Leonard Girnita

Principal Researcher | Docent
Visiting address: J6:20 BioClinicum, Akademiska stråket 1, 17164 Solna
Postal address: K7 Onkologi-Patologi, K7 Forskning Girnita, 171 77 Stockholm

About me

  • Associate Professor of Pathology
    Research group leader
    Senior Consultant Clinical Pathology
    *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 [1]
    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 [2]
    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 [3]
    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 [4]
    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 [5]
    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 [6]
    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 [7]
    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 [8]
    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 [9]
    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 [10]
    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 [11]
    *GIRNITA LCORR*, Orega A, Sahlin S, Seregard S
    Malignant Orbital Solitary Fibrous Tumor Acta Ophthalmol. 2008 Sep 24. PMID:
    18823286 View in Medline [12]
    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 [13]
    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
    [14]
    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
    [15]
    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 [16]
    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 [17]
    *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 [18]
    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 [19]
    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
    [20]
    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 [21]
    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 [22]
    *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
    [23]
    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
    [24]
    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 [25]
    *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 [26]
    *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
    [27]
    *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 [28]
    *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
    [29]
    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 [30]
    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 [31]
    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 [32]
    *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
    [33]
    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
    [34]
    *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
    [35]
    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 [36]
    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 [37]
    *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 [38]
    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 [39]
    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
    [1] https://pubmed.ncbi.nlm.nih.gov/34785779/
    [2] https://pubmed.ncbi.nlm.nih.gov/33158816/
    [3] http://www.ncbi.nlm.nih.gov/pubmed/32805281?otool=karolib&;tool=karolinska
    [4] http://www.ncbi.nlm.nih.gov/pubmed/31434680?otool=karolib&;tool=karolinska
    [5] http://www.ncbi.nlm.nih.gov/pubmed/29567676?otool=karolib&;tool=karolinska
    [6] http://www.ncbi.nlm.nih.gov/pubmed/28581517?otool=karolib&;tool=karolinska
    [7] http://www.ncbi.nlm.nih.gov/pubmed/28092675?otool=karolib&;tool=karolinska
    [8] http://www.ncbi.nlm.nih.gov/pubmed/23188799?otool=karolib&;tool=karolinska
    [9] http://www.ncbi.nlm.nih.gov/pubmed/22509025?otool=karolib&;tool=karolinska
    [10] http://www.ncbi.nlm.nih.gov/pubmed/21685939?otool=karolib&;tool=karolinska
    [11] http://www.ncbi.nlm.nih.gov/pubmed/20150364?otool=karolib&;tool=karolinska
    [12] http://www.ncbi.nlm.nih.gov/pubmed/18823286?otool=karolib&;tool=karolinska
    [13] http://www.ncbi.nlm.nih.gov/pubmed/19302825?otool=karolib&;tool=karolinska
    [14] http://www.ncbi.nlm.nih.gov/pubmed/18576606?otool=karolib&;tool=karolinska
    [15] http://www.ncbi.nlm.nih.gov/pubmed/18632619?otool=karolib&;tool=karolinska
    [16] http://www.ncbi.nlm.nih.gov/pubmed/17828296?otool=karolib&;tool=karolinska
    [17] http://www.ncbi.nlm.nih.gov/pubmed/18070930?otool=karolib&;tool=karolinska
    [18] http://www.ncbi.nlm.nih.gov/pubmed/17303558?otool=karolib&;tool=karolinska
    [19] http://www.ncbi.nlm.nih.gov/pubmed/16407828?otool=karolib&;tool=karolinska
    [20] http://www.ncbi.nlm.nih.gov/pubmed/16489097?otool=karolib&;tool=karolinska
    [21] http://www.ncbi.nlm.nih.gov/pubmed/16166596?otool=karolib&;tool=karolinska
    [22] http://www.ncbi.nlm.nih.gov/pubmed/16046527?otool=karolib&;tool=karolinska
    [23] http://www.ncbi.nlm.nih.gov/pubmed/15878855?otool=karolib&;tool=karolinska
    [24] http://www.ncbi.nlm.nih.gov/pubmed/16000560?otool=karolib&;tool=karolinska
    [25] http://www.ncbi.nlm.nih.gov/pubmed/14729630?otool=karolib&;tool=karolinska
    [26] http://www.ncbi.nlm.nih.gov/pubmed/12821780?otool=karolib&;tool=karolinska
    [27] http://www.ncbi.nlm.nih.gov/pubmed/11016658?otool=karolib&;tool=karolinska
    [28] http://www.ncbi.nlm.nih.gov/pubmed/10980604?otool=karolib&;tool=karolinska
    [29] http://www.ncbi.nlm.nih.gov/pubmed/32457114?otool=karolib&;tool=karolinska
    [30] http://www.ncbi.nlm.nih.gov/pubmed/31847392?otool=karolib&;tool=karolinska
    [31] http://www.ncbi.nlm.nih.gov/pubmed/31600876?otool=karolib&;tool=karolinska
    [32] http://www.ncbi.nlm.nih.gov/pubmed/29776602?otool=karolib&;tool=karolinska
    [33] http://www.ncbi.nlm.nih.gov/pubmed/27378760?otool=karolib&;tool=karolinska
    [34] http://www.ncbi.nlm.nih.gov/pubmed/27988500?otool=karolib&;tool=karolinska
    [35] https://link.springer.com/protocol/10.1007/978-1-4939-3798-1_7
    [36] http://www.ncbi.nlm.nih.gov/pubmed/25964779?otool=karolib&;tool=karolinska
    [37] http://www.ncbi.nlm.nih.gov/pubmed/25466906?otool=karolib&;tool=karolinska
    [38] http://www.ncbi.nlm.nih.gov/pubmed/24276851?otool=karolib&;tool=karolinska
    [39] http://default/diss.kib.ki.se/2002/91-7349-307-4/thesis.pdf

Research

  • 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

  • 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

Articles

All other publications

Employments

  • Principal Researcher, Department of Oncology-Pathology, Karolinska Institutet, 2022-

Degrees and Education

  • Docent, Karolinska Institutet, 2008
  • Doctor Of Philosophy, Department of Oncology-Pathology, Karolinska Institutet, 2002

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