UCI Biomedical Engineering Discovery Magazine Fall 2019

BME DISCOVERY DEPARTMENT OF BIOMEDICAL ENGINEERING

FALL 2019

Inspiring Engineering Minds to Advance Human Health

FROM THE CHAIR

Greetings from beautiful Southern California – a region with mild weather year-round and home to many beautiful beaches.

But for our BME family, it’s not just about the sun and sand; we are fortunate to live in one of the nation’s largest biotech, pharmaceutical and medical device hubs, which makes our research and educational mission more exciting, relevant and grounded. We are also excited to continue strengthening ties with the UCI School of Medicine, where our faculty collaborate with clinicians to translate their discoveries from the benchtop to the bedside.

The latest example is our newest faculty member, Joshua Mauney – an associate professor and the Jerry D. Choate Presidential Chair in urology tissue engineering. Josh has a dual appointment in the BME and urology departments. He is joining us from Harvard Medical School, where he has done exciting work at the intersection of tissue engineering and biomaterials for urinary and gastrointestinal tract repair. We are happy to welcome Josh into our BME family and look forward to his continued success as well as fresh ideas and perspectives.

As we welcomed new faculty on the one hand this year, we bade farewell to another. Bruce Tromberg – a dear friend and a wonderful colleague – took over as the director of the NIH’s National Institute of Biomedical Imaging and Bioengineering. While Bruce’s wisdom and contagious optimism will be sorely missed at faculty meetings and retreats,

I cannot help but feel happy for him. I also take comfort in knowing that bioengineers have a strong advocate at the NIH and beyond. I am incredibly proud of his accomplishments, and I look forward to his leadership and vision in this new role.

Our BME faculty are continuously recognized for their excellence and significant contributions to engineering, science and technology. In the following pages, you will read about many of these accomplishments from the past year. Hand-in-hand with the accolades goes the groundbreaking research from our students, postdocs and faculty.

In this magazine, you will find captivating stories such as speeding up directed evolution, which may lead to the development of better enzymes or proteins. It may also help address problems such as drug resistance. Our researchers also found a way to engineer joint tissues and implant them in animals with promising results. If successfully translated to humans, this approach may alleviate joint problems for which there are currently no satisfactory treatment options. You will also learn how a nanotechnology treatment derived from bone marrow stem cells can be used to reverse the negative effects of multiple sclerosis and perhaps other autoimmune and neurodegenerative disorders. To keep our research thriving, our faculty have been very successful in securing extramural funding from major federal agencies and foundations.

This publication is about the people I am proud to call colleagues. I invite you to read on to get to know us better. I also invite you to visit us on the beautiful UCI campus or engage with us in other meaningful ways.

Sincerely, Zoran Nenadic, D.Sc. William J. Link Chair and Professor Department of Biomedical Engineering, University of California, Irvine

PAGE 4 Researchers are using live cells to boost directed evolution, speeding up and simplifying the process.

PAGE 14 A rehabilitative tool could help stroke survivors reestablish important brainmuscle connections, improving their gait and their quality of life.

CONTENTS

PAGE 20 Professor takes research into the marketplace with tools that sharpen and revolutionize drug discovery and development.

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By the Numbers

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Genetic Architect

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Research and Funding

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Rewiring the Brain

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Recognition and Reward

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Journey to Lab-on-a-Chip

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Accolades

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Diabetic Support

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Directory

BME DISCOVERY is published annually by the UCI Samueli School’s communications staff for the Department of Biomedical Engineering.

Chair: Zoran Nenadic, D.Sc. BME Dept. Administrator: Cathy Ta Editor-in-Chief: Shelly Nazarenus Art Direction: Michael Marcheschi, m2dg.com Publisher: Mike Delaney, Meridian Graphics

ON THE COVER: Outgoing department chair Abe Lee has devoted his career to solving problems linked to health care, pharmaceutical efficacy and environmental well-being with the help of advanced microfluidic devices. Now Lee and two partners have launched a bioscience startup to advance personalized medicine platforms.

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BY THE NUMBERS

UC IRVINE DEPARTMENT OF BIOMEDICAL ENGINEERING Founded in 2002, the growth of biomedical engineering in the Samueli School has been rapid. The department merges UCI’s strengths in medicine, biological sciences and engineering. BME faculty are competitive in garnering extramural grants, with expenditures topping $30M on an annual basis. Strong ties with many of Orange County’s more than 300 biomedical device and biotech companies provide students and faculty with distinct opportunities to solve contemporary medical challenges.

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GRADUATE STUDENTS (FALL 2018) 2

M.S., PH.D. DEGREES

STUDENT POPULATION

518

UNDERGRADUATE STUDENTS (FALL 2018)

Biomedical Engineering

B.S. DEGREES Biomedical Engineering Biomedical Engineering: Premedical

UCI Department of Biomedical Engineering

RESEARCH & EXPENDITURES

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FACULTY & RECOGNITION

FULL-TIME FACULTY

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WORLD-CLASS CENTERS, including 1 NSF I/UCRC and 2 NIH P41

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NATIONAL ACADEMY OF INVENTORS

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NSF CAREER AWARDS

RESEARCH EXPENDITURES (2017-18)

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RESEARCH THRUSTS

AFFILIATED FACULTY Biomedical Computational Technologies Biomedical Nanoscale Systems

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NIH NEW INNOVATOR AWARDS

Biomolecular/ Genetic Engineering Biophotonics Cardiovascular

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DARPA YOUNG FACULTY AWARD

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DISTINGUISHED PROFESSORS

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$35.7 MILLION

Neuroengineering Tissue Engineering

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ENDOWED CHAIR AND PROFESSORSHIPS

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FEATURE

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UCI Department of Biomedical Engineering

GENETIC ARCHITECT

Live cells boost directed evolution BRIAN BELL

STEVE ZYLIUS 5

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N A PROCESS KNOWN AS DIRECTED EVOLUTION, SCIENTISTS REENGINEER BIOMOLECULES TO FIND ONES THAT PERFORM BENEFICIAL NEW FUNCTIONS. The field is revolutionizing drug development, chemical engineering and other applications, but to realize its promise involves painstaking and time-consuming laboratory work.

In a study published last fall in the journal Cell, Samueli School researchers reported that they have accelerated and simplified directed evolution by having live cells do most of the heavy lifting. By inserting a specially engineered DNA replication system into yeast, the scientists were able to coax selected genes to rapidly and stably mutate and evolve as the host yeast cells reproduced.

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“By moving high rates of diversification into cells in a targeted manner, we can grow and pressure those cells to evolve into something new from any genes of our choosing,” says first author Arjun

Ravikumar, who earned his Ph.D. in biomedical engineering at UCI. “Our work has reduced evolution to be an extremely rapid, straightforward and scalable process.”

Previously, for scientists to screen biomolecules to see if a desired function has been achieved, they needed to build a DNA library in a test tube and insert that DNA into the cells, a laborious and difficult process. The UCI team has eliminated this step entirely in its new approach, letting the cell’s internal machinery do all of the work.

According to senior author Chang Liu, assistant professor of biomedical engineering, when using directed evolution to create a better enzyme or protein – the work that won the Nobel Prize in Chemistry this year – the number of evolutionary cycles becomes very important, because each one can be seen as a step toward a new or improved function. “But if each cycle requires repetitious test-tube DNA molecular biology processing, you can only reasonably go through a few iterations,” he says.

UCI Department of Biomedical Engineering

“In contrast, natural evolution runs cycles continuously, essentially by culturing cells over time in an environment that pressures them to develop some new function; the problem from a biomolecular engineering standpoint is that the process is very slow,” Liu adds. “We have figured out a genetic architecture that allows biomolecular evolution to be very fast.”

In addition to speeding and simplifying directed evolution, Liu says this new technique can allow scientists to perform additional types of experiments that they had difficulty doing in the past. For example, in their study, the UCI researchers described how they evolved an enzyme in 90 replicate experiments in order to figure out all the ways it could adapt to a certain condition – in this case how a malarial target could develop resistance to a certain drug.

“There are many ways of solving a particular evolutionary challenge such as drug resistance, so the ability to run evolution experiments at the scale that we have allows us to capture and understand more of those possibilities, giving us therapeutically relevant insights into how resistance arises,” Liu says.

Future work will focus on getting the new platform to continuously evolve diseasefighting antibodies and valuable enzymes for drug synthesis.

“Instead of having to inject an antigen into an animal in order to isolate an antibody, imagine just putting it into a culture of yeast cells and having it come out as a specific antibody,” he says. “That could revolutionize how these and other protein drugs are discovered and developed.”

