Gereau named Brown professor of anesthesiology

Robert W. Gereau IV, PhD, has been named the Dr. Seymour and Rose T. Brown Professor of Anesthesiology at Washington University School of Medicine in St. Louis.

The named professorship was announced by Washington University in St. Louis Chancellor Mark S. Wrighton and Larry J. Shapiro, MD, executive vice chancellor for medical affairs and dean of the School of Medicine.

Larry J. Shapiro, MD, (left), executive vice chancellor for medical affairs and dean of the School of Medicine, congratulates Robert W. Gereau IV, PhD, at his installation as the Dr. Seymour and Rose T. Brown Professor of Anesthesiology.

The professorship honors Washington University alumni Seymour Brown, MD, a 1940 graduate of the School of Medicine who served for more than 40 years as chief of anesthesiology at what was then St. John’s Mercy Hospital, and his wife, Rose Brown, who graduated from WUSTL in 1936 with a bachelor’s degree in education and biology. After completing her degree, Mrs. Brown served on the editorial staff of C.V. Mosby Publishing Co., editing medical books and journals.

They married in 1941, and shortly after that, Seymour Brown served as a physician on a destroyer in World War II, where he lived through many legendary naval battles including the battles of Midway and Guadalcanal. During the latter battle, his ship was torpedoed and sunk. Later in his military career, Brown was named chief of anesthesiology at naval hospitals in Great Lakes, Ill., and Mare Island, Calif.

When Dr. Brown completed military service, the Browns moved to Boston, where he studied anesthesiology at the Lahey Clinic and Mrs. Brown worked at Massachusetts Institute of Technology, editing books.

When they returned to St. Louis, Dr. Brown worked briefly at Barnes Hospital before starting the anesthesiology program at St. John’s and joining the clinical teaching faculty at Saint Louis University, where he served for more than 30 years. He also served terms as president of the Missouri state and the St. Louis societies of anesthesiology. Mrs. Brown assisted hearing-impaired students for 13 years and later worked as a real estate agent. She also volunteered at St. John’s Mercy Medical Center and at St. Luke’s Hospital for 20 years.

“Over the years, the Brown family’s generosity has helped fund scholarships for medical students, and this is one of two professorships the family established in anesthesiology,” Wrighton said. “The Browns also created an endowment for research in the Division of Gastroenterology in honor of their son, who was a gastroenterology resident here. We cannot thank the Browns enough for their extremely generous support.”

Dr. and Mrs. Brown were married for 65 years prior to Dr. Brown’s death in 2006. Mrs. Brown died in 2013. The couple had two sons, Alvin R. Brown, MD, and Donald E. Brown. Alvin Brown, who was a resident in gastroenterology at the School of Medicine, died in 2000. Donald Brown, an attorney, lives in Maryland with his wife and daughter.

In addition to his appointment in anesthesiology, Gereau also is a professor of anatomy and of neurobiology and is director of the Washington University Pain Center. He studies the molecular mechanisms involved in pain sensation, and his research includes basic laboratory work and translational studies of the pain response in people.

Most recently, Gereau’s laboratory has been involved in studies using optogenetics, which uses light signals to activate or deactivate nerve cells responsible for transmitting pain signals from the periphery to the brain. He is using tiny, light-emitting devices to map the molecular and cellular properties of neural circuits to better understand how those circuits transmit pain after nerve injury. Being able to visualize how the circuits connect and transmit pain signals could allow for the development of new treatments.

“Dr. Gereau’s work is at the forefront of pain research and is helping to better understand and alleviate chronic pain,” Shapiro said. “His efforts are vital to the development of new and more effective ways to treat the large numbers of patients with pain who could not previously be helped.”

Gereau graduated summa cum laude with a bachelor’s degree in biology from what is now Missouri State University. He earned a doctorate in neuroscience from Emory University School of Medicine and then completed a postdoctoral fellowship at the Salk Institute for Biological Studies before he became an assistant professor in the Division of Neuroscience at Baylor College of Medicine in 1998. He joined the Washington University faculty in 2004.

“Rob is a very talented scientist and a wonderful mentor for our residents, students and fellows,” said Alex S. Evers, MD, the Henry E. Mallinckrodt Professor and head of the Department of Anesthesiology. “His recent work using optogenetic techniques to turn pain signals on and off could lead to major breakthroughs in both the understanding and treatment of pain.”

(From left) Chancellor Mark S. Wrighton, Robert W. Gereau IV, PhD, Alex S. Evers, MD, and Larry J. Shapiro, MD, celebrate Gereau’s installation as the Dr. Seymour and Rose T. Brown Professor of Anesthesiology.

Gereau’s research has been supported continuously by National Institutes of Health (NIH) grants for the last 15 years, and he has served as a member and chair of multiple NIH study sections. He also serves on several editorial boards for scientific journals and is a member of the board of directors of the American Pain Society.

“The support from the Brown family for research in the Department of Anesthesiology has been tremendous,” Gereau said. “It is a great honor to receive this recognition for pain research, and I am very grateful to Don Brown and his family for their generosity in establishing this professorship. This support will help make our research effort more agile and innovative, and I hope it will help us to bring new treatments to the tens of millions of people who suffer with chronic pain.”

He has authored 80 peer-reviewed scientific publications, 26 invited publications and has been invited to deliver 85 lectures. During his career, Gereau also has mentored 34 pre- and postdoctoral trainees, as well as nine undergraduates and five high school students. In 2011, he received the Outstanding Faculty Mentor Award from the Washington University Graduate Student Senate. Among his other honors is a 2012 NIH Director’s Transformative Research Award for his efforts to treat pain using optogenetics.

