World-renowned for his research involving cell death and the immune system, Dr. Dixit has revolutionized the understanding of death receptor-mediated apoptosis and dramatically influenced the development of anticancer therapeutics.
Building upon previous work involving TNF-a, Dr. Dixit was the first to discover the presence and role of cysteine proteases (caspases) in programmed cell death. He discovered several caspases including caspases 3, 6, 7, and 9 and characterized their essential role in facilitating death receptor-mediated cell death via a coordinated signaling process, later referred to as a caspase cascade. He demonstrated that following ligand activation of death receptors, adaptor proteins such as FADD (Fas-associated protein with death domain) are recruited to the receptor and activate key initiator caspases such as caspase-8, which activates downstream effector caspases via proteolytic cleavage, ultimately resulting in DNA fragmentation and cell death.
In addition to FADD, Dr. Dixit also discovered that TRAF3 (TNF receptor-associated factor 3) functions as an adaptor molecule for CD40 (cluster of differentiation 40) signaling and that MyD88 (myeloid differentiation primary response gene 88) is the key signaling adaptor for IL-1. Furthermore, he discovered two families of pro-apoptotic caspase-related proteins, metacaspases and paracaspases, which have been shown to be important in the pathogenesis of cancer, namely MALT (mucosa-associated lymphoid tissue) lymphoma.
Dr. Dixit’s research involving caspases has also included investigating how these proteases affect innate immune responses. In these studies he discovered that caspases are an integral component of the inflammasome complex capable of activating various inflammatory processes as well as pyroptosis, a pro-inflammatory form of programmed cell death.
2016 AACR-GHA Clowes Memorial Award
2016 Dublin Dawson Prize in Genetics, Trinity College, Dublin, Ireland
2016 Gutenberg Research Award, Gutenberg Research College, Mainz, Germany
2013 Elected Member, National Academy of Sciences, Washington, DC
2012 Elected Member, Institute of Medicine
2012 Elected Member, Association of American Physicians
2012 Elected Associate Member, European Molecular Biology Organization
2011 Elected Fellow, American Academy of Arts and Sciences
1996 Warner-Lambert/Parke-Davis Award, American Society for Investigative Pathology
1989-1994 Established Investigatorship Award, American Heart Association
1983-1986 Josiah Macy Postdoctoral Fellowship Award
1980 Kamala Memorial Award
1980 Tommy-Adamson Award
1980 Best Student in Pathology Award, Kenya Medical Association