biocare2-logo.gif Biomarkers in Cancer Medicine


Breast cancer:

Docent Magnus Abrahamsson

Lund University,  Clinical Chemistry, Dept. of Laboratory Medicine, Lund

Address: Universitetssjukhuset, 221 85 Lund

Phone: +46-46-173445

Email:  Magnus.Abrahamson@med.lu.se


Tumor entities of interest:

General tumor markers; especially breast and prostate cancer

Group members:

Ulf Ekström, MD, PhD (senior physician)

Hanna Wallin (PhD student)

jenny Apelqvist (ST-läkare, PhD student)

Anne-Cathrine Löfström (BMA)

Technologies of interest:

Protein chemsitry techniques; proteomics; enzymology methods; physical chemistry incl. protein interaction techniques; cell culture; microscopy; in situ labelling by enzyme activity probes; immunoassay methods.

Research abstract:

The Importance of Cystatin C and Other Cystatins as Regulators and Markers in Cancer.

Cystatin C is the best studied of twelve proteins forming a family of human cysteine protease inhibitors. The molecule has two independent enzyme inhibitory sites. One results in specific inactivation of the activities of papain-like cysteine proteases such as the cysteine cathepsins B, H, L and K. The other inhibitory site is directed towards the less known enzyme legumain. Much work has been done to examine the role of cysteine cathepsins in malignancies. For example, cathepsin B as well as cathepsin L levels and/or activities have been shown to be increased in various malignant diseases. Differences in intracellular distribution, surface localization and secretion of cathepsin B have also been seen in cancer cells. The ratio cathepsin B/cystatin C is altered in several cancers indicating a disturbed balance between the protease and its inhibitor. The level of legumain expression is closely connected to invasion and metastasis in breast cancer.

Although the serum level of cystatin C in cancer patients is generally not affected, the level of the complex of cathepsin B/cystatin C is lower in sera of lung cancer patients compared to sera from patients with benign lung disorders or healthy controls. Our preliminary data show that cystatin C expression is lower in tissue from metastatic prostate cancer compared to benign tissue. In addition, another cystatin with the same inhibitory capacity as cystatin C, cystatin E/M, has been reported epigenetically down-regulated by methylation in metastases of primary breast cancer. With this as a background, a major aim of the present project is to evaluate each protein in the the 12-member cystatin family of antiproteases, alongside with the 12 theoretical target enzymes (11 cysteine cathepsins and legumain), as potential diagnsotic or prognostic markers in cancer. The expression of the individual genes will be studied at the RNA level, antibody-based as

says for quantitation of the proteins and amount of protease/antiprotease complexes will be set up, and activity probes will be utilized to measure the net activity of the regulated cysteine proteases in cancer cells and tissue.

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Assistant professor Maria Alvarado Kristensson

Department of Laboratory Medicine, Malmö

Address: Lund University, Center for Molecular Pathology, SUS Malmö, Entrance 78 2nd floor,

SE-205 02, Malmö, Sweden

Phone: +46-40 338391

Email: maria.alvarado-kristensson@med.lu.se

Tumor entities of interest: 

I work with various tumor types depending on what I am studying. Currently, I work with prostate,

breast and colon cancers. I also work with small cell lung cancinoma

Group members:

Greta Höög, PHD student

Ingrid Caro-Östergren, master student

Åsa Ehlen, Post-doc

Catalina Rossello, Post-doc

Technologies of interest:

Bioinformatics, TMA, fluorescence microscopy, molecular biology


Research abstract:

Our main focus is the evaluation of SADB kinases, RBM3 and γ-tubulin as novel cancer biomarkers.

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Professor Anna Blom

Lund University, Laboratory Medicine Malmö.

Address: Lund University, Laboratory Medicine Malmö, Wallenberg Laboratory floor 4SUS Malmö, 

S-205 02 Malmö, Sweden

Phone: +46-40 -33 82 33

Email: anna.blom@med.lu.se

Tumor entities of interest: Interested in innate immune response mainly complement system interactions with tumor. 

Group members:

Marcin Okroj

Technologies of interest

Protein chemistry, protein interactions (Biacore), FACS, various kinds of microscopy.

