José Gabriel Rinaldi, MD, PhD
Qualifications - Degrees
2011
Doctor of Philosophy (PhD) Molecular and Cell Biology, Program of Development of
Basic Science -PEDECIBA- (PhD Program).School of Science, University of the
Republic, Montevideo, Uruguay. Thesis: “Functional Genomics tools in Helminth
Parasites: Transgenesis and RNAi in trematodes” Director: Dr. Paul J. Brindley, Codirector: Dr. Jose F. Tort (2008-2011)
2008 Master in Science (MSc) Molecular and Cell Biology, Program of Development of Basic
Science-PEDECIBA-School of Science, University of the Republic, Montevideo,
Uruguay. Thesis: “Contribution to Functional Genomics in Fasciola hepatica: RNA
interference”. Dissertation Director: Dr. Jose F. Tort, Co-director: Dra. Estela Castillo
(2005-2008)
2001 Medical Doctor (MD) School of Medicine, University of the Republic (UDELAR).
Montevideo, Uruguay. (1993-2001)
Current appointment. Research Assistant Professor, Department of Immunology, Microbiology
and Tropical Medicine, School of Medicine & Health Sciences, George Washington University.
Washington DC, USA. Since July 2012.
Previous appointments
2003-2013. Research Assistant in Genetics (Gº2, full time permanent position*), Department of
Genetic, School of Medicine, University of the Republic (UDELAR), Uruguay. (*Permanent
positions at the University in Uruguay are obtained by opposition through examination tests in
the discipline, and an evaluation of the candidates´ CVs. The candidates with the higher
cumulative marks are awarded the position).
2008-2012. Post Doc Scientist. Department of Immunology, Microbiology and Tropical
Medicine. The George Washington University, Washington , DC. USA.
1999-2003. Demonstrator in Genetics (Gº1 permanent position), Genetics Department,
School of Medicine, UDELAR. Montevideo, Uruguay
2002-2008. Clinical Assistant, General Medicine Physician. Private Health Institution:
“Asistencial Médica Departamental de Maldonado”, Maldonado, Uruguay.
2002-2004. Fellow of the Education Ministry, Department of Genetic Toxicology and
Chromosome Pathology, Biological Research Institute ‘Clemente Estable’. Montevideo,
Uruguay.
Research Activities
The main interest of our group is the use of Cellular and Molecular Biology approaches to the
study of medical diseases, in particular infectious diseases and neglected tropical diseases that
mainly affect the most impoverished regions of the world. In this regard our work is centered in
the interrelations between parasites and their hosts, seeking for molecular mediators that would
lead to potential targets for drug and/or vaccine development. More recently, I have become
interested in the relationship between infections and cancer, more specifically between helminth
parasites and cancers.
Functional genomics for helminth parasites. My interest in host/parasite interactions is
focused in the development of genetic manipulation approaches and tools to elucidate the
function of genes in order to more readily decipher host parasite relationships and discover new
interventions. My colleagues and I – including Drs. Paul J. Brindley (GWU), Victoria Mann
(GWU), José F. Tort (School of Medicine, Uruguay), and Matthew Berriman (Wellcome Trust
Sanger Institute, England) - have undertaken extensive research during the past decade aimed
at Functional Genomics of trematodes including schistosomes and the liver flukes Fasciola
hepatica and Opisthorchis viverrini. Our group has extensive experience with in vitro culture of
developmental stages of these pathogens, methods and approaches to transduce cultured
schistosomes with retrovirus virions and other integration competent vectors including
transposons, and mouse models of schistosomiasis mansoni and haematobia. I have been
centrally involved in development of molecular tools for transgenesis mediated by retrovirus,
conventional RNAi and vector-based RNAi in S. mansoni. In this regard, I played a key role in
Dr. Paul Brindley’s NIAID sponsored study “Transduction of Schistosoma mansoni by
pseudotyped retrovirus” - award number RO1 AI072773, the aims of which were to develop
replication incompetent Murine Leukemia Virus (MLV) vectors pseudotyped with VSVG for
transduction of development stages of the schistosome and to establish retroviral vector based
RNA interference . During the AI072773 award, we determined that:
1. Retroviral transgenes integrate into schistosome chromosomes;
2. Retroviral vector based RNA interference is functional in schistosomes;
3. Insulator gene sequences incorporated into the retrovirus genome protect transgenes against
silencing;
4. The neoR gene – encoded in retroviral transgenes integrated into schistosome chromosomes
after transduction with pseudotyped retrovirus, facilitated selection of transgenic schistosomules
on the aminoglycoside antibiotic G418;
5. Vertical transmission/ germline transmission of retroviral transgene through the asexual
reproduction cycle in the snail: specifically, eggs transduced with retroviral transgenes hatched,
releasing miracidia which infected snails; cercariae released from these snails were transgenic,
confirming germline transgenesis;
6. Establishment of MLV-transgenic lines of schistosomes for several asexual and sexual
reproduction cycles (i.e. up to 3 generations);
7. Wide scale integration of retroviral viral transgenes throughout the genome of S. mansoni –
including across all seven autosomes and the Z and W sex chromosomes, therefore indicating
the potential utility of this retrovirus for random insertional mutagenesis of S. mansoni.
8. Transfer technology developed in Schistosoma mansoni to the less- well studied flukes
Schistosoma haematobium and Fasciola hepatica. Accordingly we employed transfection
approaches and demonstrated the presence of an active RNAi pathway in S. haematobium and
F. hepatica.
These findings were novel for schistosomes, indeed novel for any parasitic worm. These
findings and reviews on genetic manipulation of schistosomes have been published in highly
ranked journals including The FASEB Journal, PLoS Neglected Tropical Diseases, Transgenic
Research, International Journal for Parasitology and PLoS Pathogens.
Collaborations:

