Bio-Science: Kenneth Bernstein, MD

Above all else, though, Bernstein sees beauty in the biology of human beings.

"The complexity that goes into a human—the kidney, the heart, the endocrine system, the eye, the ear and, of course, the brain—is extraordinarily beautiful. The more you know about biology, the more it's breathtaking," said Bernstein, professor of Pathology and Laboratory Medicine and Biomedical Sciences at Cedars-Sinai.

Beauty and biology aren't Bernstein's only counterintuitive couplings.

"I think science is an art form because there's a real creativity to it. You have to be creative to ask unusual scientific questions," Bernstein said.

During his four-decade career, Bernstein has raised reams of unusual scientific questions leading to important discoveries, particularly regarding the renin-angiotensin system and its angiotensin-converting enzyme (ACE). This system is a key regulator of blood pressure and electrolyte homeostasis. ACE produces the peptide angiotensin II, which directs the system's biological activity.

Bernstein is recognized globally for cloning and characterizing the gene for the angiotensin II receptor, now known as the AT1 receptor. This receptor affects adrenal glands, blood vessels, brain, gut, heart, kidneys, nerves and smooth muscles—all of which work together to maintain blood pressure. Bernstein's discovery, published in the journal Nature, has been cited more than 1,300 times. It provided a powerful tool for understanding the multisystem process involved in blood pressure regulation.

That discovery has been followed by myriad scientific contributions, including the creation of several novel mouse models of ACE expression, a project begun during Bernstein's 1993 sabbatical with molecular geneticist Mario Capecchi, PhD, at the University of Utah School of Medicine. Capecchi was the co-winner of the 2007 Nobel Prize in Physiology or Medicine for discovering a method of breeding mice in which a specific gene is turned off, known as knockout mice.

Bernstein has used genetically modified mice to study the role of ACE in Alzheimer's disease, blood pressure control, immune response and more.

Jorge F. Giani, PhD, assistant professor in the Cedars-Sinai Department of Biomedical Sciences, has collaborated with Bernstein on some 20 studies. "A prime example of Ken's ability to see things differently is his approach to studying ACE. For more than 40 years, ACE has been associated with blood pressure. Ken started studying if ACE also could be involved with the immune response. This is a new and important direction no one else thought to explore," Giani said.

Bernstein's bent for innovation has garnered several awards, including the American Heart Association (AHA) Novartis Award for Hypertension Research, the AHA’s Basic Science Prize and an AHA Distinguished Scientist designation.

The product of a stay-at-home mother and a mechanical engineer father, Bernstein was born and raised in West Hartford, Connecticut, along with his younger sister. When he was a preschooler, he recalled, "my father would take me outside to look at the stars, and I would drive him crazy by asking an enormous amount of questions. From the time I was a little boy, I wanted to be a scientist."

Bernstein's educational path brought him to Dartmouth College in New Hampshire, then to the New York University School of Medicine and pathology residencies at New York-Presbyterian Hospital and the National Institutes of Health (NIH) Laboratory of Pathology.

At the NIH, he met his wife-to-be, Ellen Nielsen, a technician working at a neighboring NIH lab. The couple exchanged vows in 1983, and in 1987 moved to Atlanta when Bernstein joined Emory University's Department of Pathology as assistant professor.

The Bernsteins called Atlanta home for 21 years and welcomed three daughters, who today are pursuing careers in nursing, construction management and data analysis.

Atlanta also was the birthplace of the Bernsteins' passion for collecting antique clocks.

"It was our 15th wedding anniversary and I said, 'Let's get an older clock as a marker of our time together,' " Ellen Bernstein recalled. "The next thing I knew, Ken and I were members of the National Association of Watch and Clock Collectors." Today, the couple has more than two dozen clocks, including a museum-quality, 18th century piece created by renowned French clockmaker Étienne Le Noir.

Both Bernsteins joined Cedars-Sinai in 2008, he as professor of Biomedical Sciences and Pathology and Laboratory Medicine and director of Experimental Pathology, and she as a research associate II in the Department of Biomedical Sciences; her current position is research associate III.

Derick Okwan, MD, PhD, also traded Atlanta for Los Angeles in 2008. At the time, he was a graduate student in Bernstein's Emory University lab. He spent the next three years finishing his doctoral studies with Bernstein at Cedars-Sinai before returning to Emory. The two men have collaborated on several studies.

To Okwan, who recently rejoined Cedars-Sinai as an independent investigator in the Department of Pathology and Laboratory Medicine, Bernstein has been more than a mentor. "Ken definitely has been a father figure to me," Okwan said. "Not only has he wholeheartedly invested in my development as a scientist, he has also been interested in my personal growth as a human being. Ken is a one-stop shop; whether you need career direction or personal advice, he's there for you."

At 68, Bernstein remains an enthusiastic scientist engaged in several promising studies. Recently, he discovered that ACE overexpression can create "turbocharged" mitochondria—the power plants of cells. The result, he hypothesizes, may be more powerful cells and, potentially, a stronger immune response that could help treat a variety of infectious, malignant and chronic diseases.

"This was a totally new and unexpected finding," Bernstein said. "It's a great thing to discover something totally new and unexpected."

Some might even say it's a beautiful thing.