DNA-N

Translational Medicine

The development and promotion of fundamental research discoveries for practical applications and commercial development to treat disease.

The translational research program (TRP) is a cornerstone of CBMR´s effort to use basic research knowledge for practical applications to improve patient health. The TRP is composed of a wide variety of scientific and technological expertise in biomedical and bioengineering sciences that bridge the gap between basic science and clinical applications, the development of new technologies and products for commercialization and industrial development. A primary focus of the TRP is the discovery and repurposing of therapeutic drug candidates to treat disease. This focus extends to include the development of biomarkers, biosensors and drug delivery systems to improve patient treatment.

The TRP expertise and collaborative drug discovery partnership allows us to continue compound screening efforts for a broad range of diseases examining crucial molecular targets. These targets include the nuclear export receptor CRM1, tumor suppressors (FOXO and p53), oncogenic TRIB2, the plasminogen receptor annexin A2 heterotetramer (involved in cancer cell invasion/metastasis), beta-glucocerebrosidase (mutated in Gaucher’s disease) and infectious prion protein (PrSC) using complex chemical compound libraries, natural products and approved drug molecules (for drug repurposing).

The TRP is investigating effective ways to prevent and diagnose diseases with particular emphasis directed towards cancer, including breast, ovarian, colon, pancreatic and skin cancer. Furthermore the TRP is driving the development of personalized medicine and in particular, the identification of biomarkers (the first step in this process).

The TRP is actively identifying, validating and developing disease and drug related biomarkers to enhance individual patient disease prediction as well as patient management for a range of cancers that currently present with poor patient prognosis. Included within this line of investigation, the TRP is using newly identified biomarkers to predict chemotherapeutic resistance to current, as well as a novel anti-cancer drugs.

The TRP is also actively exploring new methods to administer biomolecules and pharmaceutical compounds to achieve increase their therapeutic effect. This includes unique technologies based on virus like particles for the targeted delivery of therapeutics to specific cells or tissues. In addition the TRP is continuing to develop polymeric drug delivery systems, both at nano and micro scale to encapsulate therapeutic agents (e.g., antibiotics for the treatment of tuberculosis).

TRP Main Research Lines

Pre-clinical development of lead molecules /compounds with pharmaceutical companies

The TRP is conducting compound screening efforts to identify small molecules that potently inhibit the nuclear export machinery. We are investigating the efficacy of these novel nuclear export inhibitors in a broad range of cancer cell line and xenograft models to evaluate their anti-cancer and pharmacokinetic properties.

Discovery and repurposing of therapeutic drug candidates

Based on collaborative partnerships and previously established assay technology the TRP is conducting drug discovery campaigns identifying lead compounds capable of assisting intracellular glucocerebroside protein folding to treat Gaucher disease, excluding FOXO factors from the cell nucleus (ablating chemotherapy resistance in a range of cancers), extending life span of C. elegans and depleting the mutated prion protein from the cell membrane. Specifically the CBMR´s drug discovery effort is the continued development of lead compounds to treat several diseases including lipid storage diseases, neurodegenerative diseases and cancer.

Novel Biomedical Instrumentation

The new technique of Quartz Crystal Microbalance with Heat Conduction Calorimetry (QCMHCC) can overcome the limitations of classical calorimetric techniques to characterize molecular interactions by combining a microcalorimeter with a QCM biosensor. The TRP have developed and built a QCMHCC prototype that enables the rapid screening of chemical compounds compared to an immobilized pharmacological target to complement the CBMR´s drug-discovery platform.

Development of disease-related and drug-related biomarkers

The oncobiology group in collaboration with the TRP revealed that the kinase like protein TRIB2 confers resistance to several anti-cancer agents. Alongside several clinical research teams and pharmaceutical companies the TRP is validating and developing TRIB2 as a diagnostic marker for several human malignancies as well as a predictive biomarker for chemotherapy resistance.

Susceptibility genetic markers for breast cancer

The TRP is currently investigating genetic susceptibility to breast cancer, with particular attention directed towards regulatory genetic variation. The TRP is pioneering the first genome-wide association study in breast cancer using differential allelic expression, to precisely characterise the effect of cis-regulatory variation in breast cancer as a quantitative trait.

Drug delivery systems

The TRP is actively developing encapsulation strategies to provide alternate therapeutic administration approaches against local pulmonary diseases like cystic fibrosis and tuberculosis. The TRP is evaluating the effectiveness of several packaging formulations that have yielded promising results in our in vitro and ex vivo models.

Protein Nanoparticles for Molecular Delivery

The TRP has developed a unique panel of virus-like particles (VLPs) that are assembled within out in vitro systems. The TRP is developing these for the targeted intracellular delivery of biomolecules to specific cells or tissues, in particular these are being developed for treatment for HIV1 molecular therapy, cancer treatment, and iPS differentiation.