Project List

SUBPROJECT # 1. ROLE OF BMP9 IN LIVER DISEASES.

ESR 1– Leiden University Medical Center (LUMC)

Title: Role of BMP9/endoglin/ALK1 signalling in CLD
Supervisors: P ten Dijke / M-J Goumans (LUMC)

Collaborators: S Dooley (UHEI), B Herrera (UCM), Galapagos.
Description: BMP9 is expressed in the liver. The co-receptor endoglin and the TGF-β family type I receptor ALK1 bind BMP9 with high affinity. BMP9-induced cellular responses can be selectively inhibited by an ALK1-Fc ligand trap. Expression of endoglin is induced during activation of HSC. Further, phosphorylated Smad1, an intracellular effector of BMP9, accumulates during liver fibrosis in an experimental mouse model. This ESR aims to investigate BMP9/endoglin/ALK1 signalling in liver fibrosis using cultured hepatocytes and HSC, as well as mouse models of chemically-induced liver fibrosis (CCl4, BDL) and genetic models (Mdr2-/-). Different animal models will be used: mice that are heterozygous for endoglin or ALK1, overexpressing BMP9, ALK1-Fc or endoglin-Fc ligand trap after adenoviral infection or after treatment with neutralizing antibodies targeting BMP9, endoglin or ALK1.
Deliverables: Role of BMP9, ALK1 and endoglin in liver fibrosis.

ESR 2 – Complutense University, Madrid (UMC)

Title: BMP-9 in CLD – in vitro and in vivo studies.
Supervisors: B Herrera / A Sánchez (UCM)
Collaborators: I Fabregat (IDIBELL), P ten Dijke (LUMC), S Dooley (UHEI).
Description: Bone morphogenetic proteins (BMP), originally identified for their ability to induce ectopic bone formation, heal bone defects and induce cartilage formation, belong to the TGF-βsuperfamily. BMPs have since been described as multifunctional regulators of development, cell proliferation, differentiation and apoptosis in many tissues and organs. Additionally, BMPs play an important role in adult tissue homeostasis and are implicated in a variety of pathophysiological processes including cancer. Despite the fact that BMP9 was first isolated from developing liver, little is known about the role of BMP9 in liver cells. Aim of this ESR is to study BMP9 in liver pathology, especially CLD. We will use BMP9 knock-out mice to obtain cell lines such as hepatocytes and oval cells (mouse PC) for in vitrostudies and we will challenge the mice with partial hepatectomy, CCl4 and DEN, agents that cause liver damage, to analyse the role ofBMP9 during liver regeneration, and during chemicallyinduced fibrosis and hepatocarcinogenesis, respectively,in vivo.
Deliverables: in vitroand in vivocharacterization of the role of BMP9 in different liver pathophysiological situations.


SUBPROJECT # 2. TGF-β AND LIVER STEM CELLS. RELEVANCE IN LIVER PATHOLOGIES

ESR 3– IDIBELL, Barcelona

Title: TGF- β and (human) liver stem cells in liver pathologies
Supervisors: I Fabregat, with E Navarro and A Fabra (IDIBELL)
Collaborators: A. Sánchez (UCM), A Moustakas (UU), W Mikulits (MUW), S Dooley (UHEI) and J. Dotor (DIGNA)
Description: TGF-β induces an epithelial-mesenchymal transition (EMT) process in hepatocytes and HCC cells, which may confer properties of liver stem cells. TGF- β dependent EMT in FaO rat hepatoma cells correlates withup-regulated chemokine receptor CXCR4 expression in the presumptive migration front, indicating a role in cell migration and acquisition of stem cell properties. In this ESR, we will (1) analyse the relevance of autocrine TGF-β effects and its abrogation on aquisition of a dedifferentiated phenotype and properties of cancer stem cells; (2) isolate HCC cell lines that stably maintain the EMT phenotype after TGF-β treatment and analyze their fibrogenic and tumorigenic capacity in vivo, when transplanted into immunosuppressed mice; (3) Analyse crosstalk between TGF-β and the CXCR4/SDF-1 axis in human HCC cells and its relevance for acquisition of a de-differentiated phenotype with respect to cell polarization, survival and migration.
Deliverables: TGF-β role in conferring a liver stem cell phenotype and its crosstalk with the CXCR4/SDF-1 axis in human HCC.


SUBPROJECT # 3. TARGETING TGF-β SIGNALLING IN CHRONIC LIVER DISEASE AND HCC

ESR 4 – Univ. of Heidelberg (UH)

Title: Targeting TGF-β signalling in CLD and HCC using compounds derived from fungi
Supervisor: S Dooley (UHEI), with S Wölfl and G Erkel (Univ. of Kaiserslautern)
Collaborators: A Moustakas (UU).
Description: With a combination of systems biology, chemical biology and expertise in CLD pathology, we aim at new therapeutic concepts not obvious in classical drug development. The pharmacological potential of recently isolated natural compounds with inhibitory effects on disease related IL-6 and TGF-β signalling pathways (e.g., galiellalactone and dehydrocurvularin), will serve as lead structures to model the regulatory network of CLD and treatment response. With this systems biology approach, we will be able to generate an IL6/TGF-β dependent disease signature from challenged liver cells, thus defining the significance of specific targets addressed by the lead compounds. Chemical variation will be used to definepharmacophors, improve pharmacological potency, and use these to further elucidate relevance of regulatory events with disease-related functional assays. In a toxicogenomic approach, global gene transcription profiling will predict toxic responses, before selected compounds will be preclinically evaluated in different liver disease models in vivo.
Deliverables: Comprehensive model of the regulatory interaction network of CLD. Identification of regulatory nodes promising for drug intervention and new lead compounds, their structural analysis and chemical synthesis.

