Translation and Application Core

Leader: Joshua Lang, MD – jmlang@medicine.wisc.edu

Translational Biomarkers

Minimally invasive liquid biopsies have revolutionized biomedical research. Using small amounts of biospecimens (blood, plasma, urine), the biology of health and disease can be tracked effectively longitudinally in short (minutes) or expanded (years) time frames and in large numbers of subjects. The platform will facilitate in-depth translational and reverse translational studies. For example, a biological age index derived from laboratory animal studies can be adopted for use in more translational models (nonhuman primates) or in humans. Biomarkers derived from clinical studies can be reverse translated for use in mechanistic studies, using models that allow for more controlled study design, include genetic malleability, ease of pharmacological application, and have shorter lifespans.

The Liquid Biopsy platform takes advantage of a microfluidic engineering concept that was developed into a microscale technology. Modalities include exploratory (biologic plausibility but performance characteristics and reproducibility not established), and integrated (analytically validated biomarkers), with options to generate integral biomarkers (CLIA-certified biomarkers). Standard analytes purified range from plasma for cytokines, metabolites, and exosomes as well as nucleated cells for immune cell studies. The analyses also include cell phenotyping, gene expression profiling, and genetic analysis among others. The Liquid Biopsy Platform leverages considerable investment in infrastructure as part of the UWCCC Circulating Blood Biomarkers Core and validated assay development within the WNPRC Assay Services laboratories.

Leader: Ricki Colman, PhD – rcolman@primate.wisc.edu

Aging in nonhuman primates (NHP)

The NHP Pipeline facilitates translation of insights gained from biology of aging studies as the next step along the translational pathway, providing access to NHP biobanks in addition to supporting potential prospective studies.  NHPs are the phylogenetically closest relatives of humans sharing ~93% sequence identity with the human genome and provide physiologically important and clinically relevant models for the evaluation of the biology of aging and age-related diseases. The rhesus macaque (Macaca mulatta and Macaca fascicularis) is a well-characterized aging model with a lifespan measured in decades. They develop and age similarly to humans, and display patterns of eating and sleeping that mirror those of humans. The common marmoset (Callithrix jacchus) has a relatively short lifespan, high fertility, rapid development, small size and human-like social structure.

Curated and facilitated access to WNPRC will provide the resources and wide-ranging expertise in nonhuman primate biomedical research needed to guide investigators along the translational pathway. The NHP pipeline will provide access to extensive electronic health records system, including colony management, health, pathology and experimental data for all animals that ever lived at the WNPRC. The NHP team will work with WiNSC investigators to optimize experimental design (species, age, feasibility) and facilitate access to tissues and associated metadata that generally includes lifelong records of all clinical, behavioral and experimental experiences. Importantly, funding for aging focused pilot studies using NHP is offered through an annual competition and supported by a joint WiNSC/WNPRC initiative.

Translation to humans

Human subject de-identified data and biospecimens from cross-sectional studies are available through the Translational Science BioCore Biobank. UW-Madison is home to repositories of data and biospecimens from over 32,000 participants including NIH and UW funded ongoing longitudinal human aging studies.

The Translational Science BioCore (TSB) Biobank is part of the UW Carbone Cancer Center and human tissues, blood and other biospecimens that are prospectively collected, processed, and stored for distribution to investigators to promote basic, translational, and clinical research. The Biobank contains samples from nearly 7,000 unique donors, representing a broad array of age-associated disease, often with matched normal controls, tissue microarrays from multiple cancer types, and blood from healthy volunteers.