UCI Biomedical Engineering Discovery Magazine Fall 2021

BME DISCOVERY DEPARTMENT OF BIOMEDICAL ENGINEERING

FALL 2021

Inspiring Engineering Minds to Advance Human Health

FROM THE CHAIR

This summer in California feels a lot like last year’s— an anxiety-filled rollercoaster of wildfires and a pandemic whose outlook seemed very promising mere weeks ago. Perhaps it’s a befitting conclusion of the most challenging academic year that most of us have ever experienced. Despite these unusual and trying circumstances, we have had a remarkable year, with exciting developments in all aspects of our academic enterprise.

Our faculty continue to receive recognition for their research excellence and impact. I am very proud of our senior colleagues, who were honored for their lifetime achievements.

Kyriacos (Kerry) Athanasiou was elected to the National Academy of Medicine, joining a small group of engineers to hold this coveted distinction. Michael Berns became a Fellow of the United Kingdom’s Royal Society of Medicine, and Enrico

Gratton received the Britton Chance Biomedical Optics Award. Our mid-career faculty are following in stride by receiving recognitions from professional societies and foundations. Our graduate student and postdoctoral trainees continue to shine by winning highly competitive fellowships from federal agencies, foundations and the private sector.

Along with the accolades, groundbreaking work is happening within our collaborative research ecosystem. Our researchers continue to thrive and produce discoveries that are pushing the boundaries of knowledge. In this magazine, you will find remarkable stories such as how to give cells the ability to write their experiences into their genomes. You will also learn about a new imaging method that shows promise in detecting migrating cancerous cells.

A thought-provoking perspective highlights gender bias in the treatment of common joint ailments. To keep our research thriving, our faculty have set another record in terms of extramural funding. These are just a few of the many exciting developments supporting our research, teaching and mentoring mission.

This magazine is about the people I am proud to call colleagues. I invite you to pay us a virtual visit (https://engineering.uci.edu/dept/ bme) to get to know us better. Once it becomes safe to travel again, we look forward to hosting you in person on the beautiful UCI campus.

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

PAGE 4 Biomedical engineers develop new spectral fluorescence lifetime imaging method for investigating live cells.

PAGE 28 Researchers spotlight disparities in knee and jaw joint treatments.

C NTENTS

PAGE 16 A new DNA recorder CHYRON works like a barcode or biography for cells.

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By the Numbers

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Imaging Crusaders

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Research & Funding

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Recording Cells’ Stories

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Faculty Accolades

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Helping Humans Heal

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Treatment Disparities

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Student Merits

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BME 3 Online

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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: Amy Ruth Editor-in-Chief: Shelly Nazarenus Art Direction: Michael Marcheschi, m2dg.com Publisher: Mike Delaney, Yebo Group

BY THE NUMBERS UC IRVINE DEPARTMENT OF BIOMEDICAL ENGINEERING The department, founded in 2002, merges UCI’s strengths in medicine, biological sciences and engineering. The BME faculty are continuously recognized for their excellence and groundbreaking research activities. 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.

Biomedical Computational Technologies

STUDENT POPULATION

Biomedical Nanoscale Systems

128

Biomolecular/Genetic Engineering

GRADUATE STUDENTS (FALL 2020)

Biophotonics Cardiovascular

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Neuroengineering

556

UNDERGRADUATE STUDENTS (FALL 2020)

Tissue Engineering

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RESEARCH & EXPENDITURES

RESEARCH THRUSTS

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

$37 .3 MILLION RESEARCH EXPENDITURES (2019-20)

UCI Department of Biomedical Engineering

FACULTY & RECOGNITION

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63

FACULTY MEMBERS

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NATIONAL ACADEMY OF MEDICINE MEMBER

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ROYAL SOCIETY OF MEDICINE FELLOW

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NIH NEW INNOVATOR AWARDS

DISTINGUISHED PROFESSORS

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NATIONAL ACADEMY OF INVENTORS

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NSF CAREER AWARDS

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AFFILIATED FACULTY

DARPA YOUNG FACULTY AWARD

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ENDOWED CHAIR AND PROFESSORSHIPS

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IMAGING CRUSADERS

Researchers develop new technique to capture metastasizing cancer cells LORI BRANDT

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W

HILE THE FICTIONAL SUPERMAN FAMOUSLY USED HIS “X-RAY VISION” TO PENETRATE BUILDINGS AND CAPTURE CRIMINALS, UCI’S BIOMEDICAL ENGINEERS ARE DEVELOPING A REAL-LIFE ADVANCED IMAGING TECHNIQUE TO CATCH ANOTHER TYPE OF OFFENDER, THE MIGRATING CANCER CELL. Being able to precisely characterize living cells, such as malignant cancer cells, will help researchers better understand how cellular processes are related to disease progression as well as determine treatment effectiveness.

Led by Enrico Gratton, Distinguished Professor of biomedical engineering and director of the Laboratory for Fluorescence Dynamics, the Samueli School team has created a new fast, robust microscopy imaging technique that could better capture detailed and precise information of cellular processes. The technique combines two broadly applied microscopy methods – spectral imaging and fