Distinguished Scientists 2013 -- Kenneth E. Bernstein, MD, FAHA
Dr. Kenneth E. Bernstein received an M.D. degree from New York University in 1978. After a residency in pathology and a research fellowship at NIH, Dr. Bernstein worked at Emory University and then Cedars-Sinai Medical Center in Los Angeles. Dr. Bernstein has studied the physiology and biochemistry of the renin-angiotensin system since 1987. His research concerns two important areas: the angiotensin II AT1 receptor and angiotensin-converting enzyme (ACE). Dr. Bernstein’s cloning of cDNA encoding the AT1 receptor in 1991 was a major discovery in understanding the RAS. Bernstein followed with a series of important papers showing that the seven transmembrane AT1 receptor signaled, in part, using several intracellular kinase pathways, including the Jak-STAT pathway. His work helped overturn dogma concerning intracellular signaling by seven transmembrane receptors and provides insight into why angiotensin II has many physiologic effects in addition to blood pressure control.
In 1988 and 1989, Dr. Bernstein’s laboratory was one of two to first clone and characterize the structure of ACE. Bernstein was also the first to discover that the ACE gene contains two distinct promoter regions, a promoter used by endothelium to make somatic ACE, and an intragenic testis-specific promoter used by developing sperm to make a smaller version of the ACE protein. The catalytic activity of this testis ACE is necessary for normal male fertility. In 1999, Dr. Bernstein collaborated with Dr. Mario Capecchi to produce an important technical advance that simplified how one can use Cre-lox vectors for targeted homologous recombination in stem cells. In recent years, Dr. Bernstein’s lab created a series of mice with unique mutations in the ACE gene, focusing on the physiologic role of ACE in individual tissue types, such as the heart and the kidney. These animal models addressed the role of local vs systemic angiotensin II generation, as well as the physiologic role of ACE apart from blood pressure control. They identified a novel role of angiotensin II in erythropoiesis. They suggested that the ACE substrate Ac-SDKP may help protect the lung against fibrosis following chemotherapy. They indicated a role of ACE in the processing of immune peptides that signal self vs. foreign to the immune system. And they provided the first observation that mice over-expressing ACE in macrophages have a markedly enhanced immune response to tumors and bacterial infections. Finally, Bernstein’s lab has identified important functional differences between the two catalytic domains of ACE. This has clinical implications in that other labs have developed prototypic ACE inhibitors specific for each ACE catalytic domain.
Dr. Bernstein was an AHA Established Investigator from 1988-1993. In 2005, he shared the AHA’s Novartis Prize for Hypertension Research with Dr. Barry Brenner. In 2007, Dr. Bernstein received the AHA’s Basic Research Prize. Dr. Bernstein has lived for over 31 years with the ACE of his heart, his wife Ellen.