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Laboratory of Parasitology and Immunology  

Lab. Taramelli

 

Chief  Prof. Donatella Taramelli  donatella.taramelli@unimi.it

Team
Silvia Parapini Associate Researcher silvia.parapini@unimi.it
Yolanda Corbett Post doc yolanda.corbett@unimi.it
Sarah D’Alessandro Post doc sarah.dalessandro@unimi.it
Denise Ilboudo Post doc denise.ilboudo@unimi.it
Paola Misiano Post doc paola.misiano@unimi.it
Diletta Scaccabarozzi PhD studentdiletta.scaccabarozzi@unimi.it

Associated Laboratory at DiSBiCO
Nicoletta Basilico Senior Researcher nicoletta.basilico@unimi.it

 

Research areas

The laboratory of Parasitology and Immunology is unique in Italy and one of the few in Europe involved in studies for the identification and early development of new anti-parasitic drugs, particularly anti-malaria and anti-leishmania compounds. Research is directed to the analysis of the molecular and cellular basis of drug action and toxicity, including the mechanism of resistance. In addition, studies are conducted on the pathogenesis of severe malaria anemia and cerebral malaria and on the role played by the innate immune response to the parasites. The laboratory has the facilities for culturing the sexual and asexual stages of Plasmodium falciparum and a robotized medium throughput screening (MTS) platform for testing activity and toxicity of new compounds or natural products. In vitro cultures of amastigotes and promastigotes of Leishmania infantum are also available. The laboratory is linked to a large national and international collaborative network which includes the Italian Malaria Network (CIRM, Centro Interuniversitario di ricerche sulla Malaria), as well as WHO, Medicine for Malaria Venture (MMV, www.mmv.org ), European network (EU- Antimal, www.antimal.eu), the Bill & Melinda Gates Foundation. In addition, the laboratory works in direct collaboration with the group of Dr. Nicoletta Basilico, which was one of the founder and organiser of the malariology group and that now directs the laboratory of Leishmaniosis in the Department of Biomedical, Surgical and Dental Sciences at UNIMI.

The research topics can be summarised as follows 

  1. Identification and early development of synthetic compounds or natural products with antimalarial activity  against sexual and asexual stages of Plasmodium falciparum
  2. Identification and early development of synthetic compounds or natural products with activity  against amastigotes and promastigotes of Leishmania parasites
  3. Understanding the chemical, molecular and cellular basis of drug action and drug resistance
  4. Studies of cellular or bone marrow (erythropoiesis, angiogenesis) toxicity  by novel drugs.
  5. Studies of innate immunity in malaria: immunomodulatory role of malaria parasites or their products (hemozoin), or of antimalarial drugs on the response of macrophages or human endothelial cells in  in vitro o ex vivo models of angiogenesis.
  6. Studies of severe malaria pathogenesis: mechanisms of severe anemia, changes in the lipid metabolism in malaria ARDS; changes in the blood brain barrier (BBB) functions in cerebral malaria.

 

Technical Platforms

Biology and Cellular Immunology: in vitro culture of normal and transgenic strains of P. falciparum; in vitro culture of Leishmania infantum promastigotes and intracellular amastigotes; robotized medium-high throughput chemosensitivity assays (MTS) against P. falciparum and L. infantum at different stages; human and murine cell cultures; test of proliferation and cytotoxicity; In vitro model of human erythroid differentiation using peripheral human stem cells or cell lines; assays of tubulogenesis/angiogenesis on collagen matrices; Production and screening for cytokines, chemokines by ELISA or RTPCR. Most of the above mentioned techniques are based on spectrophotometric, luminometric or fluorimetric measurements; Phenotype analysis by cytofluorimetry (FACS) and fluorescent microscopy.

Biochemistry and Molecular Biology: Protein, lipids, DNA, RNA extraction; Gel electrophoresis; Polymerase Chain Reaction (PCR); basic technique of gene cloning; Western Blot. Analysis of cell membranes, lipid components and lipid identification (TLC, HPLC).