ESR 5– Univ. of Heidelberg (UH)

Title: Targeting TGF-β signalling in CLD and HCC using anti-sense oligonucleotides
Supervisor: S Dooley (UHEI), Anti-Sense Pharma
Collaborators: P ten Dijke / H van Dam (LUMC)
Description: TGF- β is highly expressed in many different fibrotictissues, including liver. In this ESR, we will selectively target TGF-β1 and TGF-β2 expression in different models of CLD and HCC (CCl4, BDL, Mdr2-/-) using anti-sense oligonucleotides. Inaddition, we will target the TGF-β type I receptor ALK5 using antisense oligonucleotides that induce exon skipping and inactivate ALK5. TGF-β or TGF-β receptor expression inhibition with such an approach was already shown in vivousing other animal models. Isarna Therapeutics will participate facilitating reagents and evaluating the anti-Sense against TGF-β.
Deliverables: Evidence for liver fibrosis inhibition with anti-sense nucleotides targeting key TGF-β signalling pathway components.

ESR 6 – Univ. of Bari Medical School (UB)

Title: Regulating the tumor-host interaction at the immunological and biological level by targeting TGF-β with specific inhibitors
Supervisor: G Giannelli / A Mazzocca (UB).
Collaborators: W Mikulits (MUW), S Dooley (UHEI), I Fabregat (IDIBELL).
Description: Fibroblasts present around tumours play a key role in promoting the invasive tumour phenotype. TGF- β is a key molecule in regulating progression of CLD and HCC. By inhibiting the TGF- β pathway with a selective receptor I kinase inhibitor, spreading of HCC cells into surrounding tissue, intravasation, angiogenesis and stroma/tumour communication can be blunted, providing a new therapeutic paradigm in that blocking just one molecular target leads to multifunctional effects. We hypothesize that TGF- β is responsible for alterations of the crosstalk between fibroblasts and HCC cells and subsequentclinical outcomes. This ESR comprises cellular and biochemical characterization of freshly isolated primary cultures of tumour fibroblasts (also named cancerassociated fibroblasts) or from peritumoural tissue (named peritumoural fibroblasts) focusing on activation of the TGF-β pathway, and adopting chip array as a larger molecular scale screening tool. Further, the impact of selective inhibition of the TGF- β pathway, focusing on fibroblast and immune system components, will be assessed by investigating effects on HCC progression, in vitroand in vivo, and by correlating experimental data with clinical outcomes.
Deliverables: Role of the TGF- β pathway in modulating the invasive phenotype of HCC and correlations with clinical outcome.


SUBPROJECT # 4. NOVEL INHIBITORS AGAINST TGF-β-INDUCED EMT AND THEIR IMPACT ON HCC

ESR 7– Medical University of Vienna (MUW)

Title: Targeting the TGF-β tumour-promoting function in hepatocellular EMT and HCC progression
Supervisor: W Mikulits (MUW)
Collaborators: A Moustakas (UU), G Giannelli (UB), I Fabregat (IDIBELL), J Dotor (DIGNA Biotech)
Description: We have developed mouse and human models of hepatocellular EMT, which correlate with important aspects of HCC progression such as cancer cell invasion and intrahepatic metastasis. These 3D hepatosphere EMT models show insensitivity against anti-proliferative TGF-β effects and tumour-promoting, autocrine TGF-βregulation, and are highly suitable to investigate the efficacy and specificity of anti-cancer compounds in preclinical studies. In this ESR, we aim at exploiting 3D cellular EMT models for the assessment of novel anti- TGF-β drugs. We will concentrate on inhibition of tumour cell migration and invasion as well as on apoptosis induction in absence and presence of tumour-associated stroma (myofibroblasts, MFB and/or Kupffer cells, KC). Labelled heterotypic 3D cultures will particularly allow studying phenotypic changes of HCC cells upon paracrine TGF- βregulation provided by the tumour-stroma. Efficacy of anti-TGF-β drugs will be further investigated by their ability to block trans-endothelial migration of HCC cells, a key event in intrahepatic metastasis. Blood vessel invasion will be mimicked by co-cultivation of HCC cells with tumour-derived endothelial cells. Overall, we will assess the effects of delivered soluble inhibitors on HCC invasiveness and intravasation.
Deliverables: Efficacy of pharmacological intervention with TGF- β signalling during EMT to blunt HCC cell invasion and entry into the circulatory system.

ESR 8– Uppsala University (UU)

Title: Novel inhibitors against EMT and their impact on hepatic carcinoma survival and differentiation
Supervisor: A Moustakas (UU)
Collaborators: S Dooley (UHEI), P ten Dijke (LUMC), W Mikulits (MUW), I Fabregat (IDIBELL)
Description: We have performed a large-scale screen for chemical compounds that inhibit EMT in a human keratinocyte model. The selected set of inhibitors needs to be tested in human tumour cells and mouse fibrosis/cancer models. In this ESR, we will test a panel of these compounds and the response of few HCC cell models. Features of HCC proliferation, survival, adhesion,migration and invasion in 3D matrix systems will be analyzed using titrations of the compounds. Marker analysis for specific EMT regulators and for liver-specific differentiation factors will be performed and the impact of the compounds will be evaluated. The most successful small set of compounds will be tested in an in vivomodel of liver fibrosis and associated HCC (Mdr2-/-).
Deliverables: Compound short-list for further pre-clinical development.


