The IBRI has a proven ability to overcome organizational barriers to facilitate complex, multi-organizational projects. Our researchers are actively leading inquiry and analysis in regenerative medicine, single cell bioanalytics, and advanced data science.
Determining the Impact of Diabetes Progression
Cardiovascular incidents are the leading cause of death in people with type 2 diabetes. But IBRI Research Fellow Michael Pugia, PhD, wants to change that.
Using samples from the Fairbanks Institute Tissue Core, Pugia is testing the accuracy of new diagnostic assays designed to detect acute inflammation, auto-immunity and insulin resistance in diabetics and determine their impact on disease progression. These changes in the immune system lead to tissue damage, which serve as an early indicator of cardiovascular disease.
Because the Fairbanks samples are linked to individuals’ electronic medical records, Pugia is able to test the blood samples given more than 20 years ago and then review the current records to determine how accurate his test is in predicting which patients would develop some form of cardiovascular disease over time.
Pugia hopes to provide a simple blood test that can accurately predict a person’s likelihood of developing cardiovascular disease so doctors can offer early intervention and improve long-term outcomes for those patients. His research is also leading to an antibody that might be used to prevent cardiovascular incidents from happening in these patients.
Better Predicting Safe Molecules
The high cost of developing any molecule for use as a new drug or agricultural product makes accurate early assessment of the safety of those molecules critical. More accurate early predictions about the safety of a molecule can potentially save companies time and millions in development costs with a “fail fast” model, while focusing research activities on molecules that are more likely to meet regulatory requirements and societal expectations.
Two of Indiana’s global life sciences companies, Dow AgroSciences and Eli Lilly and Company, have both independently developed analytic pipelines to assist their scientists in interpreting the safety assessment data to determine the potential risk of new molecules. The Indiana Biosciences Research Institute (IBRI) collaborated with these companies to take their independently-developed analytic pipelines and develop a common platform to identify and quantify potential compound toxicity from the transcriptomic data. This platform uses current industrial experience and decision-making to improve adoption by the larger research and regulatory communities of these newer methods to rapidly assess compound toxicity and biological rationales. It also enables multiple standard informatics methods to be run consistently and compared across existing public data sets.
In these early discovery experiments, detailing the disruptions of the biological pathways by these compounds allows scientists to better predict how the study results may translate to other human or environmental impacts.
The IBRI Diabetes Center, led by Dr. Robert Considine, includes his lab, the Considine Lab, the Lilly Diabetes Center of Excellence (LDCE), the Eizirik Lab led by Dr. Decio Eizirik, and the Regenerative Medicine and Metabolic Biology Group (RMMB), led by Dr. Teresa Mastracci and her lab, the Mastracci Lab.
Instructing Proper Pancreas Development
Why does the pancreas remain healthy in some people and become diseased in others? It’s a complex question that Dr. Teresa Mastracci is trying to answer by deconstructing the biological pathways that direct cell development, differentiation and regeneration in the pancreas. By understanding the role different genes and proteins, especially enzymes, play in the development of the pancreas, Mastracci will be able to identify potential drug targets that could be used to better treat or possibly reverse diabetes.
A study currently under way in the Regenerative Medicine and Metabolic Biology group found that the enzyme called deoxyhypusine synthase (DHS) is a critical link between the polyamine and hypusine biosynthesis pathway, mRNA translation (the process by which proteins are made), and the differentiation of cells in the pancreas. The polyamine and hypusine biosynthesis pathway is required for cells to grow and is essential for embryonic development. Data collected in the study suggest that DHS may be also be required for the translation of specific mRNAs needed for pancreatic cells to differentiate into the various cells that comprise a healthy pancreas. Without DHS, the study has identified that the synthesis of key proteins were severely reduced, resulting in abnormal metabolism and postnatal growth.
Being established to focus on human health concerns through the development and manufacturing of therapeutic antibodies and vaccines.