For more than 40 years, UCLA bioengineering distinguished professor Wentai Liu has pioneered technologies that combine electronic and biological properties to help patients regain their physical abilities and improve quality of life, such as helping the blind see and the paralyzed walk.
Now, his work focuses on using electrical signals to alleviate the serious side effects of chemotherapy, detect and delay onset of Alzheimer’s disease, and improve treatment for post-operative or other gastrointestinal ailments.
Following are some of the ways Liu’s technological developments are changing lives.
Groundbreaking work includes the first bionic eye for the blind and a novel electrode array for paralyzed individuals to regain mobility
First at North Carolina State and then at UC Santa Cruz, Liu co-directed the research and development of a landmark electronic retinal implant that helped restore eyesight to the blind, funded by the National Science Foundation’s Biomimetic MicroElectronics Systems Research Center. Approved by the U.S. Food and Drug Administration in 2013 after 25 years of research, the Argus II Retinal Prosthesis System helps restore eyesight with a tiny yet powerful computer chip implanted in the eye, effectively sidestepping the damaged photoreceptors to “trick” the eye into seeing.
Since joining the UCLA Samueli School of Engineering in 2011, where he also holds a joint faculty appointment in electrical and computer engineering, Liu has been part of a team working to help people with spinal cord injuries walk again. In 2015, Liu and his colleagues developed a multi-electrode array device that uses electrical signals to activate nerves in the spine without a direct connection to the brain. A member of the Brain Research Institute and the California NanoSystems Institute at UCLA, he has also been working on technologies to improve the operation and signal accuracy of brain–machine interfaces, which allow the brain to communicate directly with a computer or prosthetic limb.
Research uses electrical neuromodulation to treat painful gut diseases
For more than a decade, Liu has also conducted research on dysmotility issues in the gastrointestinal tract where the muscles and nerves of the digestive system are not functioning properly, leading to abnormal movement of food through the esophagus, stomach, small intestine and colon. This condition can cause abdominal pain, vomiting, nausea, bloating and constipation. Liu’s team has focused on postoperative ileus, or POI — caused by complications after surgery — and Hirschsprung’s disease, a birth defect that affects the large intestine.
Funded by both the NSF (for developing POI-related technologies targeting the GI tract) and the National Institutes of Health (for functional mapping of the colon), Liu’s research involved using electrical neuromodulation for direct electrical stimulation of the colon and a pair of nerve cell clusters in the upper abdomen, known as the celiac ganglia, that regulate the autonomic nervous system’s functions in the abdominal organs.
The research culminated in the development of a small, implantable wireless extraluminal gastrointestinal modulation device, or WEGMD, that can be inserted simultaneously during an abdominal surgery. The device utilizes wireless technology to regulate bowel movements and treat conditions related to abnormal gut dysmotility by delivering electrical pulses to the GI tract from outside the intestinal lumen, which is the hollow space inside the intestines that allows digested food to pass through. Liu’s team is working on making the WEGMD into a much smaller, pill-shaped device that can be implanted in the gut, with the ultimate design goal being an ingestible system.
‘Electropeutics’ relieve pain from cancer treatments and other chronic diseases
Most recently, Liu has turned his attention to an emerging class of therapies he has dubbed “electropeutics.” Working with doctors and researchers at Taiwan’s National Cheng Kung University, Liu and his colleagues have discovered that electrical stimulation can be used to reduce serious side effects of chemotherapy treatments.
Chemotherapy uses anti-cancer drugs to kill or slow down rapidly growing cells in the body. However, these drugs not only target cancerous cells but also damage healthy ones — especially those in bone marrow and nerves. This results in lowered counts of platelets, red blood cells and infection-fighting white blood cells. While other drugs can be prescribed to help manage these conditions, they often come with their own serious side effects such as chest pain, nausea, shortness of breath, cold sweats and low blood oxygen levels. These unpleasant, debilitating side effects can sometimes cause people undergoing treatments to stop taking the medication that was supposed to help them manage symptoms from chemotherapy.
Now, a team led by Liu has developed a new technique called electrical sympathetic neuromodulation, which leverages electrical stimulation to prompt bone marrow to produce blood cells and platelets. The method offers an alternative to currently used pharmaceuticals that come with adverse side effects.
“Historically, neuromodulation has focused on restoring the functionality of organs, something our group has done with lost sight, paralysis, gastrointestinal tract motility and damaged nervous systems,” said Liu, who directs the Biomimetic Research Lab at UCLA. “More recent research suggests that neuromodulation can also be applied to regulating disease states and conditions, which represents a paradigm shift in the field.”
In a paper published in the journal Small Methods, the researchers used electrical stimulation on the sciatic nerve along the rear thigh of rats. They found the stimulation caused production of white blood cells at a level similar to that of granulocyte colony-stimulating factor, a commonly prescribed drug during chemotherapy. More importantly, they found the technique also stimulated the production of blood platelets while reducing the effects of nerve damage, another side effect of chemotherapy.
The researchers have filed for a U.S. and international patent for the technique, which they suggest could be adopted as an alternative or companion for medicines that address chemotherapy effects.
“This emerging area of bioelectronic medicine has the potential to transform health care where drugs will not be the only option,” said Liu, who is also the co-founder of Aneuvo Biomedical Inc. “The technique can be applied not just to treatments for someone undergoing chemotherapy, but also for other conditions as well, including chronic constipation.”
Liu’s research on electrical sympathetic neuromodulation applications is supported by Taiwan’s Ministry of Science and Technology, Ministry of Health and Welfare and Ministry of Education, with additional funding from UCLA through Liu’s distinguished professorship, the Yushan Fellow Program and NCKU.
A machine-learning model to predict Alzheimer’s onset and progression
While the exact cause of Alzheimer’s disease is still unknown, multiple factors are believed to contribute to its development. Among them are clumps of a protein called amyloid beta that accumulate in the hippocampus, a part of the brain located in the temporal lobe near the temples and ears that helps with memory, learning and spatial navigation. Memory decline is found prior to the appearance of both the amyloid plaques and brain atrophy in animal models.
Working in collaboration with the UCLA Brain Research Institute, Liu’s lab is proposing a longitudinal study to better understand and diagnose Alzheimer’s disease in its early stages. To achieve this, the team uses a customized wireless intracranial electroencephalography, or iEEG, recording platform to continuously monitor the hippocampal iEEG activity, cognitive performance, the accumulation of amyloid plaques and the cells that promote or inhibit the transmission of information within the neural network. Using electrophysiology to study the electrical activity of brain cells may help early diagnosis and detection of Alzheimer’s and slow its progression.
Liu’s team is also investigating the spatial–temporal dynamics of Alzheimer’s biomarkers in its early progression through clinical and animal studies. The researchers are working on developing a more versatile machine learning-based model using large datasets to predict amyloid accumulation, allowing for early treatment decisions before amyloid plaques form. The difference in time could slow the disease progression and help make treatment more effective.
Improvements in health and quality of life through bioengineering and medicine collaboration
From the bionic eye to the latest brain–machine interface technology for early detection and treatment of Alzheimer’s disease, Liu has devoted his research to furthering the understanding of diseases and finding innovative treatment solutions. Throughout his long career, including the early days when bioengineering and biomedicine were still in their infancy, Liu has collaborated with physicians to steer his engineering expertise toward solving problems in health and medicine.
“My father always wanted me to be a doctor, but I chose engineering,” Liu said in a 2013 interview. “Now I realize I’ve come full circle, working with colleagues in medicine to help people.”