Daniela Cesselli

Dr. Cesselli

  

Associate Researcher and Coordinator of the MONALISA Medical research group within the  European Grant, 7FP, Ideas,ERC Advanced Grant ”Molecular Nanotechnology For Life Science Application: QUantitative Interactomics for Diagnostics, Proteomics and QUantitative Oncology,(Quidroquo) proposal n. 269025. P.I. Prof. G. Scoles

e-mail: daniela.cesselli@uniud.it

Address: University of Udine - DSMB - P.le S.Maria della Misericordia, 15 - 33100 Udine

Project description

The project overall aims to develop and apply the most innovative technologies for the understanding of highly debilitating and fatal diseases, such as cancer, heart disease and neurodegenerative diseases. Since nanotechnologies are particularly suitable for analytes and events that are small in number (e.g. stem cells and circulating tumor cells), or size (e.g. exosomes) or concentration (e.g. circulating miRNAs), we are exploring our clinical issues taking advantage of nano-devices for the study of patient-derived stem cells, exosomes and miRNAs. The ultimate goal is therefore to profoundly affect the life of patients by improving diagnostics, providing new prognostic systems and improving the criteria for the choice of the therapeutic strategy, pursuing, as much as possible, a personalized patient-based approach. 

RESULTS

In these years we were involved in:

  1. Supporting the development of a DNA nanoarray-based biosensor for detecting proteins in glioma-initiating stem cells by participating in: a. selection of the functionalization strategy, b. calibration of the devices and c. analytical validation (reliability and consistency of the bioanalitical performance) of the devices including the comparison with the gold-standard methods (Ganau et al., 2015)
  2. Glioma: a. we demonstrated that the microenvironment of glioma hosts non-tumorigenic stem cells (named glioma associated stem cells –GASC-) that can increase the biological aggressiveness of glioma-initiating cells through the release of nanovesicles named exosomes. A score, based on the expression of 9 proteins on the GASC surface, resulted to be the strongest available predictor of low-grade glioma patients’ prognosis (Bourkoula et al., 2014). b. We have studied cell deformability and interactions between glioma-initiating stem cells and glioma-associated-stem cells by atomic force microscopy and single cell force spectroscopy highlighting that the grade of GASC plays an important role in modulating cancer cell adhesion, which could affect glioma cell migration, invasion and thus cancer aggressiveness (Andolfi et al, 2014). c. We have identified via nanobody-based reverse proteomics of human glioma-initiating stem cells possible novel human glioblastoma biomarkers (Jovcevska I et al., 2014).
  3. Neurodegenerative diseases: taking advantage of the plasticity of adult stem cells isolated from the adipose tissue (an easily accessible source), it has been obtained a patient-based in vitro model of a neurodegenerative disease, the Niemann-Pick C (Bergamin N et al., 2013). Additionally, we studied the role of Ape-REF1 in the neural differentiation of stem cells demonstrating that the modulation of the Redox function of this protein through a small molecule can improve the neuron differentiation and direct it through specific subtypes (Domenis et al, 2014).
  4. Heart failure: We have previously shown that Cardiac Stem Cells (CSC) from explanted de-compensated hearts (E-CSC) are, with respect to those obtained from healthy donors (D-CSC), senescent and functionally impaired (Cesselli et al., 2013). More recently, we have shown that a molecular mechanim involving the impairment of AMPK activation followed by an arrest of the autophagic flux, the activation of the inflammasome, the increased release of IL1ß secretion and a reduced activation of Akt and CREB characterizes cardiac stem cell senescence. A pharmacological treatment able to restore the autophagic flux can reverse these molecular alterations and results in decreased cardiac stem cell senescence, thus improving their in vivo regenerative potential (E. Avolio et al., 2014; Gianfranceschi et al, submitted paper). Moreover, preliminary results have identified circulating miRNAs that can be used as biomarkers to stratify patients with heart failure (unpublished data). 
  5. Circulating Tumor Cells (CTC): We have developed a strategy to enrich blood samples, obtained from metastatic breast cancer patients, in CTCs that does not rely on the use of epithelial markers. Taking advantage of the DEPArray® system, we have identified and sorted, on the basis of a multiparametric fluorescence analysis, single, viable epithelial-like CTCs as well as CTCs in epithelial-to-mesenchymal transition. Purity and viability of the collected cells allowed both DNA and mRNA downstream analyses. We are clinically validating the value of CTC counting in metastatic breast cancer patients in collaboration with both the IOV of Padua (Dr. R. Zamarchi) and the University of Udine (Dr. F. Puglisi) (Bulfoni et al. 2016).