Light — not pain-killing drugs — used to activate brain’s opioid receptors

Despite the abuse potential of opioid drugs, they have long been the best option for patients suffering from severe pain. The drugs interact with receptors on brain cells to tamp down the body’s pain response. But now, neuroscientists at Washington University School of Medicine in St. Louis have found a way to activate opioid receptors with light.

New research at Washington University in St. Louis shows that it’s possible to activate opioid receptors with light instead of pain-killing drugs. The discovery eventually may lead to new ways to relieve severe pain without the addictive properties and side effects posed by opiate drugs, such as morphine, OxyContin and Vicodin.

In a test tube, the scientists melded the light-sensing protein rhodopsin to key parts of opioid receptors to activate receptor pathways using light. They also influenced the behavior of mice by injecting the receptors into the brain, using light instead of drugs to stimulate a reward response.

Their findings are published online April 30 in the journal Neuron.

The eventual hope is to develop ways to use light to relieve pain, a line of discovery that also could lead to better pain-killing drugs with fewer side effects.

“It’s conceivable that with much more research we could develop ways to use light to relieve pain without a patient needing to take a pain-killing drug with side effects,” said first author Edward R. Siuda, a graduate student in the laboratory of Michael R. Bruchas, PhD, an assistant professor of anesthesiology and of neurobiology.

But before that’s possible, the researchers are attempting to learn the most effective ways to activate and deactivate the opioid receptor’s pathways in brain cells. Bruchas, the study’s principal investigator, explained that working with light rather than pain-killing drugs makes it much easier to understand how the receptors function within the complex array of cells and circuits in the brain and spinal cord.

“It’s been difficult to determine exactly how opioid receptors work because they have multiple functions in the body,” Bruchas explained. “These receptors interact with pain-killing drugs called opiates, but they also are involved in breathing, are found in the gastrointestinal tract and play a role in the reward response.”

So the researchers sought a way to limit opioid receptors to performing a single task at a time, and it turned out to be almost as easy as flipping on a light switch, according to Bruchas, Siuda and their collaborators, including co-first author Bryan A. Copits, PhD, a postdoctoral research scholar in the laboratory of Robert W. Gereau, IV, PhD, the Dr. Seymour and Rose T. Brown Professor of Anesthesiology.

By combining the rhodopsin protein, which senses light in the eye’s retina, with a specific type of opioid receptor called a Mu opioid receptor, the researchers were able to build a receptor that responds to light in exactly the same way that standard opioid receptors respond to pain-killing drugs.

From left, co-first author Bryan A. Copits, PhD, Michael R. Bruchas, PhD, and co-first author Edward R. Siuda used light to activate opiod receptors in the brains of mice.

When an opioid receptor is exposed to a pain-killing drug, it initiates activity in specific chemical pathways in the brain and spinal cord. And when the researchers shone light on the receptors that contained rhodopsin, the same cellular pathways were activated.

In a test tube and in cells, Siuda exposed the receptors to light and then watched as they released the same chemicals that standard opioid receptors release. Then, in mice, the researchers implanted a light-emitting diode (LED) device the size of a human hair into a brain region linked to the reward response. They injected the light-sensing receptors they had genetically manufactured into the same brain region. Neurons in that part of the brain release chemicals such as dopamine that create feelings of euphoria.

In decades of past opioid studies, researchers have observed mice and rats to press a lever to receive a dose of morphine, for example. The morphine would activate opioid receptors and the release of dopamine, and the animals would enjoy the response and press the lever again to continue feeling that reward sensation. This is one of the reasons opiates are so often abused in patients being treated for pain — people like the way the drugs make them feel as much as the pain relief  they provide — and rates of abuse have skyrocketed over the past ten years.

Working to deliver a similar reward sensation using light, the researchers put the mice into an enclosed chamber. In one part of the chamber, the lighted laser fiber-optic device stimulated the release of dopamine in the brain. When the animals left that part of the chamber, the light in the brain turned off. Soon after, the mice returned to the part of the chamber that activated the fiber-optic device so that the brain could receive more light stimulation.

“By activating the receptors with light, we are presumably causing the brain to release more dopamine,” Bruchas explained. “Rather than a drug such as morphine activating an opioid receptor, the light provides the reward.”

The researchers were able to vary the animals’ response depending on the amount and type of light emitted by the LED. Different colors of light, longer and shorter exposure to light, and whether the light pulsed or was constant all produced slightly different effects.

When a person takes an opioid drug such as Vicodin or OxyContin to relieve pain, such drugs interact with receptors in the brain to blunt pain sensations. But over time, patients develop tolerance and sometimes addiction. Opioids also can dramatically slow a person’s breathing, too, and typically cause constipation.

In theory, receptors tuned to light may not present the same danger. Siuda said it someday may be possible to activate, or deactivate, nerve cells without affecting any of the other receptors that pain-killing drugs trigger, although achieving that goal will be difficult.

Bruchas’ team is planning future studies that will use these receptors to test ways to control the brain cells that mediate pain and reward behavior with light rather than drugs.

The research was supported by a EUREKA award from the National Institute on Drug Abuse, the National Institute of Mental Health  and the National Institute of General Medical Sciences of the National Institutes of Health (NIH); grant numbers R01 DA037152, F31 MH101956, K99 DA038725, TR32 GM108539 and NSTR01 NS081707. Additional funding from a W.M. Keck Fellowship in Molecular Medicine; and the Howard Hughes Medical Institute.

Siuda ER, Copits BA, Schmidt MJ, Baird MA, Al-Hasani R, Planer WJ, Funderburk SC, McCall JG, Gereau RW, Bruchas M. Spatiotemporal control of opioid signaling and behavior. Neuron, published online April 30, 2015.

Washington University School of Medicine‘s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’shospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.