 

Selected publications

  1. D'Alessandro S, Silvestrini F, Dechering K, Corbett Y, Parapini S, Timmerman M, Galastri L, Basilico N, Sauerwein R, Alano P, Taramelli D. A Plasmodium falciparum screening assay for anti-gametocyte drugs based on parasite lactate dehydrogenase detection. Journal of Antimicrobial Chemotherapy 2013; doi: 10.1093/jac/dkt165. IF=5.068
  2. Ilboudo DP, Basilico N, Parapini S, Corbett Y, D'Alessandro S, Dell'agli M, Coghi P, Karou SD, Sawadogo R, Gnoula C, Simpore J, Nikiema JB, Monti D, Bosisio E, Taramelli D. Antiplasmodial and anti-inflammatory activities of Canthium henriquesianum (K. Schum), a plant used in traditional medicine in Burkina Faso. J Ethnopharmacol. 2013 May 13.
  3. Prato M, D'Alessandro S, Van den Steen PE, Opdenakker G, Arese P, Taramelli D, Basilico N. Natural haemozoin modulates matrix metalloproteinases and induces morphological changes in human microvascular endothelium. Cell Microbiol. 2011 Aug;13(8):1275-85.  IF  5.625
  4. D'Alessandro S, Basilico N, Corbett Y, Scaccabarozzi D, Omodeo-Salè F. Saresella M, Marventano I, Vaillant M, Olliaro P, Taramelli D. Hypoxia modulates  the effect of dihydroartemisinin on endothelial cells. Biochem Pharmacol.  2011 Sep 1;82(5):476-84. IF  4.889
  5. Finaurini S, Ronzoni L, Colancecco A, Cattaneo A, Cappellini MD, Ward SA, Taramelli D. Selective toxicity of dihydroartemisinin on human CD34+ erythroid cell differentiation. Toxicology. 2010 Oct 9;276(2):128-34.  IF  3.641
  6. Basilico N, Cortelezzi L, Serpellini C, Taramelli D, Omodeo-Salè F. Two complementary fluorimetric assays for the determination of aminoquinoline binding and uptake by human erythrocytes in vitro. Anal Biochem. 2009 Feb15;385(2):371-3. Epub 2008 Nov 13. IF 3.287
  7. D'Alessandro S, Gelati M, Basilico N, Parati EA, Haynes RK, Taramelli D. Differential effects on angiogenesis of two antimalarial compounds,dihydroartemisinin and artemisone: Implications for embryotoxicity.Toxicology. 2007 Nov 20;241(1-2):66-74. IF 2.919
  8. Parapini S, N Basilico, Monica Mondani, Piero Olliaro, D.Taramelli and  DiegoMonti Evidence that haem iron in the malaria parasite is not needed for the antimalarial effects of artemisinin.FEBS Letters 2004 ,575: 91-94 IF  3.843
  9. Omodeo-Sale', F., Motti, A., Basilico, N., Parapini, S., Olliaro, P., Taramelli, D. Accelerated senescence of human erythrocytes in culture with Plasmodium falciparum Blood, 102, 705-711, 2003, IF 10.120
  10. Parapini, S., Basilico, N., Pasini, E., Egan, T., Olliaro, P., Taramelli, D., Monti, D. Standardization of the physico-chemical parameters to asses in vitro the ß-Hematin Inhibitory Activity (BHIA) of antimalarial drugs. Experiment. Parasitol.2000, 96:249-256.

 

Patents
Italian Patent application N. MI2003A002044 (21/10/2003); International P.C.T. Appl. N. P.C.T./IB2004/003393 (18/10/2004)

Link to
Dipartimento di Scienze Biomediche, Chirurgiche e Odontoiatriche, nicoletta.basilico@unimi.it
www.crimalddi.eu
www.natsyndrugs.org

 

 

 

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