Project Scientist, UCSD
Skaggs School of Pharmacy and Pharmaceutical Sciences
Contact:
The microscopic world always fascinated me! To pursue this fascination as a career, I graduated in Biological Sciences (BA/Licentiate degree) in Federal University of Rio de Janeiro, and completed MSc and PhD in Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil. I completed a postdoctoral training in the Center for Discovery and Innovation in Parasitic Diseases (CDIPD). In the Dr. Podust laboratory, I am now involved in rational drug development for treatment of Chagas disease and primary amebic encephalitis (PAM) targeting ergosterol biosynthesis enzymes in Trypanosoma cruzi and Naegleria fowleri. Additionally, in collaboration with other researchers in CDIPD, I work on drug discovery/development against a variety of drug targets in T. cruzi. Another area of my expertise is T. cruzi-host cell interactions. The emphasis are on understanding the mechanisms of regulation of extracellular matrix expression during T. cruzi infection to advance treatment of heart fibrosis, a serious condition that affects chronic Chagas' disease patients.
PUBLICATIONS
Design, Synthesis, and Biological Evaluation of New 1-(Aryl-1 H-pyrrolyl)(phenyl)methyl-1 H-imidazole Derivatives as Antiprotozoal Agents. J Med Chem. 2019 Feb 14;62(3):1330-1347. doi: 10.1021/acs.jmedchem.8b01464. Epub 2019 Jan 23. Saccoliti F, Madia VN, Tudino V, De Leo A, Pescatori L, Messore A, De Vita D, Scipione L, Brun R, Kaiser M, Mäser P, Calvet CM, Jennings GK, Podust LM, Pepe G, Cirilli R, Faggi C, Di Marco A, Battista MR, Summa V, Costi R, Di Santo R.
Biological evaluation and structure-activity relationships of imidazole-based compounds as antiprotozoal agents. Eur J Med Chem. 2018 Aug 5;156:53-60. doi: 10.1016/j.ejmech.2018.06.063. Epub 2018 Jun 28. Saccoliti F, Madia VN, Tudino V, De Leo A, Pescatori L, Messore A, De Vita D, Scipione L, Brun R, Kaiser M, Mäser P, Calvet CM, Jennings GK, Podust LM, Costi R, Di Santo R.
CYP51 is an essential drug target for the treatment of primary amoebic meningoencephalitis (PAM). PLoS Negl Trop Dis. 2017 Dec 28;11(12):e0006104. doi: 10.1371/journal.pntd.0006104. eCollection 2017 Dec. Debnath A, Calvet CM, Jennings G, Zhou W, Aksenov A, Luth MR, Abagyan R, Nes WD, McKerrow JH, Podust LM.
4-aminopyridyl-based lead compounds targeting CYP51 prevent spontaneous parasite relapse in a chronic model and improve cardiac pathology in an acute model of Trypanosoma cruzi infection. PLoS Negl Trop Dis. 2017 Dec 27;11(12):e0006132. doi: 10.1371/journal.pntd.0006132. eCollection 2017 Dec. Calvet CM, Choi JY, Thomas D, Suzuki B, Hirata K, Lostracco-Johnson S, de Mesquita LB, Nogueira A, Meuser-Batista M, Silva TA, Siqueira-Neto JL, Roush WR, de Souza Pereira MC, McKerrow JH, Podust LM.
Rapid Chagas Disease Drug Target Discovery Using Directed Evolution in Drug-Sensitive Yeast. ACS Chem Biol. 2017 Feb 17;12(2):422-434. doi: 10.1021/acschembio.6b01037. Ottilie S, Goldgof GM, Calvet CM, Jennings GK, LaMonte G, Schenken J, Vigil E, Kumar P, McCall LI, Lopes ES, Gunawan F, Yang J, Suzuki Y, Siqueira-Neto JL, McKerrow JH, Amaro RE, Podust LM, Durrant JD, Winzeler EA.
Interactions between 4-aminoquinoline and heme: Promising mechanism against Trypanosoma cruzi. Int J Parasitol Drugs Drug Resist. 2016 Jul 14;6(3):154-164. doi: 10.1016/j.ijpddr.2016.07.001. [Epub ahead of print] Lechuga GC, Borges JC, Calvet CM, de Araújo HP, Zuma AA, do Nascimento SB, Motta MC, Bernardino AM, Pereira MC, Bourguignon SC.
TGF-β receptor type II costameric localization in cardiomyocytes and host cell TGF-β response is disrupted by Trypanosoma cruzi infection. Parasitology. 2016 May;143(6):704-15. doi: 10.1017/S0031182016000299. Epub 2016 Mar 21. Calvet CM, Silva TA, DE Melo TG, DE Araújo-Jorge TC, Pereira MC.
Hydroxamic acid derivatives: a promising scaffold for rational compound optimization in Chagas disease. J Enzyme Inhib Med Chem. 2016 Dec;31(6):964-73. doi: 10.3109/14756366.2015.1077330. Epub 2015 Aug 31. de Menezes Dda R, Calvet CM, Rodrigues GC, de Souza Pereira MC, Almeida IR, de Aguiar AP, Supuran CT, Vermelho AB.
Binding mode and potency of N-indolyloxopyridinyl-4-aminopropanyl-based inhibitors targeting Trypanosoma cruzi CYP51. J Med Chem. 2014 Dec 11;57(23):10162-75. doi: 10.1021/jm501568b. Epub 2014 Nov 25. Vieira DF, Choi JY, Calvet CM, Siqueira-Neto JL, Johnston JB, Kellar D, Gut J, Cameron MD, McKerrow JH, Roush WR, Podust LM.