Dr. Matthew Berriman. Wellcome Trust Sanger Institute, Cambridge, England
http://www.sanger.ac.uk/research/faculty/mberriman/

Dr.Sutas Suttiprapa. Department of Microbiology, Faculty of Science, Mahidol University,
Bangkok, Thailand http://www.sc.mahidol.ac.th/scmi/index.htm

Dr. José F. Tort. Department of Genetic, School of Medicine, University of the Republic,
Uruguay http://www.genetica.fmed.edu.uy

Dr. Carlos Carmona. Institute of Hygiene, School of Science, University of the Republic,
Uruguay http://www.higiene.edu.uy/

Dr. Martín Cancela. Center for Biotechnology (CBiot) of the Federal University of Rio
Grande do Sul (UFRGS), Brazil http://www.cbiot.ufrgs.br/cenbiot/cenbiot-ing/index.html

Dr. Pablo Smircich. Laboratory of Molecular Interactions, School of Science, University of
the Republic, Uruguay http://www.fcien.edu.uy/
Infectious-related cancers. Our group is interested in the relationship between infections and
cancer, more specifically between helminth parasites and cancers. Colleagues, including Drs.
Paul J. Brindley, Jeffrey M. Bethony (Microbiology, Immunology, and Tropical Medicine George
Washington University, School of Medicine & Health Science, GWU )and Jason P. Mulvenna
and I are developing model systems to investigate the role of Schistosoma haematobium in
squamous cell carcinoma of the bladder and Opisthorchis viverrini in bile duct cancer. The
research is not only focused on the basic biology of the carcinogenesis mediated by the
parasites, but also on the survey for potential diagnostic and prognostic cancer biomarkers such
as miRNAs. In addition, we have also started the screening for miRNA signatures as potential
biomarkers in the Epstein-Barr virus-related nasopharyngeal carcinoma.
-
Opisthorchis viverrini and cholangiocarcinoma (CCA).
Liver fluke infection caused by Opisthorchis viverrini is a major public health problem in Thailand
and adjacent countries. In addition to infection-associated morbidity, infection with O. viverrini
and the related Clonorchis sinensis are unarguable risk factors for cholangiocarcinoma. Our
group studies the basic biology of the host-parasite interaction focus on proteins and/or other
molecular mediators derived from the liver fluke and involved in the events that would eventually
lead to carcinogenesis. In addition, we have started to screen miRNA profiles in human samples
that would be employed as biomarkers in the future.
Collaborations:

Dr. Banchob Sripa. Department of Pathology, Faculty of Medicine, Khon Kaen University,
Khon Kaen, Thailand http://www.md.kku.ac.th/en/index.php

Dr. Jason P. Mulvenna. Infectious Disease and Cancer, Queensland Institute for Medical
Research, Brisbane, Australia. http://www.qimr.edu.au/

Drs. Alex Loukas and Michael Smout. Centre for Biodiscovery and Molecular Development
of Therapeutics, Queensland Tropical Health Alliance, James Cook University. Australia
https://research.jcu.edu.au/research/bmdt/our-research
-
Schistosoma haematobium and squamous cell carcinoma of the bladder (SCC)
Schistosomiasis haematobia is a major Neglected Tropical Disease (NTD) caused by infection
with a water-borne parasite, a blood fluke termed Schistosoma haematobium. There are well
known causative associations between this NTD and bladder cancer (squamous cell carcinoma
of the bladder) and interactions between this infection and the human endocrine (hormonal)
system. We investigate why this parasite causes bladder cancer, focusing on hormone like
molecules, such as catechol-estrogens that the parasite release into the bladder of infected
persons.
Collaborations:

Dr. José Manuel Correia da Costa. Center for the Study of Animal Science, ICETA,
University of Porto, Portugal. CIBP – Centre for Parasite Immunology and Biology, National
Institute of Health, Porto, Portugal

Dr. Mónica Botelho. Center for the Study of Animal Science, ICETA, University of Porto,
Portugal. CIBP – Centre for Parasite Immunology and Biology, National Institute of Health,
Porto, Portugal

Dr. Nuno Viale. CIQUP, Chemistry and Biochemistry Department, Faculty of Sciences,
University of Porto, Portugal

Dr. Júlio Santos. Clínica da Sagrada Esperança, Luanda, Angola. http://www.cse-ao.com/

Dr. Michael H. Hsieh. Department of Urology, Stanford University School of Medicine.
http://uti.stanford.edu/
-
Epstein-Barr virus (EBV) and Nasopharyngeal carcinoma (NPC)
The etiology of NPC is complex, involving multiple factors, including EBV, which appears to play
an oncogenic role. Up to 40% percent of NPC cases present at an advanced stage, likely due to
the deep location of the tumor in the lymphatic-rich nasopharynx and the tumors propensity for
early lymphatic spread. Accordingly, new biomarkers for the prognosis and guidance of early
chemotherapy are desperately needed for NPC. The expression profile of microRNAs (miRNAs)
in a particular cell and/or tissue (i.e. the miRNAome) has the potential to distinguish normal from
malignant states and hence can be employed as biomarkers for cancer diagnosis and
prognosis. Drs. Jeffrey M Bethony, Jason P. Mulvenna and I are currently working on the
assembly of a signature of dysregulated miRNAs associated with NPC tissue by highthroughput sequence analysis of small RNAs.
Collaborations:

Dr. Jeffrey M. Bethony. Microbiology, Immunology, and Tropical Medicine George
Washington University, School of Medicine and health Science, GWU.
http://smhs.gwu.edu/microbiology/

Dr. Jason P. Mulvenna. Infectious Disease and Cancer, Queensland Institute for Medical
Research, Brisbane, Australia. http://www.qimr.edu.au/

Dr. Paul Levine. Department of Biochemistry, School of Medicine and Health Science,
George Washington University. http://smhs.gwu.edu/biochemistry/

Dr. Samantha Easly. Department of Pathology, School of Medicine and Health Science,
George Washington University. http://smhs.gwu.edu/pathology/