Frances Arnold – the Linus Pauling Professor of Chemical Engineering, Bioengineering & Biochemistry at the California Institute of Technology, who won the 2018 Nobel Prize in Chemistry for her pioneering contributions in the field – said, “Directed evolution is a powerful way to build new proteins, but it can certainly benefit from technological innovations.

The technique that Professor Liu and Dr. Ravikumar have developed will stimulate new applications and new avenues of investigation, which will continue to expand our ability to compose new DNA.” This research project was supported by the National Institutes of Health, the Defense Advanced Research Projects Agency, the Sloan Research Fellowship, the Beckman Young Investigator Award, the Dupont Young Professor Award and startup funds from UCI Applied Innovation.

“We have figured out a genetic architecture that allows biomolecular evolution to be very fast.”

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RESEARCH & FUNDING

UCI ENGINEERS AIM TO PIONEER TISSUEENGINEERING APPROACH TO TMJ DISORDERS One in four people are impacted by defects of the temporomandibular – or jaw – joint. Despite the pervasiveness of this affliction, treatments are lacking, and many sufferers resort to palliative measures to cope with the pain and debilitation it causes.

“The TMJ is central to chewing, talking and so many other daily activities, so when this crucial joint is impaired, there are significant negative effects on quality of life,” said Kyriacos A. Athanasiou, UCI Distinguished Professor of biomedical engineering.

“The problem may start with slight pain and clicking and get progressively worse to the point where it’s not just impacting the jaw but the entire body.”

Athanasiou is senior author on a paper published recently in the Cell Press journal Trends in Molecular Medicine that examines the causes of temporomandibular disorders, past failures in treating them and new approaches based on tissue-engineering innovations developed in his laboratory. Co-authors are Ryan Donahue, UCI graduate student researcher in biomedical engineering, and Jerry Hu, UCI principal development engineer in biomedical engineering.

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Temporomandibular disorders can be the result of sudden injuries or wear and tear over time. The cartilage disc between the mandible and the temporal bone is subject to thinning or perforation. The condition usually affects patients between the ages of 20 and 50. Most strikingly, premenopausal women are eight times more likely to experience jaw joint problems than men – which Athanasiou calls the TMJ gender paradox.

Typical treatments include physical therapy, splints and adjustments, corticosteroid injections and pain medications. Only about 5% of sufferers are candidates for surgical interventions. The TMJ is a joint like many others in the body, but surgeries to repair it are rare because of its location.

“It has to do with the proximity of the TMJ to the brain,” Athanasiou said. “Back in the 1980s, many patients – primarily women – came forward with issues they had with the TMJ. The solution at the time was to insert a spacer between the two bones articulated in the jaw.”

The spacer was made of Teflon, a material approved by the U.S. Food and Drug Administration.

“It turns out that Teflon was an absolute catastrophe for all of those women,” Athanasiou said. “Because of the large mechanical forces generated in the jaw, the Teflon broke up into pieces, and because of the proximity of the TMJ to the brain, those pieces somehow found their way into the brain.”

This fiasco set back therapies for temporomandibular disorders for decades, but now Athanasiou and his colleagues in UCI’s Department of Biomedical Engineering are working on new approaches that eschew synthetic materials entirely. They’re developing biological TMJ discs in the laboratory that will be suitable for implantation in humans.

“The end product that we aspire to use for treating afflictions of TMJ discs is a tissue-engineered product that’s fully alive, biological and mechanically comparable to the real thing,” Donahue said. “So even if it breaks down, it will be like any other biological component, without having pieces of foreign material entering the brain.”

UCI Department of Biomedical Engineering

NIH GRANT TO FUND NEW ELCACT INSTRUMENT This fall, a new state-of-the-art, highly sensitive microscope will be installed at UCI’s Edwards Lifesciences Center for Advanced Cardiovascular Technology (ELCACT), giving researchers the capability to expand and accelerate their research. The instrument is funded in part by a highly competitive S10 equipment grant from the National Institutes of Health’s Office of Research Infrastructure Programs. UCI’s Office of the Vice Chancellor for Research provided matching funds.

The $594,000 grant will fund an Olympus Fluoview FV3000 with MPM System, a multispectral, multiphoton laser scanning microscope.

The tool will open the door to new cardiovascular and tissue engineering possibilities at ELCACT, a center that seeks to better understand cardiovascular disease and tissue vascularization. “This will allow us to conduct research and science related to topics such as heart cell structure-function-force generation relationships, macrophage mechanobiology, and the mechanics of growing vessels into implanted medical devices,” said principal investigator Elliot Botvinick, ELCACT associate director and professor in the departments of biomedical engineering and surgery.

Securing the grant was a five-year team effort led by Botvinick, Associate Professor Anya Grosberg and ELCACT Assistant Director Ann Fain. The effort included many biomedical engineering faculty who will use the equipment, including Tim Downing, Christopher Hughes, Abe Lee, Zhongping Chen, Arash Kheradvar, Kerry Athanasiou and Wendy Liu. The new microscope will have confocal and two-photon imaging, and onstage incubation for longitudinal studies.

Some of these studies utilize environmentally sensitive tissues that cannot be transported out of the building without compromising the research. The new instrument will be housed adjacent to the center’s Core Tissue Culture Facility, opening avenues for research involving mechanically sensitive samples.

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DIGMAN RECOGNIZED WITH NSF EARLY CAREER AWARD Michelle Digman, associate professor of biomedical engineering, earned a National Science Foundation Faculty Early Career Development award. Digman will receive $500,000 for her project to develop an imaging platform with a fast-orbital tracking technique to follow mitochondria with nanometer precision and, at the same time, noninvasively measure metabolic changes at the local environment in cancer cells. “My lab is excited to continue to push the envelope in developing imaging technologies to noninvasively track mitochondrial recruitment and how environmental cues influence mitochondrial function within specific regions inside cancer cells, which may lead to aggressive cancer invasion.”

Among the NSF’s most prestigious, the CAREER award supports early career faculty who have the potential to serve as academic role models in research and education. Begun in 1995, the program provides recipients the opportunity to pursue outstanding research, excellence in teaching, and the integration of education and research.

BIOMEDICAL ENGINEERS DESIGN RAPID STD DETECTION DEVICE Samueli School biomedical engineers have developed a novel microfluidic platform capable of rapidly detecting multiple sexually transmitted viral infections. The technology uses blood or saliva samples and can diagnose HIV, HPV and HSV simultaneously in less than 20 minutes.

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The researchers used a five-step protein-array assay for the multiplexed detection of these viruses’ antibodies on an integrated microfluidic system.

Investigators say the technology can be adapted with different protein microarrays to detect a variety of other infections, such as dengue or chikungunya virus. The device could provide a promising approach for identification, analysis and monitoring of infectious disease, particularly in lowresource settings.

“This technology would allow clinicians to extend their ability to diagnose and start treatment in the field or at the bedside, providing point-ofcare services for viral infections,” said Neha Garg, lead investigator and a graduate student researcher in the lab of Abe Lee, professor of biomedical engineering and co-investigator.

NANOTECHNOLOGY TREATMENT SHOWS PROMISE AGAINST MULTIPLE SCLEROSIS A nanotechnology treatment derived from bone marrow stem cells has reversed multiple sclerosis symptoms in mice and could eventually be used to help humans, according to a new study led by UCI researchers.

“Until now, stem cell therapies for autoimmune and neurodegenerative diseases have produced mixed results in clinical trials, partly because we don’t know how the treatments work,” said corresponding author Weian Zhao, associate professor of pharmaceutical sciences and biomedical engineering, who is affiliated with the Sue & Bill Gross Stem Cell Research Center. “This study helps unravel that mystery and paves the way for testing with human patients.”

In past experiments, intravenously injected stem cells – taken from bone marrow and activated with interferon gamma, an immune system protein – often got trapped in filter organs before reaching their target.

For this study, published in the journal ACS Nano, researchers avoided that problem by extracting nanosized particles called exosomes from the stem cells and injecting them into rodents with MS. Loaded with anti-inflammatory and neuroprotective RNA and protein molecules, the exosomes were able to slip through the bloodspinal cord barrier. In addition to rejuvenating lost motor skills and decreasing nerve damage caused by MS, they normalized the subjects’ immune systems, something conventional drugs can’t do, said study colead author Reza Mohammadi, a UCI doctoral candidate in materials science and engineering.

More experiments are in the pipeline.

“This novel treatment will be tested on humans in early 2020, initially on people with Type 1 diabetes,” said co-lead author Milad Riazifar, who worked on the study as a pharmacological sciences doctoral student in Zhao’s lab and is currently helping prepare it for a City of Hope clinical trial. “If successful, it could pave the way for treating other autoimmune diseases.”