SUBPROJECT # 5. NOVEL STRATEGIES FOR THE DELIVERY OF TGF-β SIGNALLING INHIBITORS INTO HCC CELLS. LARGE SCALE ANALYSIS OF BIOMARKERS FOR ANALYSIS OF DRUG EFFECTIVENESS.

ESR 9– CNR Nano

Title: Development and production of magneto-fluorescent decorated and TGFβ-inhibitors-loaded microcapsules for delivery into HCC cells.
Supervisor: S. Leporatti / V. Vergaro (CNR-Nano).
Collaborators: G. Giannelli (UB)
Description: Multifunctional capsules with tuneable permeability will be fabricated starting from materials that are entirely biocompatible and biodegradable. In addition to shielding the contents (drugs) from chemical and biological degradation, capsules will be designed with functionalities to: a) monitor their in vitro and in vivo distribution; b) target specific hepatocellular carcinoma (HCC) cell types. Optimal biocompatible and biodegradable polyelectrolyte pairs (eg dextran and polyarginine) will be selected and the best conditions (pH, temperature, ionic strength) for multilayer growth onto colloidal particles (mainly CaCO3) will be determined. Multilayer coating will be monitored by zeta potential measurements, in order to determine the charge variation caused by the alternation of oppositely charged polyelectrolyte layers. Fluorophores (eg rhodamine and fluorescein) will be inserted in the coating, in order to allow microcapsule tracing in vitro. Confocal laser fluorescence scanning microscopy will be used to confirm the incorporation of fluorescent layers inside the capsule wall. Protocols for including magnetic materials (mainly superparamagnetic nanoparticles) in the capsule wall will be developed. The combination of magnetic and fluorescent functionalities is of primary importance because such properties will be largely relied on by other partners to monitor carriers distribution by in vivo real-time imaging. TGF- β-inhibitors loading strategies will be developed. Microcapsule permeability changes induced by temperature, ionic strength, pH or EM radiation will be explored. Alternatively, a complex between calcium carbonate cores and drug will be prepared before polyelectrolyte stratification. Drug-loaded microcapsules willbe characterised by scanning force and electron microscopy to verify encapsulation, and drug-entrapment will be quantified by spectroscopic techniques.
Deliverables:TGF-β-inhibitors loaded biocompatible capsules and their uptake characterisation.

ESR 10– Univ. of Bari Medical School (UB) & GenXPro

Title: Large scale analysis of biomarkers for drug effectiveness of TGF- β inhibitors.
Supervisor: G Giannelli / F Dituri (UB)
Collaborators: GenXPro.
Description: In vitro pharmacokinetic studies on a TGF-β inhibitor using large-scale analyses of downstream pathways driving, e.g., migratory activity of HCC cells, are particularly important for determining ideal treatment modalities. On the other hand, availability of biomarkers in blood samples to assess drug effectiveness is a key step in the development of clinical trials for new drugs. Thus, the present ESR will (1) analyse in vitroa wide range of potential downstream targets of the TGF-β pathway ; (2) inhibit HCC tumour progression in xenografts in vivo; (3)test a selection of these protein targets (i.e. kinases, E-cadherin, migratory proteins, etc) in blood samples and (4) correlate a panel of these biomarkers with clinical outcome of HCC tumour progression. GenXPro will collaborate with UB by contributing next-generation-sequencing based investigation of the nucleic acid content of treated and non treated xenografts and blood. Thus, high-resolution profiles will be established from mRNAs, small/microRNAs and genome-wide cytosine methylation from xenogrphas and blood to identify a set of easily scorable biomarkers and correlate a panel of these biomarkers with clinical outcome of HCC tumor progression. To identify biomarkers for a simple test to assess the efficacy of TGF-βRI inhibitor in vivo,large-scale data analysis including integration of transcriptomics (mRNA and smallRNAs) and epigenomics data is necessary and potential diagnostic biomarkers need to be validated individually by wet work.
Deliverables: Identify a simple test to assess drug efficacy (TGF-βRI inhibitor) in vivo.


SUBPROJECT # 3. TARGETING TGF-β SIGNALLING IN CHRONIC LIVER DISEASE AND HCC

ER1 – Galapagos BV

Title: Identification of genes that contribute to the development of liver fibrosis.
Supervisor: RAJ Janssen (Galapagos)
Collaborators: P. ten Dijke (LUMC)
Description: The goal of the ER project will be to identify genes thatcontribute to the development of liver fibrosis. This information would be used to design drugs against the proteins encoded by these genes. In the proposed project the trainee will set up novel cellular assays mimicking fibrosis related processes using human primary hepatocytes, macrophages, myofibroblasts, or other cell types. The cells will be triggered with the fibrosis related factors (e.g. TGFβ), and the production of fibrotic factors and mediators will be measured (e.g. ECM factors and metalloproteases). The assay should be amenable for high throughput screening purposes, with cell cultures in 96- or 384-well plates. Once a robust and reproducible high throughput assay has been developed with a significant window of the readout, the assay will be further validatedby knocking down individual genes that are known to play a role in the particular fibrotic process. The validated assays will be screened with an adenoviral library of over 11,000 different shRNA constructs that target over 4500 different genes encoding drugable proteins. Hits from these screens will be further validated in fibrosis related assays. In this project the trainee will learn how to set up robust cellular high throughput assays using human primary cells. She/he will learn how to screen such assays using state-of-the-art equipment and technologies and how to collect and analyze large data collections. The trainee will learn how to work in a team, according to ISO quality standards in an industrial setting using a project-based approach with tight deadlines and challenging goals. The trainee will learn how to record all results in such a way that the data can be used not only for publications but for IP applications as well. He/she will need to present the data regularly within the project team and within the company.