Dr. Nader Sadeghi. Medical Faculty Associates, The George Washington University,
Washington.
Selected publications
1. Nuno Vale, Maria João Gouveia, Mónica Botelho, Banchob Sripa, Sutas Suttiprapa, Gabriel
Rinaldi, Paula Gomes, Paul J. Brindley and José Manuel Correia da Costa (2013) LC-
MS/MS survey of oxysterols in Opisthorchis viverrini. Parasitology International 62 (2013)
535–542
2. Botelho MC, Vale N, Gouveiac MJ, Rinaldi G, Santose J, Santosf LL, Gomes P, Brindley
PJ, Correia da Costa JM (2013). Induction of tumour-like phenotypes in urothelial cells
exposed to Schistosoma haematobium soluble egg antigens possibly through estrogen-DNA
adducts mediated pathway. International Journal for Parasitology 43(1): 17-26.
3. Rinaldi G*, Eckert SE*, Tsai IJ*, Suttiprapa S, Kines KJ, Tort JF, Mann VH, Turner DJ,
Berriman M**, Brindley PJ** (2012) Germline transgenesis and insertional mutagenesis in
Schistosoma mansoni mediated by murine leukemia virus. PLoS Pathogens 2012
Jul;8(7):e1002820. Epub 2012 Jul 26. (* These authors contributed equally to this work) (**
corresponding authors)
4. Rinaldi G, Suttiprapa S, Tort JF, Folley AE, Skinner DE, Brinldey PJ (2012) An antibiotic
selection marker for schistosome transgenesis. International Journal for Parasitology. 2012
Jan;42(1):123-30
5. Young ND*, Jex AR*, Li B*, Liu S, Yang L, Xiong Z, Li Y, Cantacessi C, Hall RS, Xu X, Chen
F, Wu X, Zerlotini A, Oliveira G, Hofmann A, Zhang G, Fang X, Kang Y, Campbell BE,
Loukas A, Ranganathan S, Rollinson D, Rinaldi G, Brindley PJ, Yang H, Wang J**, Wang
J**, Gasser RB** (2012) Whole-genome sequence of Schistosoma haematobium. Nature
Genetics 2012 Jan 15. doi: 10.1038/ng.1065 (* These authors contributed equally to this
work) (** corresponding authors)
6. Suttiprapa S*, Rinaldi G*, Brindley PJ (2011) Prototypic chromatin insulator cHS4 protects
retroviral transgene from silencing in Schistosoma mansoni. Transgenic Research
doi:10.1371/journal.pntd.0000593 (* These authors contributed equally to this work)
7. Duvoisin R*, Ayuk MA*, Rinaldi G, Suttiprapa S, Mann VH, Lee CM, Harris N, Brindley PJ
(2011) Human U6 promoter drives stronger shRNA activity than its schistosome orthologue
in Schistosoma mansoni and human fibrosarcoma cells. Transgenic Research doi:
10.1007/s11248-011-9548-0 (* These authors contributed equally to this work)
8. Rinaldi G, Okatcha TI, Popratiloff A, Ayuk MA, Suttiprapa S, Mann VH, Liang Y, Lewis FA,
Loukas A, Brindley PJ (2011) Genetic manipulation of Schistosoma haematobium, the
neglected schistosome. PLoS Neglected Tropical Diseases 5(10): e1348.
9. Cancela M, Ruetalo N, DellOca N, Da Silva E, Smircich P, Rinaldi G, Roche L,
Carmona C, Alvarez-Valin F, Zaha A, Tort JF (2010) Survey of transcripts expressed by
the invasive juvenile stage of the liver fluke Fasciola hepatica. BMC Genomics, v. 11:227
10. Rinaldi G, Morales ME, Alrefaei YN, Cancela M, Castillo E, Dalton JP, Tort JF, Brindley
PJ (2009) RNA interference targeting leucine aminopeptidase blocks hatching of
Schistosoma mansoni eggs. Molecular and Biochemical Parasitology, v. 167 , p. 118-126
11. Rinaldi G, Morales ME, Cancela M, Castillo E, Brindley PJ, Tort JF (2008) Development of
functional genomics tools in trematodes: RNA interference and luciferase reporter gene
activity in Fasciola hepatica. PLoS Neglected Tropical Diseases, v. 2 7 , p. e260-10
12. Cancela M, Acosta D, Rinaldi G, Silva E, Durán R, Roche L, Zaha A, Carmona C, Tort,
JF (2008) A distinctive repertoire of cathepsins is expressed by juvenile invasive Fasciola
hepatica. Biochimie, v. 90 10 , p. 1461-1475
Mentoring activities in the laboratory
As co-investigator in the projects mentioned above I have served as collaborator in training and
assisting researchers and graduate, master and doctoral students in both the Department of
Genetics, School of Medicine, UDELAR, Uruguay and in the laboratory of Paul Brindley,
Department of Microbiology, Immunology and Tropical Medicine, GWU.
Students for whom I served as collaborator and advisor:

