Jenny L Persson

Exist Metastatic disease represents a major clinical challenge. The long-term goal of our study is to gain deeper understanding of cellular mechanisms underlying cancer metastasis. We focus on identification and validation of new predictive biomarkers and drug targets that are specifically for metastatic cancer. We recently focus on studying the role of lipid kinases in particular, phosphatidylinositol 4-phosphate 5-kinase alpha that is responsible for activation PI3K/AKT pathways in cancer cell survival and metastasis. We are using prostate cancer and breast cancer clinical samples. This will allow stratification of subgroups suffering metastatic disease and poor response to treatment, which may be treated by targeted and personalized therapies. We will explore the role of the multiple mechanisms involving lipid kinases, vascular pathways and cell cycle signalling complexes to promote prostate cancer metastasis. We will further apply innovative targeted therapy using kinase inhibitors alone or in combination with anticancer drugs on in vivo metastatic cancer models.  We apply the methods such as single cell sequencing of the circulating tumor cells or freshly isolated primary and metastatic tumors. Genomic approaches are complemented with tissue microarrays (TMAs) technologies. Xenografts or transgenic mouse models of human prostate cancer are also applied for functional analyses.

In our on-going study, we developed mouse model to mimic distant metastasis and bone metastasis by injecting prostate cancer cells overexpressing the gene of interests into the tail vein of irradiated nude mice, our intriguing results showed that the majority of mice that received tumor cells overexpressing the key factors that are involved in hormone production had distant metastasis to the bone marrow, liver and lung in contrast to the control mice where no bone metastasis was detected. In the proposed study, we will apply this novel model to investigate the new molecular and cellular mechanisms that are associated with lipid kinases underlying cancer bone metastasis. Our study will provide new information to define the complexity of the molecular pathways in cancer metastasis and treatment response, and provide new strategies to improve personalized therapy.

  1. Miftakhova R, Hedblom A, Semenas J, Robinson B, Simoulis A, Malm J, Rizvanov A, Heery D, Mongan NP, Maitland NJ, Allegrucci C, Persson JL. Cyclin A1 and P450 aromatase promote homing and growth of stem-like prostate cancer cells to bone marrow. Cancer Research. 2016, Feb 26, [Epub ahead of print].
     
  2. Miftakhova R, Hedblom A, Batkiewicz L, Anagnosaki L, Zhang Y, Sjölander A, Wingren AG, Wolgemuth DJ, Persson JL. Cyclin A1 regulates the interactions between mouse haematopoietic stem and progenitor cells and their niches. Cell Cycle. 2015; 14(12):1948-60.
  3. Semenas J, Hedblom A, Miftakhova RR, Sarwar M, Larsson R, Shcherbina L, Johansson ME, Härkönen P, Sterner O, Persson JL. The role of PI3K/AKT-related PIP5K1α and the discovery of its selective inhibitor for treatment of advanced prostate cancer. Proc Natl Acad Sci U S A. 2014; 111:E3689-98.
     
  4. Hedblom A, Laursen KB, Miftakhova R, Sarwar M, Anagnostaki L, Bredberg A, Mongan NP, Gudas LJ,  Persson JL. The role of CDK1 and its functional link with RARγ in treatment response of acute myeloid leukemia and in ATRA-mediated effects on cell growth and differentiation. Cell Cycle 2013; 12:1251-1266.
     
  5. Wegiel B, Gallo D, Czismadia E, Harris C, Belcher J,  Penacho N, Seth, P, Sukhatme V,  Ahmed A, Helczynski L, Bjartell A, Persson JL, Otterbein LE. Carbon Monoxide Induces Mitochondrial Stress to Inhibit Tumor Growth. Cancer Research 2013; 73:7009-7021.

Publication list

We seek a PhD student at the Department of Molecular Biology. The PhD program is a joint program Under EU Innovative Training Network. The coordinator is Malmö University, Sweden. The partner Institutions include the research groups from Copenhagen, Germany, Finland.

The project aims to explore the utility of molecularly imprinted probes to target tumor specific molecules including glycans and lipid proteins and cell surface receptors. The study will further focus on identify and characterize the clinical meanings of biomarkers and molecular mechanisms of cancer cell growth and metastasis, and will further develop and validate the “plastic antibodies” to visualize cancer  cellular proteins and interactions between cancer and immune cells in real-time. Primary and metastatic cancer tissues from patients with prostate cancer and breast cancer, and blood cancer and various types of cancer cell lines will be used. Employment is limited to four years, starting after being selected through evaluation and interview process. Application deadline is 2017-04-20.

