BioMediTech Research Groups

Cancer Signaling

Group Leader: Academy Research Fellow Daniela Ungureanu

daniela.ungureanu(at)uta.fi

About Us

Our research focuses on understanding the role of ROR family of pseudokinases in promoting or sustaining malignant transformation. We aim to characterize the structural and functional properties of ROR1 and ROR2 and define the molecular networks employed by this family of proteins in normal and pathological conditions. In collaboration with clinical researchers, we aim to characterize potential biomarkers for cancer therapies and seek to identify small molecule inhibitors that target ROR functions in human diseases.

Research interests and expertise

Our research interest focuses on the following strategies:

  • to assess ROR pseudokinases intracellular signaling pathways and evaluate their survival role in various cancer models such as hematological malignancies (lymphoma and leukemia) and ovarian cancer, both in cell-lines and patients samples
  • to explore combinatorial therapies and drug-resistant models by performing DSRT (drug-sensitivity and resistance testing) in order to identify novel therapeutic strategies by targeting ROR pseudokinases
  • to identify ROR1 small molecule inhibitors and test their efficacy in vitro and in relevant preclinical models

The long-term goal is to implement this information in developing better therapeutic strategies for treatment of cancer or other diseases.

Expertise:

  • recombinant protein production using Baculo-system
  • purification, analysis and biochemical characterization of recombinant kinases and pseudokinases
  • analysis of protein expression and intracellular signaling cascade of receptor proteins in different cancer models
  • short-term and long-term culture of patient samples (lymphoma/leukemia)
  • DSRT screening for lymphoma cell lines and patients samples

Collaboration offer and requests

We are eager to collaborate with research groups interested in cancer signaling (leukemia/lymphoma and ovarian cancer), drug-screening and ex in-vivo culture of patients samples. We would like to collaborate with clinical researchers involved in studying ovarian cancer, mantle cell lymphoma and chronic lymphocytic leukemia.

Major Publications

  1. Karvonen H, Chiron D, Niininen W, Ek S, Jerkeman M, Moradi E, Nykter M, Heckman CA, Kallioniemi O,  Murumägi A, Ungureanu D. Crosstalk between ROR1 and BCR pathways defines novel treatment strategies in mantle cell lymphoma. Blood Advances. 1:2257-2268, 2017
  2. Hammarén HM, Ungureanu D, Grisouard J, Skoda RC, Hubbard SR, Silvennoinen O. ATP binding to the pseudokinase domain of JAK2 is critical for pathogenic activation. PNAS 112(15):4642-7, 2015. IF: 9.7
  3. Shan Y, Gnanasambandan K, Ungureanu D, Kim ET, Hammarén H, Yamashita K, Silvennoinen O, Shaw DE, Hubbard SR. Molecular basis for pseudokinase-dependent autoinhibition of JAK2 tyrosine kinase. Nature Struct. Mol. Biol. 21(7):579-84, 2014. IF: 13.3
  4. Bandaranayake RM*, Ungureanu D*, Shan Y, Shaw DE, Silvennoinen O, Hubbard SR. Crystal structures of the JAK2 pseudokinase domain and the pathogenic mutant V617F. Nature Struct. Mol. Biol. 19(8):754-9, 2012  (* equal contributions) IF: 13.3
  5. Ungureanu D, Wu J, Pekkala T, Niranjan Y, Young C, Jensen ON, Xu CF, Neubert TA, Skoda RC, Hubbard SR, Silvennoinen O. The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling. Nature Struct. Mol. Biol. 18(9):971-6, 2012. IF: 13.3
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