UCI Department of Biomedical Engineering

NSF GRANT SUPPORTS CENTER TO DEVELOP MICROFLUIDICS-BASED SOLUTIONS UC Irvine received phase 2 funding of $750,000 from the National Science Foundation to support the Center for Advanced Design and Manufacturing of Integrated Microfluidics (CADMIM).

The center, which launched five years ago, has two sites – one at UCI and another at the University of Illinois at Chicago.

CADMIM is an NSF Industry-University Cooperative Research Center, which fosters long-term partnerships among academia, industry and government in various technology sectors. Total phase 2 funding for the two-site center is $1.25 million over five years.

CADMIM focuses on developing miniature devices that can perform biochemical analytical functions quickly and cheaply. These chips have the potential to rapidly detect dangerous toxins in the blood, quickly screen hundreds of potential drugs, isolate cells for cancer diagnostics and treatment, or provide information on plant health that can improve crop outputs.

The UCI site has expertise in microfluidic sample preparation (cell and molecular sorting/separation, tissue dissociation, etc.), droplet-based microfluidics, autonomous microscale fluidic handling and various noninvasive detection methods.

“It is gratifying to know that the National Science Foundation is recognizing and rewarding the many accomplishments of CADMIM in its first five years, in research, technology transfer and most importantly, in building a community of students, faculty and industrial members that bridges advanced research with real-world applications,” said Abe Lee, CADMIM director and professor of biomedical engineering at the Samueli School.

CADMIM has worked with several industry leaders over the last five years, including Beckman Coulter, Corteva Agriscience, KWS, Monsanto, QIAGEN, ThermoFisher Scientific, Canon U.S. Life Sciences, Procter & Gamble, GSK, Genomics Institute of the Novartis Research Foundation, Douglas Scientific, Amgen Inc., Genentech Inc., Corning Inc., Los Alamos National Laboratories and Air Force Research Labs.

BME Discovery

CADMIM industry partners provide funding for university researchers to develop solutions for specific needs or problems.

UCI and UIC CADMIM researchers working with GSK, for example, are developing a human liver culture platform using induced pluripotent stem cell technology. These tools can screen thousands of compounds in early drug discovery using a sustainable and genetically diverse source of patient-specific cells. “Cell micropatterning is also being employed to organize the liver cultures precisely at the cellular scale, allowing for optimization of liver function and rapid identification and assessment of each cultured cell type by automated microscopy,” added investigator Elliot Hui, assistant professor of biomedical engineering at the Samueli School.

Jered Haun, Michelle Khine and Michelle Digman from UCI, and Salman Khetani, David Eddington and Jie Xu from UIC, are other key researchers at CADMIM.

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NEW STUDY EXAMINES BLOOD FLOW LEAKAGE AFTER TRANSCATHETER HEART VALVE REPLACEMENT For people with heart disease, particularly aortic valve stenosis, valve replacement is the primary treatment option. A narrowing of the valve opening, aortic valve stenosis restricts blood flow from the heart to the rest of the body. Since 2011, when the FDA first approved it, transcatheter aortic valve replacement (TAVR) has been a less invasive choice than traditional open-heart surgery for patients at high surgical risk.

However, a tiny gap can occur between the patient’s natural heart valve and the implanted valve after TVAR. Called paravalvular leak, or PVL, this gap leads to blood flow leakage from the aorta back into the heart’s left ventricle (regurgitation).

Although mild PVL is usually not serious, moderate PVL may lead to symptoms of heart failure, including fatigue and difficulty in breathing, among other complications. Moderate to severe regurgitation after TAVR has a poor prognosis and is associated with higher mortality.

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In a study published last fall in Nature’s Scientific Reports, UCI’s Arash Kheradvar and his team found that PVL leads to formation of an abnormal swirling pattern (vortex) in the heart’s left ventricle that clearly interferes with natural blood flow from the left atrium into the left ventricle. This negatively affects blood flow dynamics, including circulation, impulse and kinetic energy.

Using echocardiographic particle image velocimetry, an advanced method to measure the heart’s blood flow velocity based on echocardiography, the researchers were able to observe and study various fluid dynamic events that occur inside the heart relative to the location of the leak.

The study’s results emphasize the significance of the PVL location. “Our in vitro and in vivo studies show that posterior PVL is significantly more harmful than anterior PVL considering the blood flow dynamics inside the heart. According to those results, we predict that presence of posterior PVL may lead to worse patient survival and outcomes compared to anterior PVL and no PVL,” said Kheradvar, professor of biomedical engineering.

Accordingly, Kheradvar suggests more careful follow-up after TAVR, and if needed, early therapeutic interventions that may include PVL repair.

Kheradvar also has published a new book, Principles of Heart Valve Engineering, available through Academic Press, a division of global publisher Elsevier.

Directed at biomedical engineers, cardiologists, cardiothoracic surgeons, academics and other scientists and engineers, the book focuses on the current state of the art in heart valve science and engineering, therapies, and pathways to developing safer and more durable heart valve devices in the future. It is an interdisciplinary, comprehensive resource for heart valve engineering.

According to Kheradvar, who is also a medical doctor, since the inception of heart valve engineering in 1960s, the field lacked an all-inclusive resource of up-to-date heart valve research and development efforts. He compiled a group of internationally known researchers in the field from more than 15 institutions, including bioengineers and cardiologists, to contribute. The result is a comprehensive textbook covering a wide range of topics, including heart valve anatomy, embryology, mechanobiology, epidemiology, surgery, tissue engineering, computer modeling and more.

UCI Department of Biomedical Engineering

LIU CO-AUTHORS GUIDE FOR FEDERAL INVESTING IN SYNTHETIC BIOLOGY RESEARCH Chang Liu is among a group of more than 80 scientists and engineers from 30 universities and a dozen companies who released a road map to guide and encourage government agencies to invest effectively in engineering and synthetic biology research endeavors.

BIOMEDICAL ENGINEERS DEVELOP WEARABLE RESPIRATION MONITOR WITH CHILDREN’S TOY Samueli School biomedical engineers have developed a wearable, disposable respiration monitor that provides high-fidelity readings on a continuous basis. Designed to help children with asthma and cystic fibrosis and those with chronic pulmonary conditions, the inexpensively produced sensors were created using the popular children’s toy Shrinky Dinks, thin sheets of plastic that are painted or drawn on and then shrunk with heat.

Placed in two positions – one between the ninth and 10th ribs and another on the abdomen – the Band-Aid-like devices track the rate and volume of the wearer’s respiration by measuring the local strain on the application areas. The information gleaned could, in the case of asthma, help warn of an oncoming attack.

The devices are made by applying a very thin layer of metal to a sheet of the plastic toy and then heatshrinking it to cause corrugation. The film is then transferred to a soft, stretchy material – similar to a small bandage – that can be adhered to a patient.

Signals from embedded sensors can be transmitted via Bluetooth to be displayed on a smartphone app.

The lab of Michelle Khine, where the devices were developed, is well-known for employing Shrinky Dinks as a platform for medical applications. About a decade ago, Khine innovated the use of the toy to produce microfluidic devices. “It’s amazing that this toy for kids has enabled us to create these robust sensors that may one day benefit children and others around the world,” she said.

The new technology has been tested on healthy subjects, and plans are underway for a pilot trial with a small number of asthma sufferers.

BME Discovery

Liu, assistant professor of biomedical engineering, is lead author of the document’s biomolecular engineering section. The Engineering Biology Research Consortium, partially funded by the National Science Foundation and headquartered at UC Berkeley, produced the treatise to not only improve public health, food crops and the environment, but also fuel the economy and maintain U.S. leadership in synthetic biology. Current efforts in the field include genetic modification of crops; microbe engineering to produce drugs, fragrances and biofuels; gene editing and human gene therapy. But the future will bring even more complex applications.

The document’s authors outline synthetic biology’s challenges and opportunities to help decision-makers determine whether to make it a research priority for the U.S. “The road map is backed by rich technical analysis and projections to focus our nation’s goals in engineering biology in a concrete manner,” Liu said. “I was impressed by the open and inclusive process that informed this project.

We actively sought and incorporated the contributions, expertise and ideas of scores of researchers in the greater synthetic biology community, including postdocs and graduate student trainees who will define the future of our field.”

HAUN RECEIVES PILOT STUDIES FUNDING Jered Haun received a 2019 Pilot Studies Award from the UCI Institute for Clinical and Translational Science.

The $25,000 award supports Haun’s efforts to develop a microfluidic device platform for processing human fat for autologous therapies.