4-Aminopyridyl-based CYP51 inhibitors as anti-Trypanosoma cruzi drug leads with improved pharmacokinetic profile and in vivo potency. J Med Chem. 2014 Aug 28;57(16):6989-7005. doi: 10.1021/jm500448u. Epub 2014 Aug 19. Calvet CM, Vieira DF, Choi JY, Kellar D, Cameron MD, Siqueira-Neto JL, Gut J, Johnston JB, Lin L, Khan S, McKerrow JH, Roush WR, Podust LM.
R-Configuration of 4-aminopyridyl-based inhibitors of CYP51 confers superior efficacy against Trypanosoma cruzi. ACS Med Chem Lett. 2014 Apr 10;5(4):434-9. doi: 10.1021/ml500010m. Choi JY, Calvet CM, Vieira DF, Gunatilleke SS, Cameron MD, McKerrow JH, Podust LM, Roush WR.
Rational development of 4-aminopyridyl-based inhibitors targeting Trypanosoma cruzi CYP51 as anti-chagas agents. J Med Chem. 2013 Oct 10;56(19):7651-68. doi: 10.1021/jm401067s. Epub 2013 Sep 30. Choi JY, Calvet CM, Gunatilleke SS, Ruiz C, Cameron MD, McKerrow JH, Podust LM, Roush WR.
Chemical-biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target. Beilstein J Org Chem. 2013;9:15-25. doi: 10.3762/bjoc.9.3. Epub 2013 Jan 4. Choy JW, Bryant C, Calvet CM, Doyle PS, Gunatilleke SS, Leung SS, Ang KK, Chen S, Gut J, Oses-Prieto JA, Johnston JB, Arkin MR, Burlingame AL, Taunton J, Jacobson MP, McKerrow JM, Podust LM, Renslo AR.
Current understanding of the Trypanosoma cruzi-cardiomyocyte interaction. Front Immunol. 2012;3:327. doi: 10.3389/fimmu.2012.00327. Calvet CM, Melo TG, Garzoni LR, Oliveira FO Jr, Neto DT, N S L M, Meirelles L, Pereira MC.
Diverse inhibitor chemotypes targeting Trypanosoma cruzi CYP51. PLoS Negl Trop Dis. 2012;6(7):e1736. doi: 10.1371/journal.pntd.0001736. Epub 2012 Jul 31. Gunatilleke SS, Calvet CM, Johnston JB, Chen CK, Erenburg G, Gut J, Engel JC, Ang KK, Mulvaney J, Chen S, Arkin MR, McKerrow JH, Podust LM.
Trypanosoma cruzi heparin-binding proteins mediate the adherence of epimastigotes to the midgut epithelial cells of Rhodnius prolixus. Parasitology. 2012 May;139(6):735-43. doi: 10.1017/S0031182011002344. Epub 2012 Feb 7. Oliveira FO Jr, Alves CR, Souza-Silva F, Calvet CM, Côrtes LM, Gonzalez MS, Toma L, Bouças RI, Nader HB, Pereira MC.
Involvement of host cell heparan sulfate proteoglycan in Trypanosoma cruzi amastigote attachment and invasion. Parasitology. 2011 Apr;138(5):593-601. doi: 10.1017/S0031182010001678. Epub 2011 Jan 27. Bambino-Medeiros R, Oliveira FO, Calvet CM, Vicente D, Toma L, Krieger MA, Meirelles MN, Pereira MC.
A comparative study of posaconazole and benznidazole in the prevention of heart damage and promotion of trypanocidal immune response in a murine model of Chagas disease. Int J Antimicrob Agents. 2010 Jul;36(1):79-83. doi: 10.1016/j.ijantimicag.2010.03.006. Epub 2010 May 7. Olivieri BP, Molina JT, de Castro SL, Pereira MC, Calvet CM, Urbina JA, Araújo-Jorge TC.
Regulation of extracellular matrix expression and distribution in Trypanosoma cruzi-infected cardiomyocytes. Int J Med Microbiol. 2009 Apr;299(4):301-12. doi: 10.1016/j.ijmm.2008.08.005. Epub 2008 Oct 16. Calvet CM, Oliveira FO Jr, Araújo-Jorge TC, Pereira MC.
Trypanosoma cruzi heparin-binding proteins and the nature of the host cell heparan sulfate-binding domain. Microb Pathog. 2008 Apr;44(4):329-38. Epub 2007 Oct 22. Oliveira FO Jr, Alves CR, Calvet CM, Toma L, Bouças RI, Nader HB, Castro Côrtes LM, Krieger MA, Meirelles Mde N, Souza Pereira MC.
SB-431542, a transforming growth factor beta inhibitor, impairs Trypanosoma cruzi infection in cardiomyocytes and parasite cycle completion. Antimicrob Agents Chemother. 2007 Aug;51(8):2905-10. Epub 2007 May 25. Waghabi MC, Keramidas M, Calvet CM, Meuser M, de Nazaré C Soeiro M, Mendonça-Lima L, Araújo-Jorge TC, Feige JJ, Bailly S.
Trypanosoma cruzi-cardiomyocyte interaction: role of fibronectin in the recognition process and extracellular matrix expression in vitro and in vivo. Exp Parasitol. 2004 May-Jun;107(1-2):20-30. Calvet CM, Meuser M, Almeida D, Meirelles MN, Pereira MC.
Heparan sulfate proteoglycans mediate the invasion of cardiomyocytes by Trypanosoma cruzi. J Eukaryot Microbiol. 2003 Mar-Apr;50(2):97-103. Calvet CM, Toma L, De Souza FR, Meirelles Mde N, Pereira MC.