In Memoriam: Dr. Bert O'Malley

O’Malley’s lab discovered and was the first to solve the structure of a functional receptor-coactivator complex on DNA capable of regulating gene transcription in vitro. In addition, he showed that steroid receptor coactivator-2 (SRC-2), which is highly elevated in a variety of tumors, is likely implicated in metabolic coordination of cancer metastasis, opening the possibility of therapeutically targeting the SRC-2 pathway. 

His work with steroid receptor coactivator-3 (SRC-3), a prognostic marker for aggressive human breast cancer, showed that small-molecule inhibitors that directly bind SRC-3 cause selective degradation of the complex, hereby killing cancer cells with no observable toxicity. Small-molecule inhibitors represent a new type of oncologic drugs that target coactivators.

In addition, Dr. O’Malley’s work showed in a mouse model of heart disease, that stimulating SRC-3 with small-molecule MCB-613 initiated a complex cascade of events in tissue repair and modulation of the inflammatory response that reduced fibrosis, attenuating loss of cardiac function after myocardial infarction. These findings open the possibility of novel therapies to regulate the progression of heart failure via SRC-3.

His work also revealed a role for SRC-3 in regulatory immune T cells (Tregs) that promote cancer growth by inhibiting anti-cancer immune responses. He also showed that SRC-3 is significantly enriched in both murine and human Tregs. Inhibiting SRC-3 in Tregs in the lab stopped them from reducing the anti-tumor response, suggesting that modulating SRC-3 in Tregs might help control cancer growth.

Memberships

Dr. O’Malley was a member of the National Academy of Sciences, the National Academy of Medicine, the American Association of Physicians and the National Academy of Inventors. He won the National Medal of Science in 2007 and received more than 65 honors and science prizes in his career.

Dr. O’Malley was a fellow of the American Academy of Arts and Sciences, the American Academy of Microbiology, the American Association for the Advancement of Science and the American Association of Cancer Research. He received honorary doctorate degrees from the Karolinska Institute, New York University, the National University of Ireland, the University of Maryland, the University of Pittsburgh and the University of Athens, Greece.

Awards and Honors

His awards and honors include:  

• Ernst Oppenheimer Award
• Gregory Pincus Medal
• Lila Gruber Award
• Borden Award
• Axel Munthe Award
• Bicentennial Medallion of Distinction (University of Pittsburgh)
• Kodak Award
• Doisy Lecture Award
• D.R. Edwards Medal
• E.E.S. Transatlantic Medal
• George W. Beadle Award
• Solomon Berson L. Ad. (Amer. Phy. Soc.), Pioneer Award
• Woods Hole, Biolink Scientist of the Year Award
• Vanderbilt Distinguished Medical Award (Alumni Association)
• Bowman Distinguished Geneticist Award
• Dickson Prize (1979)
• Fred Conrad Koch Medal (1998)
• Rodbell Award (National Institute of Environmental Health Science) (2001)
• Feltrinelli International Prize in Biology (2001)
• Brinker Award in Breast Cancer Research (2001)
• Antonio Feltrinelli International Prize for Biology (2001)
• Induction into the Royal Academy of Medicine (2003)
• Pasarow Award in Cancer Research (2006)
• Carl Hartman Award for Reproductive Research (2007)
• Steven Beering Award in Medical Research (2009)
• Ernst Schering Prize (2011)
• Ipsen Foundation Research Prize in Endocrinology (2013)
• Dale Medal from the Society for Endocrinology (2014)
• Outstanding Innovation Award (End.Soc.) (2015)
• Jensen Lifetime Achievement Award (U.Cinn.) (2018)
• Louisa Gross Horwitz Prize (2018)