SUBPROJECT # 5. NOVEL STRATEGIES FOR THE DELIVERY OF TGF-β SIGNALLING INHIBITORS INTO HCC CELLS. LARGE SCALE ANALYSIS OF BIOMARKERS FOR ANALYSIS OF DRUG EFFECTIVENESS.

ER2 - GenXPro GmbH

Title: Bioinformatic analysis methods for identification of biomarkers to assess the efficacy of TGF-βRI inhibitors in vivo
Supervisor: Peter Winter (GenXPro)
Collaborators: G. Giannelli (UB) and S. Leporatti (CNR-Nano)
Description: Connected with their participation in the training of ESR 10, GenXPro will also incorporate one ER, which will test a set of available bioinformatic analysis methods, such as Gene Ontology mapping, pathway mapping (KEGG, BioCarta, Reactome) and respective enrichment (GSEA, iGA) and network analyses (mapping transcripts on PPI networks and identifying hubs) for their suitability to identify biomarkersfor a simple test to assess the efficacy of TGF-βRI inhibitor in vivo, based on data generated within the project and on other cancer data sets available at GenXPro. The results of such analyses need to be checked for their biologicaland medical plausibility by hand in order to identify the best suited and most reliable method. This requires an experienced researcher (at least 3 years of experience) who is familiar with the literature and ableto balance pros and cons of the different methods based on his/her independent judgment. Due to the large number of bioinformatical and statistical tests to be performed a minimum of 2 years is required.


SUBPROJECT # 6. INHIBITION OF TGF-β TO INCREASE ANTI HCV IMMUNITY

ER3 – DIGNA/CIMA

Title: Inhibition of TGF-βto increase anti HCV immunity
Supervisor: J. Dotor (DIGNA)
Collaborators: P. Sarobe / E. Feijoo (DIGNA/CIMA); I. Fabregat (IDIBELL).
Description:TGF-β is a pleiotropic cytokine with immunosuppressive effects on many cell populations. Increased levels of TGF-β have been described in chronic hepatitis C virus (HCV) infection, which is characterized by the lack of cellular antiviral immunity. Moreover, immunosuppressive cell populations, such as regulatory T cells, whose activation is dependent on TGF-β, are present at higher levels in patients chronically infected by HCV. Several viral proteins as well as cell populations activated by inflammatory conditions present during viral infection have been shown to induce TGF-β directly and indirectly. All these data suggest that inhibition of TGF-βin chronic HCV infection may provide a therapeutical benefit to these patients. The purpose of this project is to analyze the effect of TGF-β blockade on different in vitro models where HCV components have been shown to inhibit the functional properties of antiviral effector cells or to activate immunosuppressive cell populations. To this aim, we will culture immune cells in the presence of HCV components (proteins, HCV infected cells, etc) with or without TGF-β inhibitor peptides. Antiviral cell immunity, their expansion and functional properties, as well as the impact on immunosuppressive mechanisms will be studied in this context. Deliverable is to analyze the efficacy of TGF-β blockade on antiHCV immunity

Sisi Cai, MSc

Sisi Cai , MScSisi Cai was born in 1988 in China.

She completed her Bachelor’s Degree in Biological Sciencein June, 2010after 4 years’ study in 211 Base Class (a class officially set up by the Ministry of Education of China and with purpose of providing comprehensive training in bioscience and biotech) at the College of Life Sciences, Hunan Normal University, China.

In September, 2010 she started furthering her study for the degree of Msc. in Chemical Biology in the School of Pharmaceutical Sciences, Xiamen University, China. There she has put her main interest in researching the interaction of the orphan nuclear receptor Nur77 and the HBx (hepatitis B virus X protein). She received her Master Degree in June, 2013.

From August, 2013 Sisi Cai started working in Leiden University Medical Center, Netherland as Ph.D student under the supervision of Professor Peter ten Dijke and meanwhile as ESR in the network of IT-LIVER. Her work is centered on TGFβ-associated liver fibrosis and the later-on liver diseases.

2006.09-2010.06     B.Sc, Biological Science, College of Life Sciences, Hunan Normal University, Changsha, China

2010.09-2013.06   M.sc, Chemical Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, China

2013.06-Now     Ph.D, TGFbeta signal transduction, Leiden University Medical Center, Netherland

PUBLICATIONS:

  1. Gao, W., Liu, J., Hu, M., Huang, M., Cai, S., Zeng, Z., ... & Zhang, X. K. (2013). Regulation of Proteolytic Cleavage of Retinoid X Receptor-alpha by GSK-3β. Carcinogenesis.

 

 

Annalisa Addante

adante

was born in 1987 in Italy. She completed her Bachelor’s Degree in Healthcare and Pharmaceutical Biotechnology in 2009 at the Faculty of Biotechnology, University of Bari, Bari, Italy. Her bachelor thesis, under the supervision of Dr. Maria Elena Dell’Aquila, concerned the effects of phthalates on parameters of vitality and functionality of the cumulus-oocyte complex on equine. Then she did her Master Degree in Medical Biotechnology at the University of Rome “La Sapienza”. She completed her Master studies in 2011 with an internship concerning “Antagonism of the Angiotensin II receptor Type I and vascular remodelling: role of activation of Ang (1-7) / receptor Mas” in theClinical and Molecular Medicine Department. After this, she worked for six months at the EHS Platform of the Center for Biomolecular Nanotechnology, Italian Institute of Technology (IIT), Arnesano, Lecce, Italy. She is currently working as PhD student in the group of Dr. Aránzazu Sánchez Muñoz at the Department of Biochemistry and Molecular Biology, Universidad Complutense de Madrid (UCM), Madrid, Spain.

