Laboratory of Immunology-Parasitology
The Laboratory of Immunology-Parasitology is unique in Italy and one of the few in Europe working on the identification, screening and early development of new drugs and new targets against malaria and lehismaniasis. Both diseases, induced by protozoan parasites, cause more than 220 millions cases/year with frequent co-infections, and an overall mortality of about 500,000 people, especially children. Malaria and Leishmaniasis are considered Neglected Tropical Diseases for their spread in poor countries, the limited investments in R&D and the low number of effective drugs available.
The main research topics of the laboratory of Immunology-Parasitology are as follows.
- Identification and early development of synthetic compounds or natural products with activity against sexual and asexual stages of Plasmodium falciparum and against both the amastigote and the promastigotes forms of Leishmania spp.
- Study of the mechanism of action, cellular and bone marrow toxicities and risk of inducing resistance of potential new drugs.
- Studies on the innate immune responses and the pathogenesis of severe malaria and leishmaniasis, and co-infections: analysis of the role of parasites and their products on macrophage activation, cytokines production or activation of endothelial cells in in vitro and ex vivo models of angiogenesis. The aim is to identify new molecular targets for new drugs or new immunotherapies to be used in combination with current drugs.
In vitro cultures of wild-type and transgenic strains of P. falciparum in both asexual and sexual stages are available, as well as wild-type and transgenic strains of Leishmania (L. infantum, L. tropica, L. braziliensis) both promastigote and amastigote forms. Chemosensitivity assays with spectrophotometric, fluorimetric or luminescent detection are available on a Medium Throughput Screening (MTS) (Tecan Evo75) platform.
In vitro human or murine, cell lines are used for cytotoxicity, immunological and angiogenesis assays. Other available techniques are ELISA, cytofluorimetry (FACS), fluorescent microscopy. Basic biochemical and molecular techniques, like protein, lipid, DNA and RNA extractions, gel electrophoresis, Polymerase Chain Reaction, Western Blot and the technological platforms of UNIMI are also available (Imaging, Electronic and Confocal Microscopy and MS/MS).
The Laboratory is a network on its own because at present, it includes researchers moved to different Departments of UNIMI: Prof Nicoletta Basilico, who significantly contributed to create and expand the malariology group at DiSFeB, now directs the Leishmaniosis Lab at DiSBIOC, working with Dr. Silvia Parapini and Dr Sarah D’Alessandro. Dr. Yolanda Corbett is now in the Dept of Bioscience. Long term collaborations with researchers of several UNIMI Departments, including those of the Faculty of Pharmacy, DiSFeB and DISFARM, are on going. In Italy, the Laboratory is part of the Italian Malaria Network (Centro Interuniversitario di Ricerche sulla Malaria, CIRM), a virtual research Centre which includes ten Italian universities and the Istituto Superiore di Sanità.
At the International level, the Laboratory collaborates with WHO, Medicine for Malaria Venture (MMV, www.mmv.org), the Bill & Melinda Gates Foundation, European networks (COST Actions, FP-6 EU-ANTIMAL, FP7), African networks and Universities in Burkina Faso and South Africa, and in Asia, Universities of Macau, Bangkok and Pune.
- Scaccabarozzi D, Deroost K, Corbett Y, Lays N, Corsetto P, Salè FO, Van den Steen PE, Taramelli D. - Differential induction of malaria liver pathology in mice infected with Plasmodium chabaudi AS or Plasmodium berghei NK65- Malar J. 2018 9;17:18.
- Basilico N, Parapini S, Sparatore A, Romeo S, Misiano P, Vivas L, Yardley V, Croft SL, Habluetzel A, Lucantoni L, Renia L, Russell B, Suwanarusk R, Nosten F, Dondio G, Bigogno C, Jabes D, Taramelli D. -In Vivo and In Vitro Activities and ADME-Tox Profile of a Quinolizidine-Modified 4-Aminoquinoline: A Potent Anti-P. falciparum and Anti-P. vivax Blood-StageAntimalarial -Molecules.2017;22(12).pii:E2102.
- Parapini S, Olliaro P, Navaratnam V, Taramelli D, Basilico N. Stability of the antimalarial drug dihydroartemisinin under physiologically-relevant conditions: implications for clinical treatment, pharmacokinetic and in vitro assays. Antimicrob Agents Chemother. 2015 Jul;59(7):4046-52. doi: 10.1128/AAC.00183-15.
- 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. J Antimicrob Chemother. 2013 Sep;68(9):2048-58. doi:10.1093/jac/dkt165.
- Finaurini S, Basilico N, Corbett Y, D'Alessandro S, Parapini S, Olliaro P,Haynes RK, Taramelli D. Dihydroartemisinin inhibits the human erythroid cell differentiation by altering the cell cycle. Toxicology. 2012 Oct9;300(1-2):57-66.