Full CV HERE

 Recent Publications (since 2012, full list here):

1.              Bulfoni M, Gerratana L, Del Ben F, Marzinotto S, Sorrentino M, Turetta M, Scoles G, Toffoletto B, Isola M, Beltrami CA, Di Loreto C, Beltrami AP, Puglisi F, Cesselli D. In patients with metastatic breast cancer the identification of circulating tumor cells in epithelial-to-mesenchymal transition is associated with a poor prognosis. Breast Cancer Res. 2016;18(1):30.

2.              Venturelli L, Nappini S, Bulfoni M, Gianfranceschi G, Dal Zilio S, Coceano G, Del Ben F, Turetta M, Scoles G, Vaccari L, Cesselli D, Cojoc D. Glucose is a key driver for GLUT1-mediated nanoparticles internalization in breast cancer cells. Sci Rep. 2016;6:21629.

3.              Rapozzi V, Ragno D, Guerrini A, Ferroni C, Pietra ED, Cesselli D, Castoria G, Di Donato M, Saracino E, Benfenati V, Varchi G. Androgen Receptor Targeted Conjugate for Bimodal Photodynamic Therapy of Prostate Cancer in Vitro. Bioconjug Chem. 2015.

4.              Meloni M, Cesselli D, Caporali A, Mangialardi G, Avolio E, Reni C, Fortunato O, Martini S, Madeddu P, Valgimigli M, Nikolaev E, Kaczmarek L, Angelini GD, Beltrami AP, Emanueli C. Cardiac Nerve Growth Factor Overexpression Induces Bone Marrow-derived Progenitor Cells Mobilization and Homing to the Infarcted Heart. Mol Ther. 2015.

5.              Gianfranceschi G, Gri G, Cesselli D, Beltrami AP. Stem Cell Senescence as the Memory of Past Injuries. Current Pathobiology Reports. 2015;3(1):17-26.

6.              Ganau M, Bosco A, Palma A, Corvaglia S, Parisse P, Fruk L, Beltrami AP, Cesselli D, Casalis L, Scoles G. A DNA-based nano-immunoassay for the label-free detection of glial fibrillary acidic protein in multicell lysates. Nanomedicine. 2015;11(2):293-300.

7.              Domenis R, Lazzaro L, Calabrese S, Mangoni D, Gallelli A, Bourkoula E, Manini I, Bergamin N, Toffoletto B, Beltrami CA, Beltrami AP, Cesselli D, Parodi PC. Adipose tissue derived stem cells: in vitro and in vivo analysis of a standard and three commercially available cell-assisted lipotransfer techniques. Stem Cell Res Ther. 2015;6(1):2.

8.              Avolio E, Meloni M, Spencer HL, Riu F, Katare R, Mangialardi G, Oikawa A, Rodriguez-Arabaolaza I, Dang Z, Mitchell K, Reni C, Alvino VV, Rowlinson JM, Livi U, Cesselli D, Angelini G, Emanueli C, Beltrami AP, Madeddu PR. Combined Intramyocardial Delivery of Human Pericytes and Cardiac Stem Cells Additively Improves the Healing of Mouse Infarcted Hearts Through Stimulation of Vascular and Muscular Repair. Circ Res. 2015.

