Kari J Kurppa

Kari J Kurppa
University of Turku | UTU · Institute of Biomedicine

PhD

About

43
Publications
5,667
Reads
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Introduction
My laboratory aims to understand the means cancer cells use to develop resistance to cancer therapies. Our special focus are the mechanisms that enable the establishment of minimal residual disease, or govern the maintenance of residual tumors following targeted cancer therapy. The overarching goal of our research is to develop rational combination strategies that will extend the long-term efficacy of clinically used cancer therapies.
Additional affiliations
January 2016 - present
Dana-Farber Cancer Institute
Position
  • PostDoc Position
September 2008 - December 2016
University of Turku
Position
  • PostDoc Position
Description
  • PhD December 2014, thesis titled "ERBB4 mutations in cancer and amyotrophic lateral sclerosis"

Publications

Publications (43)
Article
Activating mutations and copy number variations in ERBB genes have been shown to serve as oncogenic driver mutations and predictive biomarkers for ERBB inhibitor drugs. To address whether mutations in ERBB3 can affect the potential of ERBB3 to promote growth or affect sensitivity to ERBB inhibitors, we set up an unbiased functional screen for ERBB3...
Article
Introduction: Cancer tissues harbor thousands of mutations, and a given oncogene may be mutated at hundreds of sites across different samples. The discovery of most of the currently known driver mutations has been facilitated by their accumulation in mutation hotspots within their respective genes. However, a vast majority of mutations in cancer ti...
Article
Full-text available
Epidermal growth factor receptor (EGFR) therapy using small-molecule tyrosine kinase inhibitors (TKIs) is initially efficacious in patients with EGFR-mutant lung cancer, although drug resistance eventually develops. Allosteric EGFR inhibitors, which bind to a different EGFR site than existing ATP-competitive EGFR TKIs, have been developed as a stra...
Article
Clear cell squamous cell carcinoma (CCSCC), where cells show abundant clear cytoplasm, is a variant of squamous cell carcinoma (SCC) and a rare entity in the oral cavity. The characteristics of CCSCC, especially in immunohistochemical features, remain unclear. We characterized a case of CCSCC arising from the oral mucosal epithelium of tongue, wher...
Article
Full-text available
Despite the relatively high frequency of somatic ERBB4 mutations in various cancer types, only a few activating ERBB4 mutations have been characterized, primarily due to lack of mutational hotspots in the ERBB4 gene. Here, we utilized our previously published pipeline, an in vitro screen for activating mutations, to perform an unbiased functional s...
Article
Ameloblastoma is an odontogenic neoplasm characterized by slow intraosseous growth with progressive jaw resorption. Recent reports have revealed that ameloblastoma harbours an oncogenic BRAF V600E mutation with mitogen‐activated protein kinase (MAPK) pathway activation and described cases of ameloblastoma harbouring a BRAF V600E mutation in which p...
Conference Paper
Activating mutations and copy number variations in ERBB genes have been identified in several cancer types, and a number of cancer drugs targeting ERBB receptors have been approved for clinical use. These drugs include monoclonal antibodies (mAb) that selectively target either EGFR (ERBB1) or ERBB2 (HER2), and tyrosine kinase inhibitors (TKI) that...
Conference Paper
p>Hundreds of somatic ERBB4 mutations have been described in cancer tissues with very limited information about their functional significance. However, analyses of individual mutants have indicated that activating ERBB4 mutations, such as ERBB4 K935I, do exist. Understanding the functional consequences of ERBB4 mutations is needed in order to asses...
Conference Paper
Cancer tissues harbor thousands of mutations, and a given oncogene may be mutated at hundreds of sites across different samples. Most of these somatic mutations are expected to be inconsequential passenger mutations that reflect the general instability of the tumors. The discovery of most of the currently known driver mutations has been facilitated...
Article
Full-text available
Activating somatic mutations of the epidermal growth factor receptor (EGFR) are frequently implicated in non-small cell lung cancer (NSCLC). While L858R and exon 19 deletion mutations are most prevalent, exon 20 insertions are often observed in NSCLC. Here, we investigated the structural implications of two common EGFR exon 20 insertions in NSCLC,...
Article
While targeted therapies can be effective for a subgroup of patients, identification of individuals who benefit from the treatments is challenging. At the same time, the predictive significance of the vast majority of the thousands of mutations observed in the cancer tissues remains unknown. Here, we describe the identification of novel predictive...
Article
Certain Protein Phosphatase 2A (PP2A) complexes are human tumor suppressors. In contrast, a paper in this issue of Cancer Cell and two other recent studies demonstrate that PP2A-STRN3/4 complexes inactivate Hippo tumor suppressor pathway, resulting in YAP activation and tumorigenesis. Furthermore, this new oncogenic phosphatase mechanism may be dru...
Article
Full-text available
ERBB4 is a member of the epidermal growth factor receptor (EGFR)/ERBB subfamily of receptor tyrosine kinases that regulates cellular processes including proliferation, migration, and survival. ERBB4 signaling is involved in embryogenesis and homeostasis of healthy adult tissues, but also in human pathologies such as cancer, neurological disorders,...
Article
Eradicating tumor dormancy that develops following epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment of EGFR-mutant non-small cell lung cancer, is an attractive therapeutic strategy but the mechanisms governing this process are poorly understood. Blockade of ERK1/2 reactivation following EGFR TKI treatment by combine...
Article
TP53 , which encodes the tumor suppressor p53, is the most frequently mutated gene in human cancer. The selective pressures shaping its mutational spectrum, dominated by missense mutations, are enigmatic, and neomorphic gain-of-function (GOF) activities have been implicated. We used CRISPR-Cas9 to generate isogenic human leukemia cell lines of the...
