Translational Science Initiative (TSI)

Lead PI: Carlos A. Sariol
Zika initiative at CPRC
There are four distinct DENV serotypes, DENV-1 through 4, all of which cause a spectrum of illnesses ranging from classic dengue fever to severe, potentially fatal disease characterized by hemorrhage and systemic shock. Infection with one serotype (primary infection) leads to durable life-long immunity against the infecting serotype. However, immunity to a single DENV serotype predisposes an individual to severe disease upon infection by a different serotype (secondary infection). Since its introduction in the Americas region, ZIKV has been associated with severe birth defects. One question that remains open is the role of previous dengue or any other flavivirus immunity in ZIKV pathogenesis, as is the case for subsequent DENV infections. Our group has provided answers to some key questions on this issue (1-4).
The results of this study, obtained with the support  of the P40 OD012217, allowed our team to apply and receive a five-year grant from the R01AI148264-01 (NIAID) entitled "Dengue-Zika: Correlates of Cross-Protection in Non-Human Primates." Dr. Carlos Sariol, Director of the Department of Comparative Medicine, serves as the Principal Investigator of this project.  
Recent publications:
  1. Pantoja P, Perez-Guzman EX, Rodriguez IV, White LJ, Gonzalez O, Serrano C, et al. Zika virus pathogenesis in rhesus macaques is unaffected by pre-existing immunity to dengue virus. Nature communications. 2017;8:15674.
  2. Perez-Guzman EX, Pantoja P, Serrano-Collazo C, Hassert MA, Ortiz-Rosa A, Rodriguez IV, et al. Time elapsed between Zika and dengue virus infections affects antibody and T cell responses. Nature communications. 2019;10(1):4316.
  3. Sariol CA, Nogueira ML, Vasilakis N. A Tale of Two Viruses: Does Heterologous Flavivirus Immunity Enhance Zika Disease? Trends Microbiol. 2018;26(3):186-90.
  4. Serrano-Collazo C, Pérez-Guzmán EX, Pantoja P, Hassert MA, Rodríguez IV, Giavedoni L, et al. Effective control of early Zika virus replication by Dengue immunity is associated to the length of time between the 2 infections but not mediated by antibodies. PLoS neglected tropical diseases. 2020;14(5):e0008285.

Development of rhesus monkeys as a model of pre-diabetes
Dr. Sylvette Ayala, UPR-MSC

Like humans, rhesus monkeys develop spontaneous pre-diabetes followed by the overt condition during middle age. Rhesus monkeys comprise an accurate model for translational research to study the impact of pharmacological interventions on metabolic, molecular, and tissue pathological changes preceding IR/T2D. This project will take advantage of that to develop: 1) new models of pre-diabetes as powerful research tools available to the entire scientific community; and 2) new strategies for designing and testing novel interventions to prevent and treat metabolic diseases.


Insights into Age-Related Ocular Disease by Uniting Clinical Assessment and 'Omics in a Naturally Occurring Model

figure 1The goal of our project is to understand genetic and metabolic differences in ocular tissues of individuals with and without naturally occurring age-related diseases, (e.g. open-angle glaucoma (OAG), ocular hypertension (OHT)) to improve our understanding of the causes and consequences of these diseases. Our first aim is to diagnose the frequency of OAG and OHT in the study population and to track progression longitudinally. We are using a comprehensive, multiplatform approach that combines the latest imaging technologies with traditional ocular exams. Our second aim is to identify gene expression and metabolite profiles associated with ocular diseases. We are conducting a transcriptomic (RNA-sequencing) and metabolomic study of glaucoma-relevant ocular tissues from a subset of individuals with OAG/OHT and from closely related individuals with health visual systems. For genes and metabolites associated with disease, we will examine the linked biological pathways relevant for cell death and inflammation; pathways implicated in human glaucoma, a leading cause of blindness globally. We unite ocular phenotypes with the transcriptomics and metabolomics of affected ocular tissues originating from the same samples. Our research will provide new foundational knowledge concerning the biology and pathophysiology of glaucoma, essential data for understanding this diverse and multifaceted disease. With this information, we will create databases of detailed images and associate 'omics data for normal and diseased retinas. This information will help us to improve early diagnostic tools, and identify druggable targets for disease treatments.   

Key Collaborators   
Amanda Melin     
James Higham      

Assessing the anti-inflammatory role of Fasciola hepatica fatty acid binding protein in a non-human primate septic shock model

Dr. Ana Espino, UPR-MSC

The present seeks to validate a molecule of parasitic origin termed Fh12 as a drug to prevent and treat septic shock. There are about 200,000 deaths caused by sepsis in the US each year. These deaths are primarily due to the persistence of a hyper activation of phagocytes that continuously secrete a storm of inflammatory cytokines, which result in hemorrhage, respiratory collapse and multi-organ failure. Although effective use of antibiotics has resulted in improved prognosis in many cases of sepsis, neutralization of inflammation is considered essential for preventing severe consequences of sepsis. A large number of bacterial products are responsible for the hyper activation of the phagocytes via TLRs-interaction. The development of antagonists that block either activation through TLRs or inhibit the storm of inflammatory molecules has become a priority in the search for novel anti-inflammatory drugs. We have strong preliminary data demonstrating that a single dose of 15μg of a 12kDa F. hepatica fatty acid binding protein (Fh12) is enough to prevent the inflammatory response induced by LPS-endotoxin in a mouse model of septic shock. The current project has two main focuses. First, to develop a non-human primate controlled septic shock model to study the change pattern of inflammatory cytokines during the early phase of septic shock, and second, to demonstrate that a single intravenous injection with Fh12 will prevent the inflammatory response induced by bacterial infection and will neutralize the inflammatory response after the onset of septic shock.


Luis Acevedo-Marquez, MSc studentSource-tracking oral and anogenital microbiomes and alpha papillomavirus (PV) infections in rhesus macaques (Macaca mulatta)

Luis Acevedo-Marquez, MSc student
UPR Medical Sciences Campus, Dept. Microbiology and Medical Zoology

PI. Dr. Filipa Godoy-Vitorino,

Mammals evolved by acquiring a maternal microbiome from the birth canal, by which the first microbiota prime the immune system and the whole system physiology. The past decade has been remarkable in revealing the fundamental role of the microbiome (microbial communities) in health and diseases. Our group has been studying anogenital microbiomes in the context of Human Papilloma Virus infectious and found specific biomarkers associated to the disease.

To explore the transmission of oral and anogenital microbiomes with hosts, it is necessary to have data describing host-microbe dynamics in non-human species with variations in disease prevalence and host sexual behavior. Rhesus macaques are useful models for studying human reproduction-related microbiomes, due to the similar physiology and anatomy, and their promiscuous sexual behavior. Being close phylogenetic relatives, the study of the transmission of microbiomes and PV infections in these animals provides an excellent comparative model for humans.

This MSc thesis aims to: 1) Characterize the oral, anal, vaginal and penile bacterial biomes in female and male rhesus macaques; 2) Determine diversity of naturally occurring oral and genital alpha Papillomaviruses (PVs) among male and female macaques; and 3) Define the correlation between the PV–infected animals and their microbial communities.

This pioneer work will offer a clear understanding of the host-microbiome dynamics of the oral, anogenital microbiome routes in these non-human primates, which will be pertinent to understand sexually-transmitted microbes and PV in humans.