Philip LoVerde, PhD, Professor
|Education:||1976 University of Michigan, Ph.D.|
|Cross Appointments:||Professor, Department of Pathology; Adjunct Scientist, Southwest National Primate Research Center|
|Other Faculty Positions:||2006-2011 Visiting Professor in the Department of Parasitology, Central South University Xiang-Ya School of Medicine, Changsha, Hunan, China |
2004-present Scientist, Southwest Foundation for Biomedical Research
2004- 2006 Scientific Director, Southwest Foundation for Biomedical Research (position eliminated)
2005-present SUNY Distinguished Professor Emeritus
2004 SUNY Distinguished Professor
1992-2004 Associate Chairman of Microbiology, State University of New York at Buffalo (SUNYAB)
1992-1994 Co Director, Center for Advanced Molecular Biology and Immunology
1989-2005 Professor of Pathology, SUNYAB, joint appointment
1988-2005 Professor of Microbiology, SUNYAB
Schistosomiasis is a major cause of morbidity in 76 countries of the world where it afflicts more than 200 million people. Our studies are aimed at elucidating molecular mechanisms of schistosome-host interactions. An understanding of the role schistosome genes and gene products play in these interactions will lead to vaccine candidates, improved diagnostics, and a basis for rationale drug design. One area of research is to characterize genes that encode antigens and to assess the role these antigens play in schistosome-host interactions. In this regard we have identified a number of genes that encode antigens associated with the outer covering (tegument) of larval schistosomes, the targets of immune killing, and elucidated their role in schistosome immunity. Using naked DNA vaccination strategies, we have identified several vaccine candidates such as filamin. Larval schistosome parasites are eliminated by a cell mediated cytotoxic response in which host cells like macrophages and eosinophils produce cidal oxidants. Our research has shown that adult worms which are able to evade the host immune response, have the highest level of antioxidant activity in terms of transcription and specific activity and the activity localizes to the tegument (outer covering) of the adult stage but not the larval stage. Using naked DNA vaccines we have demonstrated that forms of superoxide dismutase and glutathione peroxidase will consistently provide significant protection against schistosome infection. We have demonstrated for the first time that adult worms and not just the larval stages of the parasite can be a target for immune elimination. This has resulted in a major advance in schistosome vaccinology as previous studies have always focused on the larval stage as an immune target. Currently, we are evaluating the efficacy of filamin, SOD and GPX in baboons as a prelude to human clinical trials.
Pathogenesis is due to eggs (produced by mature female worms) that lodge in tissues and incite a granulomatous inflammatory reaction. It turns out that female schistosomes will not develop or become reproductively active without a direct stimulation by the male parasite. The male stimulus regulates the development of the vitelline cells of the female that supply the eggshell precursors and nutrients for embryonation. We have characterized two small gene families that each encode a major eggshell protein, and demonstrated that these genes are regulated in a stage-, tissue and temporal-specific manner in response to a male-stimulus. Currently, we are studying the signal pathways that the male stimulus might follow to regulate female-specific gene expression. In this regard we have been studying nuclear receptors (NR) and the TGF-beta signaling pathway. We have identified 21 NR in S. mansoni. Of these we have demonstrated by gel shift assay and the yeast one-hybrid system that NR of the RXR subfamily (SmRXR1 and SmRXR2), Constitutive Androstane Receptor (CAR), and fushi tarazu factor 1 (FTZ-F1) to be involved in the regulation of these eggshell precursor genes. As part of these studies, we are also elucidating the TGF-beta signaling pathway. We have isolated and characterized two BMP-like ligands, Type II and I TGF-beta receptor, SmSmads 1,2,4 and 8. We have been able to demonstrate by RNAi knockdown that human TGF-beta will bind to TBRII and transduce a signal to regulate a schistosome gene that encodes a gynecophoric canal protein. The gynecophoric canal protein is thought to play an important role in worm pairing. This coupled with our in situ hybridization and immunolocalization data that shows the presence TBRI, SmSmad 2, 4, and 8 in the vitelline cells suggests an important role for the TGF-beta pathway in female reproductive development. Our goal is to understand what genes and gene products contribute to female reproductive development and what factors in what manner regulate the expression of these genes. Our results to date have provided us with information on potential signaling pathways in the male-female interaction and in host-parasite interactions. As regards the latter, we are interested in what host molecules the parasite utilizes to transduce signals to regulate development, site finding behavior, immune evasion, reproductive activity, etc.
In addition to the above major projects, we also have a number of other collaborative projects. One long standing collaboration is with The Institute for Genomic Research (TIGR) and the Wellcome Trust-Sanger Institute to sequence the S. mansoni genome and contribute towards the development of a linkage and physical map. We have produced more than 8X coverage of the S. mansoni genome and are currently assembling and annotating the genome. As regards the genetic map, in a collaboration with Tim Anderson at the SFBR, we have developed over 300 microsatellite markers that we have mapped across the genome by mapping them to BAC clones that have been physically mapped to the various schistosome chromosomes. We have performed the genetic crosses and generated a 5cM map that will allow the schistosome community to identify genes responsible for various phenotypes such as drug resistance and virulence factors.
The overall focus in the lab is to understand the role genes and gene products play in schistosome-host interactions.
- Nuclear hormone receptors in parasitic helminths.
Wu W, LoVerde PT
Mol Cell Endocrinol: 2011-03-01; 334(1-2); 56-66 Epub: 2010-06-26.
PMID: 20600585   LINK:
- Signal transduction regulates schistosome reproductive biology.
LoVerde PT, Andrade LF, Oliveira G
Curr Opin Microbiol: 2009-08-01; 12(4); 422-8 Epub: 2009-07-04.
PMID: 19577949   LINK:
- Genomic linkage map of the human blood fluke Schistosoma mansoni.
Charles D. Criscione, Claudia L. L. Valentim, Hirohisa Hirai, Philip T. LoVerde, & Timothy J. C. Anderson
Genom Biol: 2009-06-30; 10(6);
- The Genome of the blood fluke Schistosoma mansoni.
Berriman, M., Haas, B.J., LoVerde, P.T., Wilson, R.A., Dillon, G.P. Cerqueira, G.C., Mashiyama, S.T., Al-Lazikani, B., Andrade, L.F., Ashton, P.D. Aslett, M.A., Bartholomeu, D.C., Blandin, G., Caffrey, C.R., Coghlan, A., Coulson, R., Day, T.A., Delcher,
Nature: 2009-01-01; 460(); 352-358
Complete Publication Listing