 

Research abstract:

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Professor Carl Borrebaeck

Lund University, Department of Immunotechnology, Lund

Address: Lund University, CREATE Health, Department of Immunotechnology,

BMC D13, SE-221 84 Lund, Sweden. 

Phone: +46-46-2229613

Email: carl.borrebaeck@immun.lth.se

Tumor entities of interest:

Breast cancer, Pancreatic cancer, Ovarian cancer,Prostate cancer and Lymphoma

Group members:

www.immun.lth.se/research/immunotechnology/

Technologies of interest:

Affinity proteomics

Research abstract:

www.createhealth.lth.se

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Professor Mårten Fernö

Department of Oncology, IKVL, Lund, Lund University

Address: Lund University, Clinical Sciences Lund, Department of Oncology, Barngatan 2B, SE-221 85 Lund, Sweden

Phone: +46-46-17 75 65

Email: Marten.Ferno@med.lu.se

Tumor entities of interest:  Breast cancer

Group members:

Sara Baker

Pär-Ola Bendahl

Gunilla Chebil

Marie Klintman

Kristina Lövgren

​Carina Strand

Technologies of interest:

  • Tissue microarray and immunohistochemistry.

Research abstract: Breast cancer is the most common female malignancy in Sweden (~7000 cases/year). The disease shows a considerable variation in clinical outcome. With prognostic factors the patients are categorized into subgroups with different risk for recurrence. Generally accepted prognostic factors are distant metastases, lymph node involvement, tumor size, histological grade, patient age, human epidermal growth factor receptor type 2 (HER2), estrogen (ER) and progesterone receptor (PgR), and the proliferative marker Ki67. The choice of systemic therapy is generally based on treatment predictive factors, e.g. ER, PgR and HER2. In spite of a considerable number of histopathological and biological factors, as well as treatment modalities, a considerable proportion of the patients recur or are overtreated.

With new technology, we hope to improve the prognostic and treatment predictive instruments, currently being used in the clinical management of breast cancer. Examples of such new methods at our department are array based techniques and techniques within proteomics, tissue micro array (effective immuno histochemical technique), and detection of tumour markers and protein pattern in blood. The close collaboration between our group and the South Sweden Breast Cancer Group with different specialities, including surgery, oncology, pathology, statistics and tumor biology, is a prerequisite for the evaluation of the clinical importance of new factors. We have also access to tumor material from well characterized patient materials.

In order to avoid under- and overtreatment, improvements in the judgement of prognosis and treatment selection are necessary. Our goal is to achieve personalized therapy for patients with breast cancer.

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Docent Lena Gustavsson

Department of Laboratory Medicine, Malmö

Address: Lund University, Center for Molecular Pathology, SUS Malmö, Entrance 78 2nd floor,

SE-205 02, Malmö, Sweden

Phone: +46-40 337756

Email: Lena.Gustavsson@med.lu.se

Tumor entities of interest: 

lung cancer, neuroblastoma, breast cancer

Group members:

Technologies of interest:

Solute carrier and ABC transporter functional assays, cell biology, gene expression.

Research abstract:

Impact of drug transporters on pharmacological efficacy –

Inter-individual variation in drug response and resistance in cancer.

In the oncology area, inter-individual difference in drug response and development of drug resistance are major issues. The aim of the research is to develop our understanding of cancer drug response as related to pharmacokinetics and drug exposure at the target site. Several drug transporters (solute carriers and ATP-binding cassette transporters) work in concert to regulate the intracellular drug concentration. Their impact on the inter-individual variation in pharmacological effect is addressed to enhance future potential to improve diagnostics/prognostics and design personalized therapies. The main objectives are to

1) Identify changes in drug transporter expression in tumors related to differences in clinical outcome

2) Assess the regulation of transporter expression in tumor cells in response to drug exposure and changes in the microenvironment

3) Build a model to predict the intracellular drug concentration in tumor cells related to efficacy.


Associate Professor Ingrid Hedenfalk

Department of Oncology, Clinical Sciences, Lund University.