 
2009   B.Sc, Healthcare and Pharmaceutical Biotechnology, Faculty of Biotechnology, University of Bari

2011   M.Sc, Medical Biotechnology, University of Rome “La Sapienza”

2012   Collaborator, Center for Biomolecular Nanotechnology, Italian Institute of Technology (IIT)

2013   PhD student, Department of Biochemistry and Molecular Biology, Universidad Complutense de Madrid (UCM), Madrid, Spain

Andrea Malfettone, MSc

Andrea Malfettone, MScAndrea Malfettone was born in Italy, completed his Bachelor’s Degree in Biological Sciences in 2004 and his Master Degree in Biomedical Sciencesin 2007 at the Faculty of Mathematics, Physics and Natural Sciences, University of Bari, Bari, Italy. In 2004 he did his Bachelor Degree internship concerning “Effect of Cariporide on the activation kinetics of the membranous exchanger Na+/H+ in MDA-MB-435 breast cancer cells” under the supervision of Prof. Stephan J. Reshkin at the Department of Bioscience, Biotechnology and Pharmacological Sciences, University of Bari. In 2007 he pursued his Master thesis project focused on “NHERF1 through interaction with EGFR alters its localization and function in breast cancer” at the Department of Bioscience, Biotechnology and Pharmacological Sciences, University of Bari, under the supervision of Prof. Stephan J. Reshkin, in collaboration with the Clinical Experimental Oncology Laboratory, National Cancer Research Centre, Istituto Tumori “Giovanni Paolo II”, Bari, under the supervision of Dr. Angelo Paradiso. In 2011 he attended the Postgraduate Specialization School (5 years course) in Clinical Biochemistry developing the thesis project “Expression analysis of NHERF1 in breast cancer: biological and clinical aspects” at the School of Medicine, Department of Medical Biochemistry, Biology and Physics, University of Bari. He is currently working as PhD student in the group of Dr. Isabel Fabregat, at the Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.

Publications

  1. Bellizzi A, Mangia A, Chiriatti A, Petroni S, Quaranta M, Schittulli F, Malfettone A, Cardone RA, Paradiso A, Reshkin SJ. RhoA protein expression in primary breast cancers and matched lymphocytes is associated with progression of the disease. Int J Mol Med. 2008 Jul;22(1):25-31.
  2. Mangia A, Chiriatti A, Bellizzi A, Malfettone A, Stea B, Zito FA, Reshkin SJ, Simone G, Paradiso A. Biological role of NHERF1 protein expression in breast cancer. Histopathology. 2009 Nov;55(5):600-8.
  3. Mangia A, Tommasi S, Bruno M, Malfettone A, D'Amico C, Zito FA, Paradiso A, Simone G. Histological features of extratumoral breast lesions as a predictive factor of familial breast cancer. Oncol Rep. 2010 Jun;23(6):1641-5.
  4. Simone G, Mangia A, Malfettone A, Rubini V, Siciliano M, Di Benedetto A, Terrenato I, Novelli F, Mottolese M. Chromogenic in situ hybridization to detect EGFR gene copy number in cell blocks from fine-needle aspirates of non small cell lung carcinomas and lung metastases from colo-rectal cancer. J Exp Clin Cancer Res. 2010 Sep 15;29:125.
  5. Bellizzi A, Malfettone A, Cardone RA, Mangia A. NHERF1/EBP50 in Breast Cancer: Clinical Perspectives. Breast Care (Basel). 2010;5(2):86-90.
  6. Mangia A, Malfettone A, Simone G, Darvishian F. Old and new concepts in histopathological characterization of familial breast cancer. Ann Oncol. 2011 Jan;22 Suppl 1:i24-30. Review.
  7. Mangia A, Malfettone A, Saponaro C, Tommasi S, Simone G, Paradiso A. Human epidermal growth factor receptor 2, Na+/H+ exchanger regulatory factor 1, and breast cancer susceptibility gene-1 as new biomarkers for familial breast cancers. Hum Pathol. 2011 Nov;42(11):1589-95. doi: 10.1016/j.humpath.2011.01.010.
  8. Bellizzi A, Mangia A, Malfettone A, Cardone RA, Simone G, Reshkin SJ, Paradiso A. Na+/H+ exchanger regulatory factor 1 expression levels in blood and tissue predict breast tumour clinical behaviour. Histopathology. 2011 Jun;58(7):1086-95.
  9. Mangia A, Malfettone A, Rossi R, Paradiso A, Ranieri G, Simone G, Resta L. Tissue remodelling in breast cancer: human mast cell tryptase as an initiator of myofibroblast differentiation. Histopathology. 2011 Jun;58(7):1096-106.
  10. Malfettone A, Saponaro C, Paradiso A, Simone G, Mangia A. Peritumoral vascular invasion and NHERF1 expression define an immunophenotype of grade 2 invasive breast cancer associated with poor prognosis. BMC Cancer. 2012 Mar 22;12:106.
  11. Malfettone A, Silvestris N, Paradiso A, Mattioli E, Simone G, Mangia A. Overexpression of nuclear NHERF1 in advanced colorectal cancer: association with hypoxic microenvironment and tumor invasive phenotype. Exp Mol Pathol. 2012 Jun;92(3):296-303.
  12. Mangia A, Saponaro C, Malfettone A, Bisceglie D, Bellizzi A, Asselti M, Popescu O, Reshkin SJ, Paradiso A, Simone G. Involvement of nuclear NHERF1 in colorectal cancer progression. Oncol Rep. 2012 Sep;28(3):889-94.
  13. Saponaro C, Malfettone A, Ranieri G, Danza K, Simone G, Paradiso A, Mangia A. VEGF, HIF-1α Expression and MVD as an Angiogenic Network in Familial Breast Cancer. PLoS One. 2013;8(1):e53070.