“Fat tissue contains a large number of stem cells that could readily be collected and used to heal wounds and treat diseases,” said Haun, assistant professor of biomedical engineering. “Funds from this award will help us develop and test new microfluidic device components that will make it possible to fully automate the processing of fat into a stem-cell-based therapeutic, paving the way to clinical applications.”

The ICTS Pilot Studies Award is designed specifically to support exceptionally innovative and/or unconventional research projects that have the potential to create or overturn fundamental paradigms.

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FEATURE

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UCI Department of Biomedical Engineering

REWIRING THE BRAIN

Rehabilitative tool could mitigate the effects of stroke ANNA LYNN SPITZER

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ORE THAN 7 MILLION PEOPLE IN THE U.S. ALONE ARE STROKE SURVIVORS. Stroke can leave its victims with ongoing deficits, including one known as foot drop, which affects up to 60% of those who have suffered a stroke. The patient cannot lift his/her foot toward the ankle completely – a process called dorsiflexion – which results in a compromised gait. Two Samueli School researchers are part of a team that is developing a rehabilitative tool that they think can help patients reestablish important brain-muscle connections and relearn proper dorsiflexion.

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The team includes biomedical engineering professor and department chair Zoran Nenadic and David Reinkensmeyer, professor of biomedical engineering, mechanical & aerospace engineering and anatomy & neurobiology; and clinical neurologists Dr. Steven Cramer and Dr. An Do, who leads the effort. The researchers received a five-year, $3.8 million grant from the National Institutes of Health to investigate the effectiveness of their electroencephalography (EEG) brain-computer interface and functional muscle stimulator.

“Dorsiflexion is a necessary movement to walk normally and not drag your foot,” says Nenadic. “It seems like a minor inconvenience but it’s actually a fundamental part of the gait cycle and it affects patients’ lives significantly. Years of research have failed to solve this problem.”

The device includes an electrodeladen elastic cap, an amplifier that magnifies brain signals and sends

them from patient to computer, and a functional electrical stimulator, which attaches to the patient’s tibialis anterior (shin) muscles. Electrodes in the cap capture and send brain waves through the amplifier and into the computer as the patient, who is watching the computer screen for prompts, tries to dorsiflex.

Algorithms recognize the specific brain waves tied to dorsiflexion, and as the patient attempts this movement, the device sends electric signals to his/her leg muscles.

That direct stimulation causes the patient’s foot to dorsiflex. It also sends an electrochemical signal called an action potential back to the spinal cord, where the signal meets the patient’s brain wave signals.

This meeting and activation of the peripheral nervous system with the central nervous system can lead to positive outcomes, says Nenadic.

He and Reinkensmeyer believe that simultaneously activating the brain and nervous system can lead to a “rewiring” at the spinal cord and/or motor cortex level, and they are optimistic that this can inspire the brain to reestablish the missing connections. “It’s well known in neuroscience that when you have two action potentials coincident at a connection, it makes the connection stronger,” says Reinkensmeyer.

A prototype of the device was developed in 2015 for a previous study, which found it safe for rehabilitative use. Now, researchers plan to miniaturize the device and conduct a clinical trial with stroke patients that compares the device’s efficacy to that of traditional physical therapy and later, robotic therapy.

“One of the scientific questions we’re trying to answer is ‘do you need electrical stimulation of the muscle?’

UCI Department of Biomedical Engineering

which a robot does not provide,” says Reinkensmeyer, who has previously developed hand and arm robots.

“We’re really interested in learning whether that sensory information coming back to the nervous system from your limb really matters. There’s a really big part of the brain dedicated to sensation for the hand, so it will be interesting to see if the same principles apply to the foot.”

If there is improvement in dorsiflexion, researchers want to better understand the reasons.

Reinkensmeyer says improvement could be caused by plasticity in the spinal cord resulting from the action potential flowing backward from the muscle, or it could be the result of brain plasticity caused by the sensory simulation of the muscles themselves. They hope to be able

BME Discovery

to “tease apart the mechanisms of improvement,” says Nenadic.

In the clinical study, researchers will measure patients’ dorsiflexion abilities before, during and after the patients have used the device several times a week for about a month.

Patients’ abilities will be measured again three months later.

One goal of the study is to determine which patients will benefit most from the device.

Researchers will compare certain stroke features and measurements before therapy begins to see if they can predict which variables will indicate success.

“If we are successful,” says Nenadic, “patients could have improved ability to walk after stroke, which will increase the social reintegration of this patient population.”

If we are “ successful,

patients could have

improved ability to walk after stroke.”

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STUDENTS

RECOGNITION AND REWARD Prestigious fellowships will further graduate research

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TWO BIOMEDICAL ENGINEERING STUDENTS HAVE RECEIVED GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP) AWARDS FROM THE NATIONAL SCIENCE FOUNDATION. The GRFP is a competitive program that recognizes and supports outstanding students who are pursuing research-based graduate degrees in science and engineering. Courtney Kay Carlson and Kimmai Phan are among 24 GRFP awardees from UCI who will receive three years of annual funding.

Carlson, who is earning a doctorate, works to engineer mammalian cells that will be able to record their own developmental history as they proliferate within living tissue. “There are many exciting applications for these engineered cells,” said Carlson, who is advised by Assistant Professor Chang Liu. The cells could benefit developmental biologists trying to understand complex multicellular organisms and be useful for clinical studies trying to uncover the causes of developmental disorders, congenital heart disease or cancer progression.

Carlson also won a two-year fellowship from the American Heart Association.

She will receive $53,000 from the AHA in support of her research.

Phan, who graduated last spring with a bachelor’s degree in biomedical engineering and a minor in materials science and engineering, worked in the lab of her adviser, Assistant Professor Tim Downing.

Her project, in collaboration with Associate Professor Anna Grosberg, sought to determine whether DNA methylation, an important epigenetic mechanism, plays a role in the topography-mediated maturity of cardiac muscle cells. “Being the daughter of parents with chronic diseases, I’ve always been interested in the intersection of medicine and engineering therapies to combat illnesses,” said Phan.

“Understanding fundamentally how tissues and disease function at the gene expression level is so powerful as a tool to improve patient care and medicine.”

UCI Department of Biomedical Engineering

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TWO BIOMEDICAL ENGINEERING GRADUATE STUDENTS WITH THE SAME ADVISER WON NATIONAL AWARDS LAST YEAR. Erik GonzalezLeon was named a 2018 Howard Hughes Medical Institute Gilliam Fellow and Evelia Salinas won the 2018 Career Development Award from the Biomedical Engineering Society. Both are doctoral students who work in the lab of UC Irvine Distinguished Professor Kyriacos Athanasiou.

Gonzalez-Leon uses self-assembling methods to tissue engineer the meniscus, the thin fibrous cartilage between the surfaces of joints. He adds biochemical stimuli during tissue culturing to enhance the meniscus’s mechanical properties in an effort to bring it closer to native tissue.

Gonzalez-Leon and Athanasiou will receive $50,000 a year – including a stipend, a training allowance and an institutional allowance – for up to three years while Gonzalez-Leon completes his doctorate.

“I am excited to be a representative of the HHMI Gilliam Fellowship, and I look forward to doing my part in advancing diversity in the sciences,” GonzalezLeon said. “This fellowship will allow BME Discovery

me to focus not only on my own scientific endeavors, but also provides a platform for me to spark interest in the sciences among underrepresented groups.”

Like Gonzalez-Leon, Salinas tissueengineers cartilage found in the body’s joints, using different models of simulation to drive the engineered cartilage to behave more like the body’s cartilage.

The BMES Career Development Award supports travel to the society’s annual meeting for underrepresented graduate students, postdoctoral fellows, early career faculty and early career professionals from underrepresented populations in biomedical engineering. Salinas received complimentary registration and a travel stipend to the October meeting in Atlanta, Georgia. “I am very pleased to have won this Career Development Award from BMES,” Salinas said. “To be recognized by BMES is truly an honor.”

Salinas and Gonzalez-Leon’s adviser, Athanasiou, was understandably pleased with his students. “Both of these students are outstanding and a pleasure to have in our department. We are so lucky to be surrounded by excellence,” he said.

BIOMEDICAL ENGINEERING DOCTORAL STUDENT RACHEL SMITH WON A 2018-19 GRADUATE DEAN’S DISSERTATION FELLOWSHIP AWARD FROM THE UCI GRADUATE DIVISION. The award, designated for students in their final year of graduate education, allows them to forgo non-research related employment and concentrate on completing their dissertation. Smith conducts computational analysis of brain signals in patients with epilepsy, specifically studying infantile spasms, a potentially devastating form of epilepsy that strikes within the first year of life. She is developing quantitative tools to assess how the infants’ brains are functioning differently from the brains of healthy babies, as well as building models to predict which patients are going to respond to treatment. “We hope that this will expedite the treatment process and improve patients’ long-term outcomes,” said Smith, who is advised by Beth Lopour, assistant professor.