Address: BMC C1341a, 221 84 Lund, Sweden

Phone: +46-46-2220652

Email:  Ingrid.Hedenfalk@med.lu.se

Tumor entities of interest:

Breast Cancer, Male Breast Cancer

Group members:

Kristina Aaltonen, post doc

Anna Ebbesson, technician

Ida Johansson, PhD student

Siker Kimbung, PhD student

Technologies of interest:

Genomics, Microarrrays, Bioinformatics, Immunohistochemistry​

Research abstract: Molecular characterization of male breast cancer and early events in cancer evolution for the identification of biomarkers of clinical significance.

The overall objective of our project is to molecularly characterize male breast cancer, thereby increasing our knowledge of this rare disease, and to identify genetic changes of clinical importance that may be utilized as biomarkers. We also aim to characterize the genomic events underlying breast cancer initiation in genetically predisposed women to increase our understanding of the early steps in breast cancer evolution.

Male breast cancer is exceedingly rare, constituting <1% of all breast cancers diagnosed in Sweden annually, but reports from the US and UK indicate that the incidence has been increasing over the past 20 years. The rarity of the disease precludes any randomized trials for optimizing patient management, and tumour biological studies are hampered by small sample sizes. Hence, knowledge of the disease is limited and treatment recommendations are largely based on prior knowledge of breast cancer in women. 

We have recently applied high-resolution genomic profiling to characterize a cohort of male breast carcinomas, revealing distinct differences, in addition to similarities, compared with female breast cancer. Given the great differences in e.g. hormonal levels between males and females, this may indicate differences in cancer progression, risk factors, as well as response to treatment. We are therefore applying multiple genome-wide techniques to better characterize male breast cancer (including transcriptional profiling by microarrays, methylation profiling, miRNA profiling, immunohistochemistry and next-generation sequencing), with the aim of identifying the underlying cause/s and potentially novel treatment targets. We have access to a large cohort of well-annotated male breast cancer samples, and together with oncologists, pathologists and bioinformaticians we hope to increase our knowledge of this disease.

We have also recently described an increased frequency of copy number aberrations in histopathologically normal breast tissue from women genetically predisposed to develop breast/ovarian cancer due to mutations in the BRCA1 gene. We aim to further characterize these aberrations using high-resolution SNP-arrays, and to address whether BRCA1 and BRCA2 mutations give rise to different genomic profiles; this may pinpoint the early genetic events leading to cancer evolution in these individuals, and may also explain the different clinical and phenotypic characteristics caused by the respective genes. We are also comparing the genomic profiles in breast and ovarian tissue to identify potential aberrations in common between these target tissues.

Genome-wide studies are likely to improve our understanding of breast cancer evolution in males as well as in predisposed women, and should provide a basis for improved diagnosis, identification of treatment targets and prediction of outcome.

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Associate Professor Khalil Helou

Clinical sciences, Oncology, Sahlgrenska University Hospital

Address: Sahlgrenska Cancer Center, Medicinaregatan 1G, 6th floor, SE-413 90 Gothenburg, Sweden

Phone: (+46) 31 7866746

Email: khalil.helou@oncology.gu.se

Tumor entities of interest: 

Group members:

Khalil Helou

Toshima Parris

Emman Shubbar

Szilard Nemes

Anna Danielsson

Technologies of interest:

Microarray, Qpcr, Immunohistochemistry, Cell transfection, Nude mice, FISH

Research abstract:

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Associate Professor Helena Jernström

Department of Oncology, Clinical Sciences, Lund University

Address: Barngatan 2B, 221 85 Lund, Sweden

Phone: +46-46-17 67 19

Email: helena.jernstrom@med.lu.se

Tumor entities of interest: Breast Cancer

Group members:

Kristina Lundin

Maria Henningson

Technologies of interest:

  • Genetic epidemiology
  • Pharmacogenetics
  • Genotyping

Research abstract: More than 7000 women are diagnosed with breast cancer annually. Ten percent of all breast cancers are familial. Deleterious mutations have been identified in several genes, most notably BRCA1/2. Up to 80% of female mutation carriers develop breast cancer. Little is known about the normal function of these genes, and how breast cancer risk is modified by hormones, alterations in hormone metabolism and polymorphisms in low-penetrance genes. Moreover, up to 70% of all breast cancer patients receive adjuvant therapy unnecessarily. These patients are either already cured by surgery or the medications they receive do not work as intended.