 

Teng Feng, MSc

Teng Feng, MSc Teng Feng was born in 1984 in China. He got his bachelor’s degree of biotechnology  at  2007  and  his  master’s  degree  of  pharmacology  at 2010.

In 2007 he started  his master project “Screening and pharmacological evaluation  of  tumor  vascular  disrupting  agent  (VDA) derives  from Combretastatin  A-4”  at  school  of  medicine  and  pharmacy,  Ocean university  of  China.  In  2008  he  participated  in  the project  “Polymeric immunoglobulin  receptor  in  inflammation-induced  tum or  metastasis of human hepatocellular carcinoma” as an exchange student at Shanghai institute of Materia Medica, Chinese Academy of Sciences.

In 2010 he started his career as an associate scientist at department of oncology, Roche R&D Center (China). His research focus was assessment of new therapeutic targets in liver cancer.

He is currently working as a PhD student at the group of Prof. Steven Dooley at medical faculty Mannheim, Heidelberg University, Germany.

2010.7-2012.5   Associate Scientist, Department of Oncology, Roche R&D Center (China)
2007.9-2010.7   M.S. in Cancer Pharmacology, Ocean University of China
2008.9-2010.7   Exchange student, Shanghai Instituteof Materia Medica, Chinese Academy of Sciences
2003.9-2007.7   B.S. in Biotechnology, Dalian Ocean University

Publications

  1. Li Q, Gu X, Weng H, Ghafoory S, Liu Y, Feng T, et al. Bone morphogenetic protein-9 (BMP-9) induces  epithelial  to  mesenchymal  transition  (EMT)  in  hepatocellular  carcinoma  cells. Cancer Sci.2013 Jan 3. doi: 10.1111/cas.12093.(2011 IF: 3.3)
  2. Zhi-ting  Deng*,  Teng  Feng*,  Peng  Wang,  Xin  Qi  et  al.  Effects  of  the  Novel  Vascular Targeting  Agent  MDS-11P  On  Tumor  Vascularity  and  its  Antitumor  Activity.  Biochemical Pharmacology, 2011, 82(12):1832-42 (2011 IF: 4.7) (*Co-first Author)
  3. Jing Ai, Qing-juan Tang, Yan-lin Wu, Yang Xu, Teng Feng, Rui-yu Zhou, Yi Chen et al. The Role of Polymeric Immunoglobulin Receptor in Inflammation-induced Tumor Metastasis of Human  Hepatocellular  Carcinoma.  Journal  of  the  National  Cancer  Institute,  2011, 103(22):1-17. (2011 IF: 13.7)
  4. 4.  Feng Teng, Geng Mei-Yu, Li Jing. Research progress in small molecule vascular disrupting agents. Chinese Journal of New Drugs, 2010,19(24):2285-2289.(in Chinese)
  5. Lin Du, Teng Feng, Boyu Zhao et al. Alkaloids from a deep ocean sediment-derived fungus Penicillium sp. and their antitumor activities. The Journal of Antibiotics, 2010,63(4):165-70. (2011 IF: 1.6)
  6. Chuan  Rui  Zhang,  Hong  Bing  Liu,  Teng  Feng et  al.  Alkaloids  from  the  Leaves  of Daphniphyllum sub erticillatum.  Journal of Natural Products,  2009,72(9):1669-72. (2011 IF: 3.1)
  7. Xiu  li  Wang,  Teng  Feng,  Lei  Yang  et  al.  dbEST-derived  SSR  markers  in  sea  urchin (Hemicentrotus pulcherrimus). Conservation Genetics, 2008, 10 (3):729-731. (2011 IF:1.6)
  8. Feng  Teng,  Wang  Xiu  Li,  Chang  Ya  Qing.  Research  progress  and applications  of  PCR technology  on  disease  diagnose  in  aquaculture  animal.  Biotechnology  Bulletin, 2006,10(26):62-66.(in Chinese)

 

Tatiana Dediulia

was born in 1986 in Lithuania. She completed her Bachelor´s degree in Bhavna Rani, MSc
Biotechnology in 2009 and her Master´s degree in Molecular Biotechnology in 2010.
Although she is Lithuanian, she has resided in Spain since 1994 therefore she received her primary education in Spain.  She is currently working as Marie Curie Early Stage Researcher (PhD student) in the group of Prof. Steven Dooley at Department of Medicine II, Section Molecular Hepatology, Madical Faculty Mannheim, Heidelberg University, Germany.

In 2007 she participated and collaborated in some Parkinson projects in the Department of Molecular Medicine of University of Salamanca (Salamanca, Spain). One of these projects was awarded with the prize to the best communication at “I National Congress of Investigation for pre-PhD students in Health Science and II Complutense Conferences” of Universidad Complutense de Madrid (University, Madrid, Spain). 

In 2008 she made practices at “Translational and Experimental Oncology group: stem cells, cancer stem cells and cancer”laboratory in the Cancer Research Institute (CIC, Salamanca, Spain).

