276851 View in Medline