Certain polymorphic variants are implicated in 20% of inter-individual variability in drug metabolism; hormones, growth factors and lifestyle also influence drug response and prognosis, but are currently not used for selection of therapy.

Project #1 Overview: The first project is based on a consecutive series of 2500 breast cancer patients, of which over 1000 have been enrolled so far since 2002. We investigate the prognostic significance of selected polymorphisms alone and in combination with hormone and lifestyle factors. In a collaborative pilot project with CREATE Health we are currently evaluating whether the approximately 2000 polymorphic variants in genes responsible for adsorption, distribution, metabolism and excretion of drugs on the Affymetrix DMET chip can be used for better selection of endocrine breast cancer therapy. Available registries are used for optimal follow-up of new cancers and recurrences.

Clinical Relevance: The suboptimal current criteria for the selection and administration of adjuvant breast cancer therapy, combined with the feasibility of mass genotyping and hormonal measurements, suggest that the identification of new prognostic markers may have a profound impact on the care of breast cancer patients and lead to new recommendations regarding lifestyle factors.

Project #2 Introduction: The second project is based on young healthy women from high-risk breast cancer families. We compare hormonal levels, body size and response to hormone exposure between mutation carriers and non-carriers and investigate the effects of polymorphisms in various genes. Our findings so far have confirmed our previous report of an idiosyncratic IGF-1 response in oral contraceptive users with a specific IGF1 genotype. IGF-1 is a strong predictor of early-onset breast cancer in the general population.

Clinical Relevance: This finding may therefore have future implications for the development of a predictive test to identify the subgroup of women who are at increased risk of breast cancer if they use the birth control pill.

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Professor Göran Landberg

Sahlgrenska Cancer Center, University of Gothenburg

Address: Sahlgrenska Cancer Center, University of Gothenburg, Department of Biomedicine, 405 30 Göteborg

Phone: +46768870969

Email: goran.landberg@gu.se​

Tumor entities of interest:

Breast​

Group members:

Paul Fitzpatrick

Sofie Nilsson (Lund university)

Sophie Lehn (Lund university)

Elise Nilsson (Lund university)

Christina Möller (Lund university)

Technologies of interest:

Molecular Pathology, Tissue microarray

Research abstract:

Breast cancer is a multitude of different diseases with varying behaviours and it is critical to identify subgroups with similar tumour biological properties as well as define groups that will respond to specific treatments or alternatively be targeted with novel treatment approaches. Within the project we will use a molecular pathology approach including studies of primary tumours as well as experimental models to identify novel breast cancer treatment and prevention targets and principles. We will focus on key properties of the breast cancer microenvironment and delineate how the tumour stroma will affect the coordination of proliferation and tumour infiltration as well as the response to endocrine therapies. We will further characterise the earliest stromal and epithelial changes in breast cancer progression with a focus on miRNA. Within the hypoxia project we will concentrate on how hypoxia affects the presence of cancer initiating cells and focus on our preliminary findings suggesting that breast cancer will respond differently to low oxygen. Key regulators behind this contrasting behaviour will be identified and ultimately we will identify novel inhibitors that block this process and potentially launch a therapy approach for increasing the efficiency of hypoxia inducing or angiogenic blocking therapies.


Professor Christer Larsson

Lund University, Department of Laboratory Medicine, Malmö

Address: Lund University, CMP, Entr 78, 3rd floor, SUS Malmö, 205 02 Malmö

Phone: +46-40-337404

Email: christer.larsson@med.lu.se

Tumor entities of interest:

Breast cancer

Neuroblastoma

Group members:

Katarzyna Chmielarska Masoumi

Tamae Kobayashi

Anna Schultz

Lousie Cornmark

Sofia Winslow

Technologies of interest:

Molecular and cellular biology

Research abstract:

PKC isoforms and cell death pathways as ptoential molecular targets for therapy.

