Marcelo Ramalho-Ortigao

Research Assistant Professor

Doctor in Sciences, Oswaldo Cruz Institute 2000

Postdoctoral Training, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 2001-2005

Research Interests:

My overriding interests revolve around leishmaniases, protozoan diseases caused by parasites of the genus Leishmania, transmitted to the vertebrate host by the bite of an infected sand fly. Within the vector midgut, Leishmania undergoes a complex cycle culminating in the infectious metacyclic promastigote forms.

In contrast to malaria parasites, which invade the mosquito salivary glands for transmission, Leishmania remains in the sand fly gut, moving towards the foregut and mouth parts for transmission to a suitable host. As previous data have indicated, proteins produced in the sand fly midgut may have a significant role in the parasite development and my research interests involve the characterization of molecular interactions between sand fly vectors and Leishmania as well as physiological changes taking place in the midgut following a blood meal.

Understanding of the molecular events taking place during midgut interaction between Leishmania and its sand fly vector may lead to novel transmission blocking strategies, also known as transmission blocking vaccines or TBVs. Our approach relies on transcriptome analyses to identify and characterize sand fly genes potentially associated with parasite development.

We recently expanded our transcriptome studies to include other disease vectors, such as Aedes aegypti. In addition to the potential development of TBVs to fight off leishmaniasis, our group is also interested in role played by sand fly saliva in protection against Leishmania in vertebrates. Sand fly salivary gland homogenate have been shown to exacerbate legion development in animal models, and exposure to either salivary gland antigens or the bite of uninfected sand flies protect against disease development. Thus, the potential use of salivary gland molecules as vaccines is currently being sought.

Nevertheless, differences related to sand fly population variability still needs to be defined. Thus, we are also engaged in research focused on sand fly salivary gland variability and population structuring. Additionally, our lab is involved in the sand fly genome and ESTs projects currently under way. These two projects will generate a very large set of data pertaining to the genome and transcriptome of P. papatasi and may reveal novel clues about regulation of gene expression in sand flies.

Specific areas of investigation include:

The characterization of midgut proteins of sand fly vectors that might play a role in parasite survival and/or development.
Differential expression profiles of sand fly midgut
Functional genomics studies of the sand fly midgut
The use of midgut cDNAs and proteins as potential means to control parasite transmission
Sand fly salivary gland protein sequence variability and population genetics
Use of salivary gland antigens in anti-Leishmania vaccine development
Epidemiology and ecology of leishmaniasis

Current collaborative studies taking place in Brazil, at the Instituto Aggeu Magalhaes IOC-FIOCRUZ and Universidade Federal de Pernambuco (UFPE), in Recife, and at the Oswald Cruz Institute in Rio de Janeiro are aimed at sand fly population genetics and epidemiology of leishmaniasis in the Northeastern region of Brazil, characterization of insecticide resistance genes, and characterization of ESTs from the principal visceral leishmaniasis vector Lutzomyia longipalpis in Brazil. Another collaborative study, with the Renne Rachou Institute in Belo Horizonte, is aimed at investigating the molecular basis for DEN2 virus susceptibility in Ae. aegypti.

Relevant publications

1. Pitaluga AN, Beteille V, Lobo AR, Farias JRO, Dávila AMR, Souza AA, Ramalho-Ortigão JM, Traub-Cseko YM. EST sequencing of blood-fed and Leishmania-infected gut of Lutzomyia longipalpis, the principal visceral leishmaniasis vector in the Americas. BMC Genomics, In Review.

2. Jayakumar A, Donovan MJ, Ramalho-Ortigao M, McDowell MA. Leishmania major induced interleukin-12 expression in human dendritic cells is mediated by NFkB, IRF-1 and IRF-8. Infect Immunity, In review.

3. Coutinho-Abreu IV, Balbino VQ, Sonoda IV, Fonseca JA, Melo MA, Ramalho-Ortigão M. The role of ongoing gene flow and shared ancestral polymorphisms in the genetic structuring of Lutzomyia longipalpis populations in Eastern Brazil. Med Vet Entomol, In review.

4. Telleria EL, Ortigão-Farias JR, Araújo APO, Pitaluga AN, Ramalho-Ortigão JM, Traub-Cseko YM (2007). Constitutive and blood meal induced trypsin genes in Lutzomyia longipalpis. Arch Insect Biochem Physiol 66(2):53-63.

5. Ramalho-Ortigão JM, Jochim RC, Kamhawi S, Anderson JM, Lawyer PG, Pham V, Valenzuela JG, (2007). Exploring the midgut transcriptome of the sandfly Phlebotomus papatasi: Expression profile of sugar-fed, blood-fed and Leishmania major-infected sandfly midgut. BMC Genomics, Aug 30;8(1):300 [Epub ahead of print].

6. Ramalho-Ortigão JM, Pitaluga, AN, Telleria EL, Marques C, Souza AA, Traub-Cseko YM (2007). Cloning and characterization of a V-ATPase subunit C from the American visceral leishmaniasis vector Lutzomyia longipalpis modulated during development and blood ingestion. Mem Inst Oswaldo Cruz 102(4):509-515.

7. Coutinho-Abreu IV, Valenzuela JG, Sonoda IV, Balbino VQ, Ramalho-Ortigao M (2007). Structural Characterization of Acetylcholinesterase 1 from the Sand Fly Lutzomyia longipalpis. J. Med Entomol 44(4): 639-650.

8. Genetic structure of natural populations of the sand fly Lutzomyia longipalpis (Diptera: Psychodidae) from the Brazilian Northeastern Region (2006). Balbino VQ, Coutinho-Abreu IV, Sonoda IV, Melo MA, Andrade PP, Castro JAF, Rebêlo JM, Carvalho SM, Ramalho-Ortigão M. Acta Tropica, 98 (1), 15-24.

9. Ramalho-Ortigão JM, Kamhawi S, Manju J, Reynoso D, Lawyer PG, Dwyer DM, Sacks DL, Valenzuela JG (2005). Characterization of a blood activated chitinolytic system in the midgut of the sand fly vectors L. longipalpis and P. papatasi. Insect Mol Biol, 14 (6), 703–712.

10. Kamhawi S, Ramalho-Ortigão M, Pham VM, Kumar S, Lawyer PG, Turco SJ, Barrilas-Mury C, Sacks D, Valenzuela JG (2004) A Role for Insect Galectins in Parasite Survival. Cell, Vol. 119, 329-341.

11. Ramalho-Ortigão JM, Traub-Cseko YM (2003). Molecular characterization of Llchit1, a midgut chitinase cDNA from the leishmaniasis vector Lutzomyia longipalpis. Insect Biochem Mol Biol 33, 279-87.

12. Ramalho-Ortigão JM, Kamhawi S, Rowton ED, Ribeiro JM, Valenzuela JG (2003). Cloning and characterization of trypsin- and chymotrypsin-like proteases from the midgut of the sand fly vector Phlebotomus papatasi. Insect Biochem Mol Biol 33, 163-71.

13. Ramalho-Ortigão JM, Temporal P, Oliveira SMD, Barbosa AF, Vilela ML, Rangel EF, Brazil RP, Traub-CsekoYM (2001). Characterization of expressed sequence tags and differentially expressed mRNAs from the sand fly vector Lutzomyia longipalpis. Mem Inst Oswaldo Cruz 96, 105-111.

14. Traub-Cseko YM, Ramalho-Ortigão JM, Dantas AP, De Castro SL, Barbosa HS, Downing KH (2001). Dinitroaniline herbicides against protozoan parasites: the case of Trypanosoma cruzi. Trends in Parasitol 17, 136-141.