Dr. Hongbin Yan (PhD). Lanzhou Veterinary Research Institute, Chinese Academy of
Agricultural Science. One year internship at GWU. Project: Developing functional genomic
tools for parasitic helminthes. 2013-2014

Pitchaya Matchimakul, DVM. Ph.D. Candidate in Biomedical Sciences, Faculty of Graduate
School, Khon Kaen University, Khonkaen, Thailand. Thesis title: Opisthorchis viverriniThioredoxin-1 interaction with human apoptosis signal regulating kinase-1 (ASK-1) related
anti-apoptosis mechanism in cholangiocytes. Internship at GWU 2013.

MPh Anne E. Folley. Master in Public Health Microbiology & Emerging Infectious Disease
Program. The George Washington University. Preceptors: Drs. Gabriel Rinaldi and Paul J.
Brindley. Final Project: Development of Antibiotic Selection to Facilitate Retroviral Based
Transgenesis in schistosomules and eggs of Schistosoma mansoni. 17 May 2013

Dr. Nicolás Dell’Oca (MD). Master in Science Student (MSc) Molecular and Cell Biology,
Program of Development of Basic Science-PEDECIBA-School of Science, University of the
Republic, Montevideo, Uruguay. Final Project: “Functional Genomics for the liver fluke
Fasciola hepatica”. Mentor: Dr. Jose F. Tort. An internship was coordinated and Nicolás
spent two months (April- June 2012) in the laboratory of Paul J. Brindle

BS. Danielle Skinner. PhD Student. Final Project:“ Functional studies with Schistosoma
mansoni vasa-like gene(s)” The George Washington University, Washington DC (2013).
Mentor: Dr. Paul J. Brinldey

MS. Ana Zeraik. PhD Student. Final Project: “Caracterização Biofísica e Estudos Funcionais
das Septinas de Schistosoma mansoni” Programa de Pos-Graduacao do Instituto de Fisica
de Sao Carlos (IFSC), da Universidade de Sao Paulo, na area de fisica aplicada, opcao
biomolecular. Instituto de Fisica de Sao Carlos, Grupo de Biofisica molecular Sergio
Mascarenhas.(2013) Mentor: Prof. Dr. Ricardo De Marco. Co-mentor: Prof. Dr. Ana Paula
Ulian de Araujo

Dr. Tunika I. Okatcha (PhD). PhD Final Project: “Vertical transmission, longevity, and
expression of piggyBac transgenes in the human blood fluke, Schistosoma mansoni”. 2011,
Tulane University, New Orleans, LA, USA. Mentor Dr. Paul J. Brindley

Dr. Yousef N. Alrefaei (PhD). PhD Final Project: “Mos1 mariner transposon based
transgenesis of the human blood fluke, Schistosoma mansoni”. 2011, The George
Washington University, Washington DC. Tutor Dr. Paul J. Brindley

MS Raphaël Duvoisin. MS Final Project: ‘Development of vector based RNA interference in
Schistosoma mansoni’. Master of Science (MSc) in Life Sciences and Technologies, Ecole
Polytechnique Fédérale de Lausanne. 2010-2011. Mentor: Nicola Harris, Co-mentor: Paul J.
Brindley

