Paul Negulescu

Early life and education Negulescu was born in San Francisco to first-generation immigrants from Romania. His father was a surgeon, He has a brother. Negulescu joined Aurora Biosciences in 1996 as one of the first employees. He became Senior Vice President of Discovery Biology in 1999. When Vertex Pharmaceuticals acquired Aurora Biosciences in 2001, he was appointed Senior Vice President of Research.

Research Negulescu's research focuses on the therapy of cystic fibrosis. Cystic fibrosis can be caused by any of the thousands of identified mutations in the CFTR protein, an ion channel that allows chloride ions to pass through. These mutations have been classified into Class I to V, with Class III mutations causing defective channel gates in CFTR despite normal expression of the protein. Via high-throughput screening, his team at Vertex Pharmaceuticals discovered ivacaftor, a small-molecule potentiator that increases the probability that mutated CFTR gates will open. Ivacaftor was approved by the Food and Drug Administration (FDA) for cystic fibrosis patients with one specific Class III mutation in 2012, and has since been approved for mutation classes as well. Of note, the expanded approval in 2017 was based solely on in vitro data, due to the small number of patients carrying those rare mutations making clinical trials impossible.

Negulescu also led the discovery of another cystic fibrosis drug, lumacaftor, which is known as a "corrector" as it acts as a chaperone to help the CFTR protein fold correctly. Thus, it can be used in patients with Class II mutations, which create misfolded CFTR protein that cannot reaching the cell surface. Again with high-throughput screening, Negulescu and his team found that lumacaftor can correct F508del-mutated CFTR protein. It was later found that the drug was not effective enough when administered on its own, but was so when administered together with ivacaftor. The FDA approved this drug combination in 2015. Further research led to the discovery of tezacaftor and elexacaftor, 2 other correctors of the CFTR protein. The triple combination elexacaftor/tezacaftor/ivacaftor was approved by the FDA in 2019.

Honors and awards 2018 - Warren Alpert Foundation Prize 2023 - Wiley Prize 2024 - Breakthrough Prize in Life Sciences

Personal life Negulescu met his wife, Debbie, during his time at the University of California, Irvine.