FEATURE

JOURNEY TO LAB-ON-A-CHIP

Professor takes research into the marketplace JACKIE CONNER

STEVE ZYLIUS

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UCI Department of Biomedical Engineering

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BRAHAM LEE IS NO STRANGER TO PURSUINGAMBITIOUS RESEARCH. The UC Irvine biomedical engineering professor has over 40 issued patents – several of which have been licensed to major corporations – and he is director of the Center for Advanced Design and Manufacturing of Integrated Microfluidics and outgoing chair of the Department of Biomedical Engineering.

Lee’s efforts to solve problems linked to neurodegenerative diseases and pharmaceutical efficacy all stem back to microfluidics and his early ability to combine engineering and biological systems. Through collaborations on and off campus, Lee, who arrived at UCI in 2001, helped grow everything big and small, from the biomedical engineering program, to several startup ventures, to developing tiny organs to help advance drug development and precision medicine.

Originally trained as a mechanical engineer with a doctorate focusing on microelectromechanical systems, Lee developed clinical tools to treat stroke at the Lawrence Livermore National Lab (LLNL) from 1992 until 1999.

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This led him toward a field that, at the time, was brand new: biomedical engineering.

“It was an exciting time for national labs in general to spin off technology to the commercial or private sectors,” he says. “It was a new era.”

After leaving LLNL, Lee spent three years at the Defense Advanced Research Projects Agency (DARPA), where he worked as a program manager in the Micro Technology Office. He established and developed a $60 million program coined Biofluidic Chips or “BioFlips,” which incorporated the principles and technologies of mechanical engineering into living systems. “I realized you need to deal with fluids in the devices we developed because the body is primarily water, and I also realized it’s not just the doctors that need to get down to the biology,” he says.

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The program’s goal was to develop a physiological status-monitoring system for troops to track their wellbeing and combat preparedness. Eventually, he worked with generals to develop this system as a form of national security and defense.

Then, he began thinking about diagnostics and treatments for use in conjunction with the Human Genome Project, an international scientific effort that mapped the entire human genome.

“We were starting to get to the core of the few molecules or cells or bad pathogens that were triggering this whole thing,” said Lee. “People refer to it today as precision medicine. That was the stage where I think a lot of these technologies were starting to form.”

During a short stint at the National Cancer Institute, Lee learned more about

the biology of cancer, and although he had planned to go back to LLNL, he came to UCI instead. “That experience made me feel that I really wanted to be the one involved in the projects, instead of managing a portfolio of projects,” says Lee. “So I applied for a faculty position.”

After moving to Irvine, Lee discovered a potential collaboration with fellow faculty and neighbor Lisa Flanagan, associate professor of neurology. Discussions with Flanagan about a microfluidic pump he had developed at LLNL led the two to discover that the technology was applicable to her research, which required ways to enrich and sort neural stem cells for treating neurodegenerative diseases.

By separating the cells, Lee and Flanagan were able to better identify stem cells by their individual electrical signatures. Flanagan is continuing this research, with the ultimate goal of treating neurodegenerative diseases such as Alzheimer’s and Parkinson’s. The coincidental collaboration fostered 10 years of research, publications and patents.

UCI’s biomedical engineering center expanded into a department in 2002. Lee and a few other faculty members helped grow the small-but-mighty curriculum, which later became one of UCI’s most popular majors.

“There was a lot of interest and excitement because Irvine is home to a large number of biomedical device companies,” Lee says. “There’s a need for a strong biomedical engineering program here to build out an ecosystem of innovative research, and to educate and train future employees.”

UCI Department of Biomedical Engineering

Microfluidics, in particular, took hold and has since branched out into multiple research endeavors and collaborative organizations on campus. One of those, the Center for Advanced Design and Manufacturing of Integrated Microfluidics, moves microfluidics and other technologies from university laboratories toward industry and commercial applications.

Just over two years ago, Lee, along with molecular biology and biochemistry Professor Chris Hughes and Steve George, professor and chair of biomedical engineering at UC Davis, co-founded Kino Biosciences, now known as Aracari. The startup seeks to create tools that sharpen and revolutionize drug discovery and development, with a long-term goal of creating personalized medicine platforms and databases.

The palm-sized technology, often referred to as a “lab-on-a-chip,” incorporates a proprietary vascularized micro-organ (VMO) device that recreates complex 3D cellular structures in which oxygen and nutrients are transported through formed blood vessels. The cells that build the VMOs currently are harvested from cord blood, but efforts are in place to harvest a patient’s own stem cells.

So far, the company’s device can recreate 16 VMOs, including heart, liver, pancreas and brain to help speed up drug discovery and save money on personalized medicine.

The startup also developed vascularized micro-tumors (VMT), which are used to recreate tumor cell types. With VMTs, a pharmaceutical company could test the toxicity of a drug and a drug’s interactions with healthy tissues and other body parts.

BME Discovery

“This will be a platform where pharma can quickly say, ‘I can check this off, check that off’: toxicity, efficacy and other types of side effects,” says Lee, who received a Proofof-Product grant for Aracari in addition to a $250,000 Small Business Innovation Research grant.

Looking ahead, Lee and the Aracari team will continue to develop their platform as well as a clientele base that includes top pharma companies.

“Our platform is unique and powerful compared to the competition. We’re trying to promote and market this to the pharma companies so they realize what we can do for them,” Lee says. “They’ll start to see this as a powerful way to predict if their drugs are good or bad.”

Additionally, he hopes to raise more capital to increase the staff so the team can start to develop other personalized medicine platforms. Lee plans to work with hospitals to help doctors decide the best drug for their patients.

“I continue to enjoy fundamental research and publishing our results to push the forefront of technology,” he says. “Now, I feel like I don’t have to publish for the sake of publishing … rather, if I can make a difference in getting a technology that can help a lot of people out of the lab, that motivates me all the more.”

“Our platform is unique and powerful compared to the competition.”

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ACCOLADES LEE ELECTED FELLOW OF BMES AND NATIONAL ACADEMY OF INVENTORS Abe Lee, biomedical engineering professor and outgoing department chair, was elected last year to both the Biomedical Engineering Society 2018 Class of Fellows and as a fellow of the National Academy of Inventors. BMES, the professional society for biomedical engineering and bioengineering has more than 7,000 members; Lee was one of 21 selected last year by his peers to receive the honor. The NAI designation is the highest professional distinction accorded solely to academic inventors who have demonstrated a prolific spirit of innovation in originating or facilitating outstanding inventions that have had a tangible impact on quality of life, economic development and the welfare of society. Lee is the ninth NAI fellow from UCI. “I am humbled to be recognized for what I love to do and am passionate about,” said Lee.

GRATTON NAMED AIMBE FELLOW

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A UCI biomedical engineering professor is among 157 medical and biological engineers inducted this year into the College of Fellows of the American Institute for Medical and Biological Engineering (AIMBE). Enrico Gratton joined the College of Fellows class of 2019 at a ceremony held in March during the AIMBE Annual Meeting at the National Academy of Sciences in Washington, D.C. Election to the College of Fellows is a prestigious professional distinction; fellows, who are recognized for outstanding achievement, represent the top two percent of medical and biological engineers from around the world.

Gratton, professor of biomedical engineering, was elected “for seminal, outstanding contributions to the fields of fluorescence spectroscopy and imaging to study structure and function of biomolecules.” The founder and principal investigator of UCI’s Laboratory for Fluorescence Dynamics, the country’s only national research center dedicated to fluorescence, Gratton also has joint appointments in physics and astronomy, and surgery. His research focuses on biomedical fluorescence spectroscopy, including measurements and microscopy; and designing, testing and implementing fluorescence hardware, software and biomedical applications.

These techniques can probe the structure and function of biomolecules and membranes, and track biological processes in cell and tissue cultures.

ATHANASIOU APPOINTED NEW SAMUELI ENDOWED CHAIR IN ENGINEERING UCI Chancellor Howard Gillman appointed biomedical engineering Distinguished Professor Kyriacos A. Athanasiou to a Henry Samueli Endowed Chair in Engineering. Established in 2005 by the UC Regents, with funding from Henry and Susan F. Samueli, the endowed chair positions were created in support of engineering programs and other related disciplines within the Samueli School. This chair is the first in the department.