In 2010 she carried out a final project for her Master degree, “Study of expression and intracellular trafficking of CXCR4 receptor in hepatic carcinoma cells (Hep3B and PLC)” at “Molecular Oncology Laboratory (LOM)” in the Bellvitge Biomedical Research Institute (IDIBELL, Barcelona, Spain), and was recruited at Sant Pau Biomedical Research Institute (Barcelona, Spain) to work in a project called “Study of bad prognosis markers in Head and Neck Squamous Cell Carcinoma (HNSCC) and search for therapeutic alternatives” in the Molecular and Cellular Biology of Cancer group. At that time she also collaborated in a project with Clinical Hematology group.

Educational status

1.         2009-2010: M.Sc. Molecular Biotechnology, Faculty of Pharmacy, University of Barcelona (Spain)

2.         2004-2009: B.Sc. Biotechnology, Faculty of Biology, University of Salamanca (Spain)

Bhavna Rani, MSc

Bhavna Rani, MSc Bhavna Rani is currently working as Marie Curie Early Stage Researcher (PhD student) in the group of Prof. Gianluigi Giannelli at theDepartment of Emergency and Organ Transplantation, Section of Internal Medicine, Allergology and Clinical Immunology, University of Bari, Italy. She is an Indian and has received her primary education from India. Later on, she was awarded full scholarship from Dutch ministry of science, education and culture to pursue a specialized Masters in Oncology program at Vrije University (VU) Amsterdam, The Netherlands. She has performed wide array of research projects in the field of molecular and immuno-biology of brain tumors and liver regeneration at different levels in different European countries including the Netherlands, Sweden and Germany. She has been awarded with many International and National Scholarships during her masters studies. She has publications and contributions in peer reviewed journals like Hepatology (2012),Proceedings of National Conference on Genomics, Proteomics & Systems Biology, Indian Institute of Science (IISC), Bangalore, India (2008) andAsPac J. Mol.Biol. Biotechnol (2009). Her research interests include Cancer Immunology, Regenerative medicine and Translational research.

 

Educational status

  1. 2009-2011: Masters of Science (M.Sc.) Oncology VU / VUMC, Amsterdam, the Netherlands.
  2. 2006-2008: M.Sc. Biotechnology, Guru Jambeshwar University of Science and Technology, Hisar, India.
  3. 2003- 2006: B.Sc. Biotechnology, Kurukshetra University, India. 


Awards/Scholarships

  1. December, 2010- 1st June, 2011- Fellowship grant from Oncology Research Lab to undertake Master Thesis Project, Umeå University, Sweden.
  2. December, 2010- 1st June, 2011- Awarded Erasmus Placement Scholarship for six Months to support Master thesis project at Oncology Lab, Umeå University, Sweden.
  3. 2009 - Awarded prestigious “Huygens Scholarship (HSP)” for two years by Dutch Ministry for Education, Science & Culture (Nuffic), The Netherlands.
  4. 2006–2008- Awarded prestigious Department of Biotechnology (DBT), Govt. of India, scholarship for pursuing MSc Biotechnology at GJU, Hisar, India.

 

 

Petra Koudelkova , MSc

Petra Koudelkova , MScPetra Koudelkova was born in  1987 in  Czech Republic. She  achieved her  Bachelor  degree  in 2009  and  subsequent  Master  degree  in  2012 from  Biochemistry  at  the  Faculty  of  Science,  Palacky  University Olomouc, Czech Republic.

In  2008  she  started  her  bachelor  project  “The  Effect  of  N(6)-substituated  adenosine  derivatives  on  proliferation  and  cell  death  in tumour cells” at the Department of Biology, Faculty of Medicine, Palacky University Olomouc which led to obtaining B.Sc. in 2009 (Supervisor Doc. Petr Mlejnek CSc.).

In 2009-2010 she participated on the project  “The Effect of  Dithiocarbamate Complexes in Tumour  Liver  Cell  Lines”  (leader  Mgr.  Boris  Cvek,  Ph.D.)  at  the  Department  of  Molecular Biology and Genetics, Faculty of Science, Palacky University Olomouc.

In  2010-2011  she  gained  an  internship  at  the  world´s  leading  biotechnological  company Amgen (Division Amgen Research GmbH, Regensburg, Germany)  where she started on the beginning  as  an  intern  and  later  as  M.Sc.  student  with  master  project:  “Generation  and characterization  of  stable  expressing  cell  lines  using  different  approaches  for  targeted integration  into  genome  of  mammalian  cells”  (Supervisor  Markus  Hierl,  Dipl.-Ing.,  Cosupervisor Ralf Schwandner, Ph.D.) which led to obtaining M.Sc. in 2012.

Currently, she is working  as Ph.D. student in the group of  Prof. Wolfgang Mikulits  at Institute of Cancer Research, Medical University Vienna, Austria.

