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 4, ongoing 5)

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 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

 

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 2020 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

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