Athanasiou researches musculoskeletal and cartilaginous tissues and develops clinical instruments and devices. The senior academic has spent his career inventing biomimetic tissue for treating damaged knees, jaws, hips, shoulders and other joints. Along the way, Athanasiou has become an authority on translating engineering innovations into commercially available medical treatments. He is a recipient of the American Society of Mechanical Engineers 2018 Savio L-Y. Woo Translational Biomechanics Medal and a past president of the Biomedical Engineering Society.

“Some of our best schools and programs, emerging colleges and great buildings at UCI carry the Samueli name,” said Athanasiou.

“Inasmuch as I equate the Samuelis with excellence, it is such an honor for me to be named a recipient of the Henry Samueli Chair.

I look forward to even greater accomplishments in translating our engineering advances to medical use.”

UCI Department of Biomedical Engineering

LIU HONORED WITH YOUNG INNOVATOR AWARD Chang Liu has received the 2019 Young Innovator Award from the American Chemistry Society’s Synthetic Biology journal. The recognition honors the contributions of a young scientist who has made a major impact on synthetic biology and/or related fields. Liu, assistant professor of biomedical engineering, conducts research in the fields of synthetic biology, chemical biology and directed evolution. He is particularly interested in engineering specialized genetic systems for rapid mutation and evolution to address problems ranging from protein engineering to developmental biology.

Liu has been recognized with a number of awards, including the Sloan Research Fellowship, the NIH New Innovator Award, the Beckman Young Investigator Award and the Dupont Young Professor Award. “The synthetic biology community is an extraordinary one, full of amazing scientists and engineers who have an ambitious vision for the future of bioengineering,” said Liu. “I am lucky to be a part of that group and honored to be recognized by them. I am also deeply thankful for the wonderful scientists in my lab, whose creativity, dedication and kindness make our research possible and make me love what we do.”

COLLABORATION LEADS TO SPECIAL INVITATION Samueli School professor Tibor Juhasz (left) attended the 2018 Nobel Prize ceremony in Stockholm, Sweden, where he watched his longtime collaborator Gerard Mourou win one of the Nobel Prizes in physics. Because his own research is so closely intertwined with that of Mourou, Juhasz received an invitation to both the Nobel ceremony and the four days of events surrounding it, including lectures, discussions, receptions, parties and a banquet with the Swedish king and royal family. Juhasz began working with Mourou in January 1987, when Juhasz joined Mourou’s lab at University of Rochester as a postdoctoral researcher.

The two collaborated for years on chirped pulse amplification (CPA) lasers and the development of an ophthalmic femtosecond laser; Mourou is on the board of Juhasz’s startup company, ViaLase, a UCI spinoff that is developing new applications to treat anterior chamber disorders of the eye with the femtosecond laser.

“Gerard truly deserved this award, not only for his groundbreaking invention of CPA ... but also for his magnificent contribution to the optics community − from educating many excellent scientists to his visionary role in the establishment of numerous high-power laser research centers all around the word,” said Juhasz.

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BIOMEDICAL ENGINEERING TEAM PLACES IN BUSINESS PLAN COMPETITION A biomedical engineering team led by graduate student Ning Ma won second place in its semifinal round at the 2019 Rice University Business Plan Competition. The proposed company, called Embryologic, has developed a noninvasive imaging device that can assess the quality of an embryo for in vitro fertilization.

The UCI team was one of 42 competitors and one of 15 semifinalists. The Rice Business Plan Competition is a graduate-level student startup competition designed to give collegiate entrepreneurs a real-world experience to fine-tune their business plans and elevator pitches and to generate funding and successfully commercialize their product.

Embryologic’s device uses fluorescence lifetime imaging microscopy to measure intrinsic fluorescent signals from pre-implantation embryos. The team discovered that embryos have unique fluorescence lifetime signatures that change as they develop in each stage of division.

The embryos also have unique signatures when they become unhealthy. Embryologic can assesses the developmental potential of pre-implantation embryos to increase the success rate of IVF and decrease the financial and emotional costs for couples.

Ma is a graduate student in the lab of Michelle Digman, biomedical engineering associate professor. “We have developed a machine learning algorithm called the embryo viability index to select the best embryo with the highest developmental potential,” said Ma. “We hope to bring safety and confidence to future parents going through in vitro fertilization.”

ALUMNI

Diabetic Support

HUMBLE Technologies administers a much-needed dose of innovation

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S A TEENAGER HELPING TO CARE FOR HIS DIABETIC GRANDFATHER, BIOMEDICAL ENGINEERING ALUMNUS BIEN GUTIERREZ LEARNED FIRSTHAND THAT THE SYRINGES USED TO ADMINISTER INSULIN COULD BE MORE USER-FRIENDLY. That experience led him to establish HUMBLE Technologies with co-founders Wendy Nguyen, Krissa Tassin, Chad Bishop and Xiantong Yang. The company’s unique design allows syringe users to ensure proper dosing, purge air bubbles and prime injections more easily than by using traditional syringes.

BASED ON AN ARTICLE BY ETHAN PEREZ, UCI BEALL APPLIED INNOVATION

UCI Department of Biomedical Engineering

“I felt that knowing what I know,maybe I can help.”

According to a recent report from the Centers for Disease Control and Prevention, there are roughly 2 million Americans living with Type 1 diabetes, which requires daily injections of insulin.

HUMBLE Technologies seeks to reduce risk to patients and alleviate the fear associated with those injections.

“The experience of being a 14-year-old and not having anywhere to turn to for help – I think that story happens a lot more often in the real world than people may think,

especially in low-income neighborhoods,” said Gutierrez, the company’s CEO. “I felt that knowing what I know, maybe I can help.”

But work on the HUMBLE syringe did not begin right away. Gutierrez first shared his idea for the syringe when he and Nguyen, who is now HUMBLE Technologies chief operating officer, were undergraduates. Neither was interested in the projects available in their senior biomedical engineering design class, so Nguyen pushed Gutierrez to develop his own idea.

“Instead of spending time working on someone else’s project, why don’t

you work on that?” said Nguyen, recalling her conversation with Gutierrez.

Since then, the startup has participated in several entrepreneurship programs and has placed in numerous competitions, including the Samueli School’s Beall Student Design Competition. HUMBLE Technologies is continuing to develop its intellectual property and has its sights set on FDA 510(k) approval.

The company is not stopping at syringes, however; it aims to position itself as an innovator of medical tools and devices that need upgrades to better meet the needs of an ever-changing health care landscape.

“The big message I want to send out there about my product is this: Someone out there is thinking about health care transitions and support is coming,” said Gutierrez.

Traditional syringes, like the one pictured, can intimidate those with diabetes, causing them not to comply with their medication schedules. The founders of HUMBLE Technologies are developing an alternative that reduces patient risks and helps alleviate user fears.

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DIRECTORY Zoran Nenadic, D.Sc.

James Brody, Ph.D.

William J. Link Chair and Professor of Biomedical Engineering.

Associate Professor of Biomedical Engineering;

Zhongping Chen, Ph.D. Professor of Biomedical Engineering; Surgery

Kyriacos Athanasiou, Ph.D.

Research Interests: biomedical optics, in vivo optical imaging, microvasculature, light-based therapeutics

Gregory J. Brewer, Ph.D. Adjunct Professor of Biomedical Engineering

Research Interests: neuronal networks, decoding brain learning and memory, brain-inspired computing, Alzheimer’s disease, brain aging, neuron cell culture

Email: egratton@uci.edu

Anna Grosberg, Ph.D.

Email: choib@uci.edu

Associate Professor of Biomedical Engineering; Chemical and Biomolecular Engineering

Michelle Digman, Ph.D.

Arnold and Mabel Beckman Chair in Laser Biomedicine and Professor of Surgery; Biomedical Engineering; Developmental and Cell Biology

Email: elliot.botvinick@uci.edu

Research Interests: design of new fluorescence instruments, protein dynamics, single molecule, fluorescence microscopy, photon migration in tissues

Professor of Surgery; Biomedical Engineering

Michael Berns, Ph.D.

Research Interests: laser microbeams, cellular mechanotransduction, mechanobiology

Professor of Biomedical Engineering; Physics and Astronomy

Bernard Choi, Ph.D.

Email: athens@uci.edu

Professor of Surgery; Biomedical Engineering

Enrico Gratton, Ph.D.

Email: z2chen@uci.edu

Research Interests: understanding and enhancing the healing processes of musculoskeletal tissues as well as the body’s cartilaginous tissues; applying the translation of engineering innovations to clinical use, especially in terms of instruments and devices

Elliot Botvinick, Ph.D.