9.              Verardo R, Piazza S, Klaric E, Ciani Y, Bussadori G, Marzinotto S, Mariuzzi L, Cesselli D, Beltrami AP, Mano M, Itoh M, Kawaji H, Lassmann T, Carninci P, Hayashizaki Y, Forrest AR, Beltrami CA, Schneider C. Specific mesothelial signature marks the heterogeneity of mesenchymal stem cells from high-grade serous ovarian cancer. Stem Cells. 2014;32(11):2998-3011.

10.           Mion F, Tonon S, Toffoletto B, Cesselli D, Pucillo CE, Vitale G. IL-10 production by B cells is differentially regulated by immune-mediated and infectious stimuli and requires p38 activation. Mol Immunol. 2014.

11.           Magini A, Polchi A, Tancini B, Urbanelli L, Di Cristina M, Mannucci R, Nicoletti I, Emiliani C. Methods to discriminate the distribution of acidic glycohydrolases between the endosomal-lysosomal systems and the plasma membrane. Methods Enzymol. 2014;534:25-45.

12.           Jovcevska I, Zupanec N, Kocevar N, Cesselli D, Podergajs N, Stokin CL, Myers MP, Muyldermans S, Ghassabeh GH, Motaln H, Ruaro ME, Bourkoula E, Turnsek TL, Komel R. TRIM28 and beta-actin identified via nanobody-based reverse proteomics approach as possible human glioblastoma biomarkers. PLoS One. 2014;9(11):e113688.

13.           Fortini C, Cesselli D, Beltrami AP, Bergamin N, Caragnano A, Moretti L, Cecaro F, Aquila G, Rizzo P, Riberti C, Tavazzi L, Fucili A, Beltrami CA, Ferrari R. Alteration of Notch signaling and functionality of adipose tissue derived mesenchymal stem cells in heart failure. Int J Cardiol. 2014.

14.           Domenis R, Bergamin N, Gianfranceschi G, Vascotto C, Romanello M, Rigo S, Vagnarelli G, Faggiani M, Parodi P, Kelley MR, Beltrami CA, Cesselli D, Tell G, Beltrami AP. The redox function of APE1 is involved in the differentiation process of stem cells toward a neuronal cell fate. PLoS One. 2014;9(2):e89232.

15.           Cesselli D, Beltrami AP. Stem cell senescence in diabetes: forgetting the sweet old memories. Diabetes. 2014;63(6):1841-1843.

16.           Bourkoula E, Mangoni D, Ius T, Pucer A, Isola M, Musiello D, Marzinotto S, Toffoletto B, Sorrentino M, Palma A, Caponnetto F, Gregoraci G, Vindigni M, Pizzolitto S, Falconieri G, De Maglio G, Pecile V, Ruaro ME, Gri G, Parisse P, Casalis L, Scoles G, Skrap M, Beltrami CA, Beltrami AP, Cesselli D. Glioma-associated stem cells: a novel class of tumor-supporting cells able to predict prognosis of human low-grade gliomas. Stem Cells. 2014;32(5):1239-1253.

17.           Avolio E, Gianfranceschi G, Cesselli D, Caragnano A, Athanasakis E, Katare R, Meloni M, Palma A, Barchiesi A, Vascotto C, Toffoletto B, Mazzega E, Finato N, Aresu G, Livi U, Emanueli C, Scoles G, Beltrami CA, Madeddu P, Beltrami AP. Ex vivo molecular rejuvenation improves the therapeutic activity of senescent human cardiac stem cells in a mouse model of myocardial infarction. Stem Cells. 2014.

18.           Andolfi L, Bourkoula E, Migliorini E, Palma A, Pucer A, Skrap M, Scoles G, Beltrami AP, Cesselli D, Lazzarino M. Investigation of adhesion and mechanical properties of human glioma cells by single cell force spectroscopy and atomic force microscopy. PLoS One. 2014;9(11):e112582.