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Docent Karin Leandersson

Lund University, Center f or Molecular Medicine (CMP) Department of  Laboratory Medicine,Malmö

Address: CMP, Entr 78, plan 2, SUS-Malmö, 20502 Malmö

Phone: 0702968783

Email: karin.leandersson@med.lu.se

Tumor entities of interest:

Breast cancer

Malignant melanoma

Group members:

Catharina Medrek

Caroline Bergenfelz

Verena von Bulow

Technologies of interest:

Cell sorting (MACS & FACS)

Cellular Co-culture systems

Molecular biology

In vivo models

Research abstract:

Background: In Sweden, one in ten women will be diagnosed with breast cancer during her life. The recurrence of the disease is characterized by distal metastasis and at this stage the prognosis is poor. From recent research it has become clear that the immune system definitely can distinguish the presence of a tumor and that it also is involved in the metastatic processes. Unfortunately, the involvement seems to in a suppressed state rather than in an activated anti-tumor state. The reasons to this are still unknown and models to study the mechanisms are few.

Aim: In this project I will study how metastatic processes can suppress the immune response and whether the immune system actually promotes breast cancer metastasis. Results and Planned work: This will be done using human material and by designing new mouse models of breast cancer metastasis resembling the human situation. We will focus on the immunosuppressive cell populations MDSCs, TAMs and immature antigen presenting cells.

Relevance: If one can understand what is causing the immune suppression in breast cancer this might be changed to eventually hinder the devastating progression of breast cancer metastasis.

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Professor Hakon Leffler

Lund University, ILM Lund

Address: MIG, ILM, Sölvegatan 23, SE 22362 Lund

Phone: +46706150514

Email: hakon.leffler@med.lu.se

Tumor entities of interest:

Brain tumor

Breast cancer

Gastrointestinal cancer

Gynecological cancer

Leukemia and Lymphomas

Lung cancer

Pediatric tumors

Skeletal and soft tissue cancers

Urological cancers

Other tumor entities

Group members:

Michael Carlsson

Emma Salomonsson

Adriana Lepur

John Stegmayer

Barbro Kahl-Knutson

Technologies of interest:

Affinity chromatography

FBining assay based on fluorescnece anistropy

Molecular biology and cell buiology with associated techniques

Research abstract:

Sera from 25 metastatic breast cancer patients and 25 healthy controls were subjected

to affinity chromatography using immobilized galectin-1. Serum from the healthy

subjects contained on average 1.2 mg per ml (range 0.7 - 2.2) galectin-1 binding

glycoproteins, whereas serum from the breast cancer patients contained on average

2.2 mg/ml (range 0.8 - 3.9), with a higher average for large primary tumours. The major

bound glycoproteins were α-2-macroglobulin, IgM, and haptoglobin. Both the IgM and

haptoglobin concentrations were similar in cancer compared to control sera, but the

percentage bound to galectin-1 was lower for IgM and higher for haptoglobin: about

50% (range 20-80) in cancer sera and about 30% (range 25-50 in healthy sera).

Galectin-1 binding and non-binding fractions were separated by affinity

chromatography from pooled haptoglobin from healthy sera. The N-glycans of each

fraction were analyzed by mass spectrometry and the structural differences and

galectin-1 mutants were used to identify possible galectin-1 binding sites. Galectin-1

binding and non-binding fractions were also analysed regarding their haptoglobin

function. Both were similar in forming complex with haemoglobin and mediate its

uptake into alternatively activated macrophages. However, after uptake there was a

dramatic difference in intracellular targeting, with the galectin-1 non-binding fraction

going to a LAMP-2 positive compartment (lysosomes), while the galectin-1 binding

fraction went to larger galectin-1 positive granules. In conclusion, galectin-1 detects a

new type of functional biomarker for cancer: a specific type of glycoform of haptoglobin,

and possibly other serum glycoproteins, with a different function after uptake into tissue

cells. PLoS ONE in press.

