PARP14 interactomes in disease: close the loop between PARP14 function in vivo and in vitro
We will dissect the effects of drugging PARP14 on its molecular interaction networks and pathobiology
This project will study a protein called PARP14 and how it interacts with other molecules in the body. PARP14 is found in higher amounts in people with inflammatory diseases like skin conditions (atopic dermatitis or psoriasis) and mild asthma but is present at lower levels in healthy people. By learning more about PARP14, we will uncover new ways to treat these illnesses. Other proteins interacting with PARP14 could provide additional treatment options. Ribon Therapeutics Inc. (Cambridge, MA) will be collaborating with Dr. John LaCava's Laboratory of Macromolecules and Interactomes (at the UMCG, Groningen) to uncover the secrets of PARP14 in health and disease.
Most drugs work by targeting proteins to change their actions, but only a small percentage (1-2%) of proteins can be targeted using available drugs. By instead looking at protein interactions, we can open new opportunities: this project explores traditional and new ways to approach drug development. We will block PARP14s main function, using genetics, biochemistry, and various drugs, and study the effects on other molecules,
Dr. LaCava’s team will be execute research that involves protein interactions, using unique in-house capabilities. Ribon Therapeutics will provide the new drugs that will be tested in the research and will work with Dr. LaCava’s team to understand how cells respond. Ribon Therapeutics specializes in developing new drug treatments that target PARP proteins. Together, the synergy between these teams will rapidly advance therapies that target PARP14 but will also advance the concepts and techniques needed to drug protein interactions, in general.
Deliverables will include – quantitative descriptions of PARP14 interactions with other proteins and knowledge of how those interactions are affected by treatments with drugs and drug candidates. Once differences are defined, opportunities to exploit the differences (candidate secondary targets) with drugs, rather than PARP14 (the primary target) may also be explored.
The project started very well scientifically and was even extended to a second year. However, unfortunately, the company partner Ribon had some financial mismanagement issues starting in Autumn 2023 that resulted in Ribon going out of business and in full liquidation in March 2024. Despite several efforts to make contacts with the company, all attempts have failed and it was decided to terminate the project earlier than the initial project timeline.
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