Email: adurkin@uci.edu

Research Interests: biomedical optics, optical coherence tomography, bioMEMS, biomedical devices

Distinguished Professor of Biomedical Engineering

Email: mwberns@uci.edu

Research Interests: spatial frequency domain imaging, wide-field functional imaging, quantitative near-infrared spectroscopy of superficial tissues, chemometrics, fluorescence spectroscopy, quantitative spectral imaging

Email: jpbrody@uci.edu

Email: znenadic@uci.edu

Research Interests: photomedicine, laser microscopy, biomedical devices

Associate Professor of Biomedical Engineering

Research Interests: bioinformatics, micro-nanoscale systems

Research Interests: adaptive biomedical signal processing, control algorithms for biomedical devices, brain-machine interfaces, modeling and analysis of biological neural networks

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Anthony Durkin, Ph.D.

Research Interests: computational modeling of biological systems, biomechanics, cardiac tissue engineering

Associate Professor of Biomedical Engineering NEWLY PROMOTED

Email: grosberg@uci.edu

Research Interests: biophotonics, fluorescence spectroscopy and microscopy, nanoscale imaging, mechanotransduction, cancer cell migration, fluorescence lifetime and metabolic mapping

Jered Haun, Ph.D. Associate Professor of Biomedical Engineering, Chemical and Biomolecular Engineering, Materials Science and Engineering

Email: mdigman@uci.edu

Tim Downing, Ph.D. Assistant Professor of Biomedical Engineering, Microbiology & Molecular Genetics

Research Interests: stem cell and tissue engineering, regenerative biology, cell reprogramming, epigenomics, mechanobiology Email: tim.downing@uci.edu

NEWLY PROMOTED

Research Interests: nanotechnology, molecular engineering, computational simulations, targeted drug delivery, clinical cancer detection Email: jered.haun@uci.edu

Elliot E. Hui, Ph.D. Associate Professor of Biomedical Engineering

Research Interests: microscale tissue engineering, bioMEMS, cell-cell interactions, global health diagnostics Email: eehui@uci.edu

Email: gjbrewer@uci.edu

UCI Department of Biomedical Engineering

Tibor Juhasz, Ph.D.

Abraham P. Lee, Ph.D.

Daryl Preece, Ph.D.

Professor of Ophthalmology; Biomedical Engineering

Professor of Biomedical Engineering; Mechanical and Aerospace Engineering

Assistant Professor of Biomedical Engineering

Research Interests: laser-tissue interactions, high-precision microsurgery with lasers, laser applications in ophthalmology, corneal biomechanics Email: tjuhasz@uci.edu

Arash Kheradvar, M.D. , Ph.D. Professor of Biomedical Engineering; Mechanical and Aerospace Engineering Research Interests: cardiac mechanics, cardiovascular devices, cardiac imaging Email: arashkh@uci.edu

Research Interests: lab-ona-chip health monitoring instruments, drug delivery micro/nanoparticles, integrated cell-sorting microdevices, lipid vesicles as carriers for cells and biomolecules, high-throughput droplet bioassays, microfluidic tactile sensors Email: aplee@uci.edu

Chang C. Liu, Ph.D. Assistant Professor of Biomedical Engineering, Molecular Biology and Biochemistry

Michelle Khine, Ph.D.

Research Interests: genetic engineering, directed evolution, synthetic biology, chemical biology

Professor of Biomedical Engineering, Materials Science and Engineering

Wendy F. Liu, Ph.D.

Research Interests: development of novel nano- and microfabrication technologies and systems for single cell analysis, stem cell research, in vitro diagnostics Email: mkhine@uci.edu

Christine King, Ph.D. Assistant Professor of Teaching Biomedical Engineering

Research Interests: engineering and STEM education, active learning, wireless health systems, rehabilitation, brain-computer interfaces, robotics Email: kingce@uci.edu

Frithjof Kruggel, M.D. Professor of Biomedical Engineering

Research Interests: biomedical signal and image processing, anatomical and functional neuroimaging in humans, structure-function relationship in the human brain Email: fkruggel@uci.edu

Email: ccl@uci.edu

Email: dpreece@uci.edu

William C. Tang, Ph.D. Professor of Biomedical Engineering, Chemical and Biomolecular Engineering

Research Interests: micro-electro-mechanical systems (MEMS) nanoscale engineering for biomedical applications, microsystems integration, microimplants, microbiomechanics, microfluidics Email: wctang@uci.edu

Associate Professor of Biomedical Engineering; Chemical and Biomolecular Engineering

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Research Interests: biomaterials, microdevices in cardiovascular engineering, cell-cell and cellmicro-environment interactions, cell functions and controls Email: wendy.liu@uci.edu

Beth A. Lopour, Ph.D. Assistant Professor of Biomedical Engineering

Research Interests: computational neuroscience, signal processing, mathematical modeling, epilepsy, translational research Email: beth.lopour@uci.edu

Joshua Mauney, Ph.D. Associate Professor of Biomedical Engineering; Urology

Research Interests: tissue engineering of urogenital, gastrointestinal, and respiratory hollow organs; silk fibroin NEW FACULTY biomaterials, cellular and molecular mechanisms of tissue MEMBER regeneration following surgical reconstruction Email: mauneyj@uci.edu

BME Discovery

Research Interests: nano-optics, neuro-photonics, optical forces and mechanotransduction, singular optics and biophotonics

Welcome Ronke Olabisi The Department of Biomedical Engineering welcomes Ronke Olabisi to the faculty.The assistant professor, from Rutgers University, will join the Samueli School this winter. Her research interests encompass biomechanics, biomaterials, tissue engineering and regenerative medicine to repair or build de novo tissues for treating defects due to injury, disease, aging or spaceflight. Olabisi studied aerospace engineering at MIT, moved to University of Michigan for her master’s research in mechanical and aerospace engineering and to University of WisconsinMadison for her doctorate in biomedical engineering. She is the recipient of an Engineering Information Foundation Award (2016), NSF CAREER Award (2018) and a Johnson & Johnson Women in STEM2D Scholar Award (2019). She is a member of 100 Year Starship, an interdisciplinary initiative that is exploring the possibility of human interstellar travel, and in 2019 she was named one of the Biomedical Engineering Society’s Young Innovators in Cellular and Molecular Bioengineering.

AFFILIATED FACULTY Alpesh N. Amin, M.D. Thomas & Mary Cesario Chair and Professor of Medicine; Biomedical Engineering; Paul Merage School of Business; Program in Nursing Science Email: anamin@uci.edu

Pierre F. Baldi, Ph.D. UCI Chancellor’s Professor of Computer Science; Biological Chemistry; Biomedical Engineering; Developmental and Cell Biology Email: pfbaldi@ics.uci.edu

Bruce Blumberg, Ph.D. Professor of Developmental and Cell Biology; Biomedical Engineering; Environmental Health Sciences; Pharmaceutical Sciences Email: blumberg@uci.edu

Andrew Browne, M.D. Assistant Clinical Professor of Ophthalmology; Biomedical Engineering Email: abrowne1@uci.edu

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Peter J. Burke, Ph.D. Professor of Electrical Engineering and Computer Science; Biomedical Engineering; Materials Science and Engineering Email: pburke@uci.edu

Hung Cao, Ph.D. Assistant Professor of Electrical Engineering and Computer Science; Biomedical Engineering Email: hungcao@uci.edu

Dan M. Cooper, M.D. Professor of Pediatrics; Biomedical Engineering Email: dcooper@uci.edu

Robert Corn, Ph.D. Professor of Chemistry; Biomedical Engineering Email: rcorn@uci.edu

Nancy A. Da Silva, Ph.D. Professor of Chemical and Biomolecular Engineering; Biomedical Engineering Email: ndasilva@uci.edu

Hamid Djalilian, M.D. Professor of Otolaryngology; Biomedical Engineering Email: hdjalili@uci.edu

James Earthman, Ph.D. Professor of Materials Science and Engineering; Biomedical Engineering Email: earthman@uci.edu

Rahim Esfandyarpour, Ph.D. Assistant Professor of Electrical Engineering and Computer Science; Biomedical Engineering Email: rahims@uci.edu

Gregory R. Evans, M.D. Professor of Surgery; Biomedical Engineering Email: gevans@uci.edu

Lisa Flanagan-Monuki, Ph.D. Associate Professor of Neurology; Biomedical Engineering Email: lflanaga@uci.edu

Ron Frostig, Ph.D. Professor of Neurobiology and Behavior; Biomedical Engineering Email: rfrostig@uci.edu

Zhibin Guan, Ph.D. Professor of Chemistry; Biomedical Engineering Email: zguan@uci.edu