2009 – B.Sc. in Biochemistry, Palacky University in Olomouc, Czech Republic
2012 – M.Sc. in Biochemistry, Palacky University in Olomouc, Czech Republic
2013 – Ph.D. Student, Institute of Cancer Research, Medical University Vienna, Austria

Publications:

  1. Dolezel  P,  Koudelkova  P,  Mlejnek  P  (2010)  Halogenation  of  N⁶-benzyladenosine decreases its cytotoxicity in human leukemia cells, Toxicology in Vitro 24(8):2079-83

 

 

Claudia Bellomo, MSc

Claudia Bellomo, MScClaudia Bellomo was born in Italy, completed her Bachelor’s Degree in Healthcare and Pharmaceutical Biotechnology in 2008 and her Master Degree in Medical Biotechnology and Molecular Medicine in 2010 at the Faculty of Biotechnology, University of Bari. In 2008 she did her Bachelor Degree internship concerning “Cloning and expression in yeast gene encoding the protein Lpp2981 of L. Pneumophila Spp.” under the supervision of Dr. Carlo Marya Marobbio at the Pharmaceutical Biological Department, Faculty of Pharmacy, University of Bari. In 2010 she pursued her Master Degree internship focused on “Validation of drug nanocolloids and polyelectrolyte capsules as novel carriers for controlled drug delivery into ovarian cancer cells” at the Nanocarriers and Biomechanics Division of CNR- Nano and Di.Ste.Ba, University of Salento under the supervision of Prof. Susanna Cotecchia, Dr. Stefano Leporatti and Dr. Daniele Vergara. In 2011 she earned a prestigious scholarship given by Elite Network of Bavaria finalized to work as Research Assistant in the group of Prof. Thomas Bein at CENS- Center For Nanoscience, Ludwig Maximilians University, Munich where she dealt with Supported Lipid Bilayer as a pH sensitive cover of silica nanoparticles. She is currently working as PhD student in the group of Prof. Aristidis Moustakas at the Institute for Medical Biochemistry and Microbiology, Uppsala University.

2008    B.Sc, Healthcare and Pharmaceutical Biotechnology, Faculty of Biotechnology, University of Bari
2010    M.Sc, Medical Biotechnology and Molecular Medicine, Faculty of Biotechnology, University of Bari
2012    Research Assistant, Center for Nanoscience, Ludwigs- Maximilians University, Munich, Germany

Publications

  1. Vergara D, Bellomo C, Zhang X, Vergaro V, Tinelli A, Lorusso V, Rinaldi R, Lvov YM, Leporatti S, Maffia M. (2012)Lapatinib/Paclitaxel polyelectrolyte nanocapsules for overcoming multidrug resistance in ovarian cancer. Nanomedicine. 8(6), 891-9
  2. Vergaro V, Scarlino F, Bellomo C, Rinaldi R, Vergara D, Maffia M, Baldassarre F, Giannelli G, Zhang X, Lvov YM, Leporatti S. (2011) Drug-loaded polyelectrolyte microcapsules for sustained targeting of cancer cells. Advanced Drug Delivery Review. 63(9), 847-64.

 

 

 

Nemany Abdelhamid Nemany Hanafy, MSc.

Nemany Hanafi, MSc.  Nemany has got Bachelor Degree (with very good grade, 81.2%) in Biological Department -Science collage - Al Azhar University / Assuit. His graduation was in June, 2000. In   May 2002, nemany has studied Master courses   for one full time year (his grade was   very good) for giving him qualification   to apply for MSc research thesis. In May , 2005 , Nemany has applied for MSc degree in Biological Department / Zoology -Science Collage - Al azhar University / Cairo as collaborated   supervision with Cell biological laboratory - Atomic Force Authority . Through his thesis, he investigated the protective role of calcium channel blocker Verapamil against liver fibrosis, Necrosis and steatosis induced by CCl4 + Ethanol.


1996-2000 B.Sc, Biological Science, Science collage, Al azhar University

2002-2003 Pre-MSc, Biological Science, Science collage, Al azhar University

2005-2010 MSc (Researchthesis), Biological Science, Science collage, Al azhar University

2005-Now  Senior Lab, technician, Biological Science, Science Collage, Al azhar university

 

Publications

  1.  Safer, M. Afzal, A.Nomani, O.   Sosamma and Mousa " Curative propensity of green tea extract towards hepatic fibrosis induced by CCl4: A histopathological study" EXPERIMENTAL AND THERAPEUTIC MEDICINE 3: 781-786, 2012
  2. Hanaa Fathy Waer, NomaniAbdel HamidNomani and Eman Rizk Elbealy      "Ameliorated Effects of Verapamil on Hepatotoxicity Induced by Ethanol and Carbon Tetrachloride” J Cytol Histol Volume 3 , Issue 2 , 1000142.
  3. Abdel-Majeedsafer, M.Afzal, M.Nomani, S.A.Mousa "Green Tea Extract in the management of Hepatic Fibrosis” Tea in health and diseases,Elsevier, Chapter 76.

 

 

 

 

Yuan Cao

Yuan Cao

is currently working as PhD student in the group of Prof. Gianluigi Giannelli at the Department of Emergency and Organ Transplantation, Section of Internal Medicine, Allergology and Clinical Immunology, University of Bari. He was born in China, received his Bachelor Degree from Dalian Polytechnic Universityin China and his Master Degreefrom University of Sheffieldin the UK. In 2009, he did hisBachelor graduate project regarding“Analysis of Change of POD and PPO in Oilseed Rape Induced by SclerotiniaScleroterum”. In 2011, he did his Master research project pertaining to “HYDROMAX 1000: A study of surface wetting, anti-algal and anti-fungal properties” under the supervision of Prof. Peter Styring. His research intrests include Drug development &Delivery, Cancer Research, and Organ Transplantation.

2009  BSc Biotechnology, Faculty of Biological and Food Engineering,Dalian Polytechnic University

2011  MSc Biological and Bioprocess Engineering, Department of Chemical and Biological Engineering, Faculty of Engineering, University of Sheffield

 

Loubna Chadli, PhD

Loubna Chadli , MScThis Information will be added shortly !