Conference Paper
Cancer tissues harbor thousands of mutations, and a given oncogene may be mutated at hundreds of sites. Most of these somatic mutations are expected to be inconsequential passenger mutations that reflect the general instability of the tumors. The discovery of most of the currently known driver mutations has been facilitated by their accumulation in...
Article
Full-text available
Cancer tissues harbor thousands of mutations, and a given oncogene may be mutated at hundreds of sites. Yet, only a few of these mutations have been functionally tested. Here, we describe an unbiased platform for the functional characterization of thousands of variants of a single receptor tyrosine kinase (RTK) gene in a single assay. Our in vitro...
Article
Full-text available
BRAF V600E is the most common mutation in conventional ameloblastoma (AM) of the mandible. In contrast, maxillary AMs appear to harbor more frequently RAS, FGFR2, or SMO mutations. Unicystic ameloblastoma (UAM) is considered a less aggressive variant of ameloblastoma, amenable to more conservative treatment, and classified as a distinct entity. The...
Article
Full-text available
Introduction: Cancer tissues harbor thousands of mutations while the current list of clinically validated actionable variants contains only about a dozen genetic markers. Most of the somatic mutations in cancer are expected to be inconsequential passenger mutations that reflect the general instability of the tumors. The discovery of most of the cur...
Article
Genes encoding the ErbB receptor tyrosine kinases (EGFR/ERBB1, ERBB2, ERBB3, and ERBB4) are key regulators of cellular proliferation, survival, and differentiation, and thus represent potent proto-oncogenes. In particular, mutations or copy number variations of EGFR or ERBB2 are present in human malignancies and serve as predictive markers for targ...
Article
Recent efforts to comprehensively characterize the mutational landscape of non-small cell lung cancer have identified frequent mutations in the receptor tyrosine kinase ERBB4. However, the significance of mutated ERBB4 in non-small cell lung cancer remains elusive. Here, we have functionally characterized nine ERBB4 mutations previously identified...
Article
Full-text available
IntroductionHuman Epidermal Growth Factor Receptor (ERBB4/HER4) belongs to the Epidermal Growth Factor receptor/ERBB family of receptor tyrosine kinases. While ERBB1, ERBB2 and ERBB3 are often overexpressed or activated in breast cancer, and are oncogenic, the role of ERBB4 in breast cancer is uncertain. Some studies suggest a tumor suppressor role...
Article
The aim of the study was to characterize the molecular relationship between ameloblastoma and keratocystic odontogenic tumor (KCOT) by means of a genome-wide expression analysis. Total RNA from 27 fresh tumor samples of 15 solid/multicystic intraosseous ameloblastomas and 12 sporadic KCOTs was hybridized on Affymetrix whole genome arrays. Hierarchi...
Article
Full-text available
A number of genetic variants have been linked to increased risk of breast cancer. Little is, however, known about the prognostic significance of hereditary factors. Here, we investigated the frequency and prognostic significance of two ERBB4 promoter region variants, -782G>T (rs62626348) and -815A>T (rs62626347), in a cohort of 1010 breast cancer p...
Article
Full-text available
Ameloblastoma is a benign but locally infiltrative odontogenic neoplasm. Although ameloblastomas rarely metastasise, recurrences together with radical surgery often result in facial deformity and significant morbidity. Development of non-invasive therapies has been precluded by a lack of understanding of the molecular background of ameloblastoma pa...
Data
Clinical information for KCOT patients and normal sample donors.
Data
Primer and probe sequences used in real-time RT–PCR and targeted cDNA sequencing.
Data
Real-time RT–PCR analysis of the expression of ERBB4 receptor isoforms in ameloblastoma, keratocystic odontogenic tumour (KCOT) and normal oral mucosa.
Article
Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder characterized by the degeneration of motor neurons and typically results in death within 3-5 years from onset. Familial ALS (FALS) comprises 5%-10% of ALS cases, and the identification of genes associated with FALS is indispensable to elucidating the molecular pathogenesis....
Article
Full-text available
ErbB4 is a receptor tyrosine kinase that can signal by a mechanism involving proteolytic release of intracellular and extracellular receptor fragments. Proteolysis-dependent signaling of ErbB4 has been proposed to be enhanced in breast cancer, mainly based on immunohistochemical localization of intracellular epitopes in the nuclei. To more directly...
Data
Supplemental materials and methods for biotinylation of mAb 1482, sandwich ELISA for ErbB4 ectodomain, plasmid constructs, preparation of the 1479 Fab and the sErbB4:1479 Fab complex, crystallization and X-ray data collection, and structure determination and refinement. (DOC)
Data
Supplemental table showing X-ray data collection. (DOC)
Article
Genes encoding the ErbB receptor tyrosine kinases (EGFR/ERBB1, ERBB2, ERBB3, and ERBB4) are key regulators of cellular proliferation, survival, and differentiation, and thus represent potent proto-oncogenes. In particular, mutations or copy number variations of EGFR or ERBB2 are present in human malignancies and serve as biomarkers for targeted the...
Article
Full-text available
The significance of ErbB4 in tumor biology is poorly understood. The ERBB4 gene is alternatively spliced producing juxtamembrane (JM-a and JM-b) and cytoplasmic (CYT-1 and CYT-2) isoforms. Here, signaling via the two alternative ErbB4 JM isoforms (JM-a CYT-2 and JM-b CYT-2) was compared. Fibroblasts expressing ErbB4 JM-a demonstrated enhanced ErbB4...
Article
Full-text available
Cancer drugs targeting ErbB receptors, such as epidermal growth factor receptor and ErbB2, are currently in clinical use. However, the role of ErbB4 as a potential cancer drug target has remained controversial. Recently, somatic mutations altering the coding region of ErbB4 were described in patients with breast, gastric, colorectal, or non-small c...

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