Gultekin Gulsen, Ph.D. Associate Professor of Radiological Sciences; Biomedical Engineering; Electrical Engineering and Computer Science; Physics and Astronomy Email: ggulsen@uci.edu

Ranjan Gupta, M.D. Professor of Orthopaedic Surgery; Anatomy and Neurobiology; Biomedical Engineering Email: ranjang@uci.edu

Frank P. Hsu, M.D. Department Chair and Professor of Neurosurgey; Biomedical Engineering; Otolaryngology Email: fpkhsu@uci.edu

Lan Huang, Ph.D. Professor of Physiology & Biophysics; Biomedical Engineering Email: lanhuang@uci.edu

Christopher Hughes, Ph.D. Director of Edwards Lifesciences Cardiovascular Technology Center and Professor of Molecular Biology and Biochemistry; Biomedical Engineering Email: cchughes@uci.edu

James V. Jester, Ph.D. Professor in Residence, Ophthalmology; Biomedical Engineering Email: jjester@uci.edu

Joyce H. Keyak, Ph.D. Professor in Residence of Radiological Sciences; Biomedical Engineering; Mechanical and Aerospace Engineering Email: jhkeyak@uci.edu

Baruch D. Kuppermann, M.D. Professor of Ophthalmology; Biomedical Engineering Email: bdkupper@uci.edu

Young Jik Kwon, Ph.D. Professor of Pharmaceutical Sciences; Biomedical Engineering; Chemical and Biomolecular Engineering; Molecular Biology and Biochemistry Email: kwonyj@uci.edu

Jonathan Lakey, Ph.D. Professor of Surgery; Biomedical Engineering Email: jlakey@uci.edu

Arthur D. Lander, Ph.D. Donald Bren Professor of Developmental and Cell Biology; Biomedical Engineering; Logic and Philosophy of Science; Pharmacology Email: adlander@uci.edu

Guann-Pyng Li, Ph.D. Director of the UCI Division of the California Institute for Telecommunications and Information Technology; Director of the Integrated Nanosystems Research Facility and Professor of Electrical Engineering and Computer Science; Biomedical Engineering; Chemical and Biomolecular Engineering Email: gpli@uci.edu

Jack Lin, M.D. Professor of Clinical Neurology; Biomedical Engineering Email: linjj@uci.edu

John Lowengrub, Ph.D. UCI Chancellor’s Professor of Mathematics; Biomedical Engineering; Chemical and Biomolecular Engineering Email: jlowengr@uci.edu

Ray Luo, Ph.D. Professor of Molecular Biology and Biochemistry; Biomedical Engineering Email: rluo@uci.edu

Marc J. Madou, Ph.D. UCI Chancellor’s Professor of Mechanical and Aerospace Engineering; Biomedical Engineering; Chemical and Biomolecular Engineering Email: mmadou@uci.edu

UCI Department of Biomedical Engineering

John Middlebrooks, Ph.D.

Professor of Otolaryngology; Biomedical Engineering; Cognitive Sciences; Neurobiology and Behavior Email: j.midd@uci.edu

Sabee Molloi, Ph.D. Professor of Radiological Sciences; Biomedical Engineering Email: symolloi@uci.edu

Jogeshwar Mukherjee, Ph.D. Professor and Director, Preclinical Imaging; Radiological Sciences, School of Medicine; Biomedical Engineering Email: j.mukherjee@uci.edu

J. Stuart Nelson, M.D., Ph.D. Professor of Surgery; Biomedical Engineering Email: jsnelson@uci.edu

Qing Nie, Ph.D. Professor of Mathematics; Biomedical Engineering Email: qnie@math.uci.edu

Pranav Patel, M.D. Chief, Division of Cardiology; Director of Cardiac Catheterization Laboratory and Cardiac Care Unit (CCU) and Health Sciences Associate Clinical Professor of Medicine; Biomedical Engineering Email: pranavp@uci.edu

Medha Pathak, Ph.D. Assistant Professor of Physiology and Biophysics; Biomedical Engineering Email: medhap@uci.edu

Eric Potma, Ph.D. Professor of Chemistry; Biomedical Engineering Email: epotma@uci.edu

David J. Reinkensmeyer, Ph.D. Professor of Anatomy and Neurobiology; Biomedical Engineering; Mechanical and Aerospace Engineering; Physical Medicine and Rehabilitation Email: dreinken@uci.edu

Phillip C-Y Sheu, Ph.D. Professor of Electrical Engineering and Computer Science; Biomedical Engineering; Computer Science Email: psheu@uci.edu

Andrei M. Shkel, Ph.D. Professor of Mechanical and Aerospace Engineering; Biomedical Engineering; Electrical Engineering and Computer Science Email: ashkel@uci.edu

Zuzanna S. Siwy, Ph.D. Professor of Physics and Astronomy; Biomedical Engineering; Chemistry Email: zsiwy@uci.edu

Ramesh Srinivasan, Ph.D. Professor of Cognitive Sciences; Biomedical Engineering Email: r.srinivasan@uci.edu

Peter Tseng, Ph.D. Assistant Professor of Electrical Engineering and Computer Science; Biomedical Engineering Email: tsengpc@uci.edu Vasan Venugopalan, Sc.D. Department Chair and Professor of Chemical and Biomolecular Engineering; Biomedical Engineering; Mechanical and Aerospace Engineering; Materials Science and Engineering Email: vvenugop@uci.edu

Szu-Wen Wang, Ph.D. Professor of Chemical and Biomolecular Engineering; Biomedical Engineering Email: wangsw@uci.edu

H. Kumar Wickramasinghe, Ph.D. Henry Samueli Endowed Chair in Engineering; Professor of Electrical Engineering and Computer Science; Biomedical Engineering; Chemical and BiomolecularEngineering Email: hkwick@uci.edu

Brian Wong, M.D. Professor of Otolaryngology; Biomedical Engineering Email: bjwong@uci.edu

Xiangmin Xu, Ph.D. Professor of Anatomy and Neurobiology; Biomedical Engineering; Electrical Engineering and Computer Science; Microbiology and Molecular Genetics Email: xiangmin.xu@uci.edu

Albert Fan Yee, Ph.D. Professor of Chemical and Biomolecular Engineering; Biomedical Engineering Email: afyee@uci.edu

Fan-Gang Zeng, Ph.D. Director of Hearing Research and Professor of Otolaryngology; Anatomy and Neurobiology; Biomedical Engineering; Cognitive Sciences Email: fzeng@uci.edu

Weian Zhao, Ph.D. Associate Professor of Pharmaceutical Sciences; Biomedical Engineering Email: weianz@uci.edu

BME Discovery

EXECUTIVE ADVISORY BOARD Zoran Nenadic UC Irvine Bill Link Versant Ventures David Cuccia Modulated Imaging Bruce Feuchter Stradling Yocca Carlson & Rauth Stanton Rowe NXT Biomedical Thomas Yuen PrimeGen Biotech Nicholas Alexopolous Broadcom Foundation Vasudev Bailey Quid Thomas Frinzi Johnson & Johnson Vision Thomas Burns Glaukos Corp.

David Bardin Glaukos Corp.

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UCI Department of Biomedical Engineering

The educational mission of the biomedical engineering program at UC Irvine is to provide students with rigorous, multidisciplinary training that enables graduates to be leaders and innovators in bioengineering and biomedical professions.

This is accomplished by developing and offering curricula that integrate engineering sciences, life sciences, clinical medicine, research and engineering design in collaboration with local biomedical device and biotechnology companies.

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BME Discovery

NONPROFIT ORG. U.S. POSTAGE

PAID

Department of Biomedical Engineering

Santa Ana, CA Permit No. 1106

University of California, Irvine Samueli School of Engineering Department of Biomedical Engineering 3120 Natural Sciences II Irvine, CA 92697-2715

Invest in a brilliant future.

BE A BME SUPPORTER. We believe in meeting tomorrow’s technological challenges by providing the highest-quality engineering education and research rigor today.

We invite you to invest in the future of UC Irvine’s biomedical engineering program. It is through private donations like yours that we can continue to provide outstanding opportunities for our students and researchers. Your contribution, regardless of amount, makes a difference toward what BME can accomplish.

To find out more about supporting the advancement of the biomedical engineering department, please visit https://ua-web.uadv.uci.edu/egiving.

From the “area of support” drop-down menu, select Engineering School and from the “gift designation” drop-down menu, you may either select Biomedical Engineering or Biomedical Graduate Fellowship Fund.

This will ensure that your support will go directly to the department. For more information, please contact Angelique Andrulaitis, senior director of development, aandrula@uci.edu or (949) 824-3977.

To learn more about the BME department, please visit http://engineering.uci.edu/dept/bme