Project

Cancer is estimated as a main cause of death world-wide and over 1.3 million patients die of cancer in European Union annually (Malvezzi et al., 2015). In 2017, over 1.6 million new cancer cases and over 0.6 million cancer-related deaths are estimated to occur in the United States.  Despite improvement in cancer therapy, a large group of patients do not respond to the treatments. Alterations in glycosylation, lipid kinases, lipids, cell surface and hormone receptors contribute to tumor growth, angiogenesis and invasion.  It is an urgent need to develop novel biomarkers that can recognize cancer cells at early stage and during cancer progression as well.

The goal of this project is to develop of molecularly imprinted plastic antibodies that target tumor specific molecules including glycans and cell face receptors and lipids for visualization of cancer spreading in circulations and to distant tissues such as bone and brain. As study materials, primary tumor cells, cell lines and laboratory animal models will be used to study the meanings of cellular pathways and underlying mechanism for difficult-treated tumor. Flow cytometry cell sorting, single cell-based RNA-seq, analyze tissue microarrays, bioinformatics and statistical analysis, molecular biological assays, cell-culture model and in vivo models are included in the project.

Eligibility and qualifications

You must have a bachelor degree of 240 credits (ECTS), including 60 credits at advanced level. You should have including biochemistry, medicinal chemistry, cell and molecular biology, genetics, physiology, and independent work. You must have completed animal courses and have worked with cancer cell lines, cancer tissues from patients and in vivo models.

You must have good English skills and be proficient in both oral and written communication in English. You must be motivated and critical thinking and able to pursue projects independently and have good abilities to communicate and cooperation with colleagues at national and international levels.

You should be very interested to develop new technologies and models. Previous work experience in tumor biology and molecular biology and animal model is particularly meritorious.

You should not already possess a doctorate degree.

You should be  willing to move to a country within the network  in which you have not lived for more than 12 months over the last 3 years.

You should be proficient in both written and spoken English.

Application
You apply through our e-recruitment system MyNetwork before 2017-04-20.

The application shall consist of the following:

A CV, a cover letter including a brief description of your research interests and reasons for why you are applying and why you are suited to postgraduate place certified copies of diplomas, certificates and testimonials copies of theses and publications the name and contact information for two referees

Documents sent electronically should be in MS Word or PDF format.

A selection will be made among eligible applicants based on their qualifications and their ability to benefit from research training. After the selection process begins the process of admission to postgraduate level.

Basis of assessment

The evaluation of the candidate's ability and potential to perform well is based primarily on:

1. Knowledge and skills relevant to postgraduate studies in the field of research, 2. The ability to formulate and solve scientific questions. 3. Skills in written and oral communication in English. 4. Other experience relevant to postgraduate studies, such as professional experience. Good interpersonal skills, drive and independent work considered positive merit. A decision on admission will not be taken until an individual study plan has been approved by the department's graduate studies committee.

Other information
The appointment is aimed at a doctorate and is limited to four years full time. If part-time teaching (maximum 20%) can be offered extended employment.

To start immediately or by arrangement.

Salary is done according to the established wage ladder for doctoral position. According to the Higher Education Ordinance (Chapter 12, Section 2), the decision on the appointment is final.

More about us
Department of Molecular Biology, belonging to both the medical and technical Science has about 200 employees. The department's main tasks are research and postgraduate, graduate and undergraduate level. For more information, see www.molbiol.umu.se 

The Glycoimaging website can now be reached here:  glycoimaging.mah.se 

Publications

Author

Title

Year sorteringsordning

Fulltext

Metzler, Veronika M.
de Brot, Simone
Robinson, Robert S.; et al.

Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development
Placenta, 56: 79-85

2017

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Fulton, Joel
Mazumder, Bismoy
Whitchurch, Jonathan B.; et al.

Heterodimers of photoreceptor-specific nuclear receptor (PNR/NR2E3) and peroxisome proliferator-activated receptor-gamma (PPAR gamma) are disrupted by retinal disease-associated mutations
Cell Death and Disease, 8

2017

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Kunkl, Martina
Porciello, Nicla
Mastrogiovanni, Marta; et al.

ISA-2011B, a Phosphatidylinositol 4-Phosphate 5-Kinase alpha Inhibitor, impairs CD28-Dependent Costimulatory and Pro-inflammatory Signals in Human T Lymphocytes
Frontiers in Immunology, 8

2017

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Gomzikova, Marina O.
Zhuravleva, Margarita N.
Miftakhova, Regina R.; et al.

Cytochalasin B-induced membrane vesicles convey angiogenic activity of parental cells
OncoTarget, 8(41): 70496-70507

2017

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Shah, Mansi
Cardenas, Ryan
Wang, Belinda; et al.

HOXC8 regulates self-renewal, differentiation and transformation of breast cancer stem cells
Molecular Cancer, 16

2017

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Sarwar, Martuza
Semenas, Julius
Miftakhova, Regina; et al.

Targeted suppression of AR-V7 using PIP5K1 alpha inhibitor overcomes enzalutamide resistance in prostate cancer cells
OncoTarget, 7(39): 63065-63081

2016

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