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Docent Ramin Massoumi

Lund University, Dept of Laboratory Medicine

Address: SUS Malmö, Entrance 78, 2nd floor, SE-205 02 Malmö, Sweden

Phone: +46-40-33 12 28

Email: ramin.massoumi@med.lu.se

Tumor entities of interest:

Skin cancer, Breast cancer, Liver cancer

Group members:

Rajeswara Pannem

Kristofer Ahlqvist

Gina Hallgren

Saamarthy Karunakar

Technologies of interest:

  1. Generating transgenic animals to define specific gene function.
  2. Studying the function of the specific gene during progression of cancer which is followed after tumor induction in a specific organ in the animal.
  3. Studying tissue samples from patients with cancer and correlating to the gene function and signaling pathway in animal.
  4. Treatment of animals and the human tissue platforms with different drugs as suggested treatment methods in human cancer patients.

Research abstract: The post-translational modification of different proteins via direct, covalent ubiquitin attachment is an important process for different cellular processes including survival and proliferation. The fate of the protein is decided by the type of poly-ubiquitination. For example, poly-ubiquitination through lysine48 (Lys48)-linkages targets the substrate for degradation by the proteosome machinery, while lysine63 (Lys63)-linked ubiquitin chains add new functional properties to the modified protein. The action of the E1, E2 and E3 ligation enzymes (E3) responsible for the attachment of the ubiquitin moieties to the substrate is reversed by the action of deubiquitination enzymes (DUB). The human genome encodes a large number of putative E3 ligases and DUBs and accumulating evidence indicates that most of these enzymes regulate a limited number of proteins and pathways. The specificity is defined by the recognition of the target protein and the attached ubiquitin polymer-chains or removal of the chains allowing a great degree of selectivity. The challenge of our research is to find the signaling pathways and novel substrates for specific E3 ligases and DUBs involved in cancer development.

The main objective of our research is to understand the function of ubiquitin ligation and deubiquitin enzymes as well as their substrates for diagnostic and therapeutic target of cancer.

Understanding the function of these genes in quiescent tissue, as well as pre-cancerous lesions and invasive cancers of distinct tissues/organs can help to improve the diagnosis and treatment of cancer patients.


Professor Sven Påhlman

Laboratory Medicine, Malmö, Lund University

Address: SUS Malmö, Center for Molecular Pathology, Entrance 78, SE-205 02, Malmö

Phone: +46-40-33 74 03

Email: sven.pahlman@med.lu.se

Tumor entities of interest: Neuroblastoma, Breast cancer, Lung cancer

Group members:

Helen Pettersson, Dr. med. vet.

Annika Jögi, Dr. med. vet.

Caroline Wigerup, Dr. med.vet.

Daniel Bexell, läkare, Dr med.vet.

Alexander Pietras, Dr. med. vet.

Karolina Helczynska, läkare, Dr. med. vet.

Siv Beckman, Fo. Ing.

Elisabet Johansson, Fo. Ing.

Kristin Lindell, sekreterare

Anna-Maria Larsson, läkare, Dr. med.vet.

Matilda Persson, FM doktorand

Sofie Johnsson, Tekn mag, doktorand

Marica Vaapil, FM doktorand

Susann Schiebel, BS, doktorand

Research subject: Characterization of the hypoxic phenotype in solid tumors with focus on HIF-2a and tumor initiating/stem cells in neuroblastoma and breast cancer.

Unraveling the hypoxic response in small cell lung carcinomas, which seem to lack HIF-2a expression.

Decipher the role of EPO receptors in non-erythroid tumors, their EPO independent activation in breast cancer, a the putative role of estrogen receptors in the activation mechanism.

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PhD Markus Ringnér

Lund University, Clinical Sciences, Lund

Address: BMC C13, 221 84 Lund, Sweden

Phone:

Email: markus.ringner@gmail.com

Tumor entities of interest:

Breast cancer

Group members:

Johan Staaf

Karolina Holm

Technologies of interest:

Research abstract:

Our research is centered on characterizing breast cancer by utilizing genome-wide measurements of expression levels, DNA copy numbers, methylation status, and sequences of genes, and to integrate these different layers of information using computational methods. Specific projects we are working on include:

- Comprehensive identification of transcriptional programs in breast cancer.