Dr. Mary A. Ayuk (PhD). PhD Final Project “New approaches to gene knockdown in
Schistosoma mansoni targeting the hemoglobin proteolysis cascade”. 2011, Howard
University, Washington, DC. Mentor: Dr. Clarence M. Lee (tutor), co-mentor: Dr. Paul J.
Brindley

Dr. Kristine Kines (PhD). PhD Final Project “Retroviral mediated transgenesis of the human
blood fluke, Schistosoma mansoni”. 2009, Tulane University, New Orleans, LA, USA.
Mentor: Dr. Paul J. Brindley

Dr. María E. Morales (PhD). PhD Final Project “Transposon mediated transgenesis of
schistosomes”. 2007, Tulane University, New Orleans, LA, USA. Mentor: Dr. Paul J.
Brindley
Teaching Activities
School of Medicine & Health Sciences, George Washington University, USA
Postgraduate teaching
Lecture “Schistosomiasis”. Tropical Infectious Diseases (TID, Micro 6292). Spring Semester of
2012, 2013. Dr. Jeffrey M Bethony. Microbiology, Immunology, and Tropical Medicine. School of
Medicine and health Science. George Washington University.
Structuring, planning and organization of the semester Course Translational Molecular
Biomedicine. Organizer of the course syllabus and Instructor (2013). The course will be part of
the curriculum of the Proposed New Professional Science Masters Program. M.S. in Clinical
and Translational Microbiology. Dept. of Microbiology, Immunology & Tropical Medicine. Health
Sciences Programs
School of Medicine, University of the Republic, Uruguay
Undergraduate teaching
Lectures in the Cell Biology Courses, 1st year of Medical Doctor and Medical Technologists
curricula. Themes included: Basic genetic mechanisms, Molecular genetics, Genomics, Gene
regulation.
Teaching in the Genetics module of the Basic Introductory course in the Medical School.
Themes included: Molecular Basis of Genetics, Classic Genetics and Human Genetics.
Demonstrator in practical classes during the courses Cell Biology, Tissue Biology, Reproduction
and Development, of the School of Medicine.
Postgraduate teaching
Teaching in Program of Development of Basic Science (PEDECIBA) and Program of
Biomedical Investigation (PROINBIO) postgraduate courses:

Molecular Genetics and Medicine (every two years) Subject: Genomic Imprinting,
Regulatory non-coding RNAs.

“Transgenesis and RNAi in flatworms”. Postgraduate course: Advances in the Molecular
Biology and control of helminth parasites. Dra. Mara Rosenzvit. Universidad de Buenos
Aires - Facultad de Medicina - Departamento de Microbiología, Parasitología e Inmunología.
Buenos Aires, Argentina. October, 2011.

“RNAi in flatworms”. Workshop of Functional Genomics for helminth parasites. Dr. José F.
Tort. Departamento de Genética, Facultad de Medicina. Montevideo, Uruguay. November,
2011
Teaching in postgraduate courses of PEDECIBA (Program of Development of Basic Science) :

“Post transcriptional regulation of gene expression in eukaryotes”. Laboratorio de
Interacciones Moleculares. Dra. Beatriz Garat, and Dr. Jose Tort. School of Science,
Montevideo, Uruguay. May 2008.

“Parasite Biology: immunologic, biochemical and molecular basis of the Parasitism”.
Lecture: “Functional Genomic tools in helminthes parasites”. Unidad de Biologia Parasitaria,
Instituto de Higiene, School of Science. Dr. Carlos Carmona. 2007

In Situ Hybridization Techniques in Parasite Research (2006), Lecture: Interference by
double stranded RNA in helmiths.

Amsud-Pasteur and PEDECIBA regional postgraduate course: "Small RNAs: New
Mechanisms in gene expression regulation and tools for reverse genetics", Dra Beatriz
Garat, and Dr. Bruno Dallagiovanna School of Science, Montevideo, Uruguay. December
2006.