The National Cancer Institute (NCI) under the scope of the NIH has recently announced the granting of a funding program for the international consortium formed by Argentine and USA researchers to study human cancer subjects related to Acquired Immune Deficiency Syndrome (AIDS).
The consortium is formed by researchers of one institution from the USA and four from Argentina. These nodes are at the University of Miami, Instituto de Biología y Medicina Experimental (IBYME, CONICET-FIBYME), the Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE, CONICET-UBA) at the Universidad Nacional de La Plata and at the Fundación Huésped.
When the Human Immunodeficiency Virus (HIV) infects people, it weakens their immune system. This turns them more vulnerable to different infections and the development of malignant tumors linked to diverse carcinogenic viruses.
“This project is a real international collaboration platform for research and human resources training focused on the study of this type of tumors in Argentina, which have neglected and have high prevalence in infected individuals, and therefore great social impact”, Enrique Mesri explains. He leads the node formed by the Center for AIDS Research (Miami CFAR) and the Sylvester Comprehensive Cancer Center of the University of Miami, in which Julián Naipauer also participates.
This consortium has one unique aspect: the main goal is to train a critical mass of young researchers. Mesri comments that “in addition to the funds devoted to the studies, the researchers have access to tutorials with different senior professionals, courses and collaborations to start their own research.”
The population under study
The samples that are going to be tested come from the Fundación Huésped. They consist of 300 HIV positive and HIV negative individuals at risk of infection by oncogenic viruses such as the human papillomavirus (HPV) and the human herpes virus type 8 (HHV-8), like in the case of men who have sex with men and transgender women.
“The project aims at studying -from a biological, medical an epidemiological point of view- two cancer-causing viruses.: the HPV and the herpes virus associated to the Kaposi’s sarcoma (KSHV) or HHV-8 and the cancers related to them, especially anal cancer (linked to HPV) and the Kaposi’s sarcoma (linked to KSHV)”, Pedro Cahn, director of the Fundación Huésped, describes.
Cahn comments that the study is going to focus on two populations, “men who have sex with men and transgender women, who are the populations of Argentina with the highest risks of acquiring HIV/AIDS and the most affected by these pathologies.”
In our country, the population of men who have sex with men has one incidence of HIV infection between 12 and 15 per cent, while this figure rises to 34 per cent in transgender women. For Cahn, these groups also coincide with the ones that are at higher risk of infection by the viruses that are going to be studied in this project, which are linked to the risk of developing Kaposi’s sarcoma and anogenital cancers.
The study comprises two sample sources: a cohort of 300 individuals at risk to study the dynamic of the oncogenic virus’s infection and one repository of 450 tumor samples from people with HIV that come from a network of public and private hospitals of Buenos Aires, coordinated by the Fundación Huésped.
For Gabriel Rabinovich, CONICET senior researcher and member of the IBYME node, the consortium seeks to address –from an interdisciplinary approach– a problem that has clinical, biological and social implications.
“At a clinical level, the scientists are going to look for new therapeutic targets and biomarkers in those patients that have tumors associated to AIDS. In the case of the biological level, the experts plan to generate database and biological material linked to those tumors so as to obtain key information for their treatment. We are also talking about socially vulnerable groups and it is a huge challenge to provide solutions for them. Besides, it’s a great honor to be part of this team and an exciting challenge to use the tools provided by immuno-oncology to sucessfully treat this patients”, the researcher affirms.
A major strength of this international consortium is the complementary scientific expertise of each group; which, as in a puzzle, perfectly assembles as a whole bigger than the sum of its components
At the Centro de Investigaciones Inmunológicas Básicas y Aplicadas (CINIBA) of the Universidad Nacional de La Plata (UNLP), Martín Abba, who is an CONICET independent researcher, leads a team in which Ezequiel Lacunza, associate researcher, and María Virginia Ponzinibbio, associate professional, working on bioinformatics applied to oncogenomics, a set of high-throughput computational techniques geared to identify mutations and alterations in gene expression driving tumorigenesis
“All the samples that demand genomic analysis are going to be first processed in La Plata, and then they are going to be sequenced at the University of Miami. Subsequently, the information will be stored and completely analyzed in our institution, so it could be easily distributed among the member of the consortium, thus facilitating the centralization of the information and the collaborations among the different consortium components ”, Abba explains.
In this way, in each of the tumors and experimental models, scientists will be able to determine which mutations each has and how the gene expression changes. Thus, researchers will have the chance to identify new potential biomarkers that indicate how the disease advances, and identify new therapeutic targets.
At the IFIBYNE, Omar Coso, CONICET independent researcher, and Ana Raimondi, associate researcher, are going to study specifically which genes are expressed in these tumors under different conditions. This will allow experts to know how the intercellular communication circuitry works.
“These circuits are deregulated in pathologies such as cancer. Within this project, we study how the circuits are altered in cells that express genes linked to viral cancers, which are favored in immunosupression conditions, like in the case of those affected by AIDS”, Coso comments.
The IBYME node consists of Gabriel Rabinovich, CONICET Superior researcher, and Diego Croci and Juan Pablo Cerliani, associate researchers. “Our objectives are to study how those viruses evade the immune system to form tumors in those patients, and to assess the role of the galectins –therapeutic targets that we analyze at the laboratory– for potential treatments”, Cerliani states.
For more than 25 years, the Fundación Huésped works on clinical research and the development of projects and studies on HIV/ AIDS. Within this consortium, the foundation is going to participate as a research center and as link among the oncological hospitals and the basic research institutions. This node consists of Pedro Cahn; Huesped Director, Valeria Fink and Omar Sued, scientific director at the foundation.
“We also want to organize a sample repository that allows us to conduct studies that help to better understand the biology of those virus and tumors. The aim is to provide information for new possible therapies”, Cahn explains.
This project establishes interdisciplinary collaboration between groups that excel at their disciplines and will allow addressing a health issue prevalent in a vulnerable sector of the population.
“The greatest strength of this project is that it comprises different groups with diverse studies that range from the molecular aspects of HIV infection, various types of cancer associated to AIDS, to more clinical aspects”, Rabinovich comments. And Abba concludes: “The joint effort makes a great difference and the data and samples that we will generate will be in constant traffic from one Lab to the other, greatly contributing to our common success”
|The training program: one of the keys |
“This consortium is supported by three pilars”, Cerliani affirms, “molecular and clinical research, the creation of one repository of tumor samples linked to viral infections, and the training and support to young researchers”. Cerliani is one of the seven professionals trainees together with Ana Raimondi, Ezequiel Lacunza, Diego Croci, Julián Naipauer, María Virginia Ponzinibbio and Valeria Fink.
The project provides support to scientists who are in the first stages of their research and allows them to create a network of relationships with foreign universities and establish collaborations. Furthermore, they will be able to have training at the Center for AIDS Research and at the Sylvester Comprehensive Cancer Center of the University of Miami, and in different institutes of Argentina.
“They will have the possibility of exchanging the resources between local laboratories and foreign collaborators”, Coso adds, and comments: “And this, in addition to the creation of one repository of samples of DNA, RNA, proteins and infected patients’ tissues will enable experts to efficiently translate the molecular research results to the design of procedures of prevention, diagnosis and to the possible treatment of patients”.