- Characterization of molecular subtypes of breast cancer at the epigenetic level.

- Investigations of HER2-positive breast cancer at various molecular levels.

- Development of analysis methods to be able to utilize new genomic technologies for measurements of heterogeneous tumor samples.


PhD Carlos Rovira

​Institute of Clinical Sciences, Dept. of Oncology, Canceromics Branch,Lund University

Address: BMC C13, 221 84 Lund, Sweden

Phone: +46-46-222 47 73

Email: carlos.rovira@med.lu.se

Tumor entities of interest:

Breast and collaborations in leukemia

Group members:

Helena Persson, Post-doc

Inga Newie, PhD student (BioCARE)

One vacant post-doc position for bioinformaticians

Technologies of interest:

  • Small RNA (siRNA, miRNA etc) technologies
  • Next-generation sequencing
  • Bioinformatics

Research abstract: The aims of our research are to contribute to a better understanding of the role of non-coding RNAs in cancer development. Taking advantage of existing cancer registers and large sample collections preserved in our large and well catalogued biobanks, we focus our efforts principally on the study of breast cancer. The motivation behind our research can be divided in two fields. First, to learn how non-coding RNAs regulate and promote carcinogenesis and secondly, to identify non-coding transcripts that can be used as biomarkers.

Our research is interdisciplinary. It combines experimental laboratory work with bioinformatics. To characterize the expression of non-coding RNAs in normal tissues, breast tumors and circulating body fluids we apply massive parallel sequencing techniques. This information is used to find known non-coding genes associated with the disease and to identify new human non-coding RNAs that could be of importance.

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Professor Lars Rönnstrand

Lund University, Dept of Laboratory Medicine, Malmö.

Address: ​Experimental Clinical Chemistry, Wallenberg Laboratory Entrance 46, 5th floor,

SUS-Malmö, 20502 Malmö

Phone: +46- 40-33 72 22

Email: Lars.Ronnstrand@med.lu.se

Tumor entities of interest:  

Gastrointestinal stromal tumors, breast cancer, acute myeloid leukemia, malignant melanoma.

Group members:

Jianmin Sun, postdoc;

Kazi Julhash Uddin, postdoc,

Shruti Agarwal, postdoc,

Tine Thingholm, postdoc, guest researcher, from 2011-01-01;

Elena Razumovskaya, graduate student;

Bengt Phung, graduate student;

Oscar Lindblad, graduate student,

Susanne Bengtsson, laboratory technician

Technologies of interest:

(I e methods we are using or are interested in using in the future) : immunoprecipitation and Western blotting, confocal microscopy, immunofluorescence, animal models, phosphoproteomics, Tandem affinity purification, phosphospecific antibodies made in-house, other antibodies made in-house, transformation assays (proliferation, survival assays, growth in semi-solid medium).

Research abstract:

Molecular dissection of signal transduction pathways through the stem cell factor receptor/c-kit and Flt3 in normal and pathological conditions

Purpose and aims

- To investigate the molecular mechanisms by which oncogenic mutants of the two receptor tyrosine kinases c-Kit and Flt3 transform different cell types and identify downstream signal transduction molecules that differ between wild-type and oncogenic receptors and elucidate their mechanism of action

- Identify phosphorylation sites in receptor tyrosine kinases and downstream signal transduction molecules for the use in mechanistic studies.

- Generate phosphospecific antibodies as such sites to be potentially used for diagnostic purposes.

- By use of animal models analyze the function of individual signaling molecules in Flt3 and c-Kit mediated transformation

- To investigate the role of alternative splice forms of these receptors in hematologic malignancies

- Investigate the mechanism of c-Kit signaling in melanoma and the role of the transcription factor MITF

- Studies on the mechanisms of negative regulation of Flt3.