19.           Zeppieri M, Salvetat ML, Beltrami AP, Cesselli D, Bergamin N, Russo R, Cavaliere F, Varano GP, Alcalde I, Merayo J, Brusini P, Beltrami CA, Parodi PC. Human adipose-derived stem cells for the treatment of chemically burned rat cornea: preliminary results. Curr Eye Res. 2013;38(4):451-463.

20.           Magini A, Polchi A, Urbanelli L, Cesselli D, Beltrami A, Tancini B, Emiliani C. TFEB activation promotes the recruitment of lysosomal glycohydrolases Œ≤-hexosaminidase and Œ≤-galactosidase to the plasma membrane. Biochemical and Biophysical Research Communications. 2013(0).

21.           Katare R, Oikawa A, Cesselli D, Beltrami AP, Avolio E, Muthukrishnan D, Munasinghe PE, Angelini G, Emanueli C, Madeddu P. Boosting the pentose phosphate pathway restores cardiac progenitor cell availability in diabetes. Cardiovasc Res. 2013;97(1):55-65.

22.           Garrovo C, Bergamin N, Bates D, Cesselli D, Beltrami AP, Lorenzon A, Ferrari R, Alberto Beltrami C, Lorusso V, Biffi S. In vivo tracking of murine adipose tissue-derived multipotent adult stem cells and ex vivo cross-validation. Int J Mol Imaging. 2013;2013:426961.

23.           Cesselli D, D'Aurizio F, Marcon P, Bergamin N, Beltrami CA, Beltrami AP. Cardiac stem cell senescence. Methods Mol Biol. 2013;976:81-97.

24.           Bergamin N, Dardis A, Beltrami A, Cesselli D, Rigo S, Zampieri S, Domenis R, Bembi B, Beltrami CA. A human neuronal model of Niemann Pick C disease developed from stem cells isolated from patient's skin. Orphanet J Rare Dis. 2013;8(1):34.

25.           Ferro F, Spelat R, D'Aurizio F, Puppato E, Pandolfi M, Beltrami AP, Cesselli D, Falini G, Beltrami CA, Curcio F. Dental pulp stem cells differentiation reveals new insights in Oct4A dynamics. PLoS One. 2012;7(7):e41774.

26.           Ferro F, Spelat R, D'Aurizio F, Falini G, De Pol I, Pandolfi M, Beltrami AP, Cesselli D, Beltrami CA, Curcio F. Acellular bone colonization and aggregate culture conditions diversely influence murine periosteum mesenchymal stem cell differentiation potential in long-term in vitro osteoinductive conditions. Tissue Eng Part A. 2012;18(13-14):1509-1519.

27.           Ferro F, Spelat R, Beltrami AP, Cesselli D, Curcio F. Isolation and characterization of human dental pulp derived stem cells by using media containing low human serum percentage as clinical grade substitutes for bovine serum. PLoS One. 2012;7(11):e48945.

28.           Beltrami AP, Cesselli D, Beltrami CA. Stem cell senescence and regenerative paradigms. Clin Pharmacol Ther. 2012;91(1):21-29.

29.           Beltrami A, Cesselli D, Beltrami C. Cardiac Resident Stem Cells: Work (Still) in Progress. J Stem Cell Res Ther 2012;S9:001.

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30.           Amadesi S, Reni C, Katare R, Meloni M, Oikawa A, Beltrami AP, Avolio E, Cesselli D, Fortunato O, Spinetti G, Ascione R, Cangiano E, Valgimigli M, Hunt SP, Emanueli C, Madeddu P. Role for substance p-based nociceptive signaling in progenitor cell activation and angiogenesis during ischemia in mice and in human subjects. Circulation. 2012;125(14):1774-1786, S1771-1719.

Monalisa Group

Department of Medical and Biological Sciences - University of Udine - Piazzale Kolbe, 4 - 33100 Udine - Italy

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