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
|Awards and Academic Honors:||2011 Commencement address; Graduate School of Biomedical Sciences, UTHSCSA |
Bill Stone Distinguished Lecturer, South Texas Blood and Tissue Center, San Antonio, 2006
Distinguished Professor, the highest faculty designation of the State Uversity of New York, 2004
President, American Society of Parasitologists (ASP), 2000-2001
Stockton Kimball Award for excellence in research, teaching, and citizenry by the School of Medicine and Biomedical Sciences, SUNY, May 26, 1993.
Henry Baldwin Ward Medal for the highest recognition of professional accomplishment given by the American Society of Parasitologists, 1989.
The Chester A. Herrick Award presented at the Annual Midwest Conference of Parasitologists for Demonstration of Outstanding Graduate Research sponsored by Eli Lilly & Company, 1974.
|Personal Statement:||My research involves studies of host-parasite interactions of Schistosoma mansoni and its hosts. I have more than 40-years of experience in field and bench research with schistosomiasis. The strengths of the lab are in molecular parasitology, immunoparasitology and genetics. We have contributed continuously to the molecular and genetic studies on Schistosoma. My research has always involved collaborations for bench and field research. Currently, Drs. Anderson, Hart, McHardy and LoVerde have a very strong and complementary collaboration that resulted in a Science paper and a grant proposal (4 %tile). I take an active role in field research in endemic countries having worked in Egypt for 30yrs, Brazil for >20 years and Kenya. Currently I am involved in a field study in Brazil to identify antigens important in immunity and schistosome population genetics. In Brazil, I set up the SOP to obtain single miracidia on FTA cards and transferred the technology. I have been continuously funded my entire career to wor|
Schistosomiasis is a major cause of morbidity in 76 countries of the world where it afflicts more than 260 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.
Most recently I was one of the 4 major contributors that brought the sequence of the schistosome genome to fruition, then resequenced the genome to make it a reference genome, with Tim Anderson developed a 5 cM genetic map for S. mansoni. Using the genetic map, RNAi and biochemical assays, Anderson and I have identified the gene responsible for oxamniquine (OXA) drug resistance, worked out the mode of action of OXA (a first for a drug that treats human helminth infections) and in collaboration with P. John Hart determined the structure of the enzyme (Sulfotransferase)-co-factor and drug. We developed a X-QTL, a method that involves exome sequencing F2 progeny to identify SNPs that co-segregate with a phenotype in this case drug resistance. The research on OXA provides the proof of principal for our approach. We have taken the same genetic approach as with OXA and selected a PZQ resistant strain, performed crosses between PZQ sensitive and resistant schistosomes and identified a quantitative trait locus (QTL) that contains the gene for PZQ drug resistance. We have identified 47 candidate genes and are currently using molecular techniques to identify the one responsible for drug resistance.
The overall focus in the lab is to understand the role genes and gene products play in schistosome-host interactions.
- Structural and Functional Characterization of the Enantiomers of the Antischistosomal Drug Oxamniquine.
Taylor AB, Pica-Mattoccia L, Polcaro CM, Donati E, Cao X, Basso A, Guidi A, Rugel AR, Holloway SP, Anderson TJ, Hart PJ, Cioli D, LoVerde PT
PLoS Negl Trop Dis: 2015-10-01; 9(10); e0004132 Epub: 2015-10-20.
PMID: 26485649   LINK:
- Protective potential of antioxidant enzymes as vaccines for schistosomiasis in a non-human primate model.
Carvalho-Queiroz, C, Nyakundi, R, Ogongo, P, Rikoi, H, Egilmez,NK, Farah, IO, Kariuki, TK, LoVerde, PT.
Frontiers in Immunology: 2015-06-02; 6(); 273 Epub: 2015-06-02.
PMID:   LINK: doi: 10.3389/fimmu.2015.00273.
- Efficient linkage mapping using exome capture and extreme QTL in schistosome parasites.
Chevalier FD, Valentim CL, LoVerde PT, Anderson TJ
BMC Genomics: 2014-07-21; 15(); 617 Epub: 2014-07-21.
PMID: 25048426   LINK:
- Genetic and molecular basis of drug resistance and species-specific drug action in schistosome parasites.
Valentim CL, Cioli D, Chevalier FD, Cao X, Taylor AB, Holloway SP, Pica-Mattoccia L, Guidi A, Basso A, Tsai IJ, Berriman M, Carvalho-Queiroz C, Almeida M, Aguilar H, Frantz DE, Hart PJ, LoVerde PT, Anderson TJ
Science: 2013-12-13; 342(6164); 1385-9 Epub: 2013-11-21.
PMID: 24263136   LINK:
- 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:
Complete Publication Listing