Project web page: http://www.ronnstrandlab.com

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Assistant Professor Lao Saal

Lund University, Dept. of Oncology, Clinical Sciences Lund

Address: CREATE Health Centre, BMC C1322b, Lund University, SE-22184, Lund, Sweden

Phone: +46-46-2220365

Email: lao.saal@med.lu.se

Tumor entities of interest:

Breast cancer

Group members:

Eleonor Olsson

Lianne Hogendorf

Ingrid Caro-Östergren

Nabeela Ilias

Technologies of interest:

*Next-generation sequencing

* Genomics (microarray, aCGH, SNP/CNV)

* Bioinformatics

* In vitro models

* Real-time cell analysis

* Pharmacogenomics

* Immunohistochemistry

* Clinical cancer diagnostic assays

Research abstract:

My research as well as the work of others has highlighted the role of the PTEN/PI3K/AKT pathway as a key promotor of tumorigenesis and as a target for therapeutic modulation, in particular for breast cancer. With a particular interest in this pathway, my research applies recent advances in genome-wide technologies to study breast cancer biology with the goal of translating our findings into new clinical applications. Specifically, we aim to:

1. Discover the patterns of gene mutation, genomic aberrations, and gene expression changes within human breast tumors

2. Understand the relationship of these aberration patterns to clinicopathological parameters such as recurrence and patient survival

3. Study the functional significance of identified aberrations in model systems

4. Utilize this "-omic" information to design and test rational combinatorial therapeutics that target more specifically the actual cancer mutations and pathways that are active in a individual patient's tumor

5. Validate and translate to the clinic new biomarker diagnostic assays for selection of optimal therapy and monitoring response to therapy

6. Develop core bioresources and technology/bioinformatics infrastructure

Our research is facilitated by close cooperation with fellow research units of the Canceromics Branch and Division of Oncology, collaborations internationally, partnership with clinical oncologists, surgeons, and pathologists, and participation as one of the principal executors of the South Sweden Canceromics Analysis Network - Breast (SCAN-B) Initiative.

Translational Oncogenomics Unit webpage: http://www.med.lu.se/english/klinvetlund/canceromics/research/translational_oncogenomics

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Professor Göran Stenman

Sahlgrenska Cancer Center, Dept. of Pathology, Sahlgrenska Academy at University of Gothenburg

Address: Box 425, 405 30 Gothenburg, Sweden

Phone: +46 31 786 6733

Email: goran.stenman@llcr.med.gu.se

Tumor entities of interest: 

Head and neck cancer, reast cancer, skin tumors, soft tissue tumors.

Group members:

Mattias Andersson, PhD, postdoc

André Fehr, PhD, postdoc

Fredrik Persson, MD, PhD, postdoc

Kaarina Sundelin, MD, PhD

Ywonne Andrén, MSc

Marta Persson, PhD student

Sarah von Holstein, PhD student

Technologies of interest:

Genomics

Expression and CGH arrays

siRNA

drug screening

Research abstract:

The overall goals of this project are to (1) identify and molecularly characterize chromosome changes in salivary gland, breast, and skin tumors and to correlate the changes to the phenotype and biological behavior of the tumors; (2) study the pathogenetic and clinical significance of fusion oncogenes in these tumors; (3) identify novel fusion oncogenes and elucidate their molecular consequences; (4) study the TWIST1 and FGFR genes and their roles in the development of hereditary breast cancer.

Workplan: Chromosome changes are characterized using molecular genetic methods incl. array-based CGH. Genes localized at translocation breakpoints are identified by positional cloning, CGH- and expression-arrays. The functions, mechanisms of activation, and expression patterns of the genes are studied by molecular and cell biological methods. Tumor-specific mouse models will be used for studies of in vivo functions.

Significance: High-resolution molecular genetic methods provide new and unique opportunities to molecularly and clinically classify tumors and to identify novel cancer genes such as the MYB gene fusions we recently found. Functional studies of fusion oncogenes and hereditary cancer genes provide knowledge about novel pathogenetic mechanisms and signaling pathways of importance for the genesis and progression of sporadic and hereditary cancers and open up new avenues for development of targeted cancer therapies.

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BioCARE Lund University - Entrance 78, SUS Malmö - 205 02 Malmö - +46-40-331146

BioCARE University of Gothenburg - Cancer Center Sahlgrenska - Box 425 - 405 30 Göteborg - +46-31-7860000

Email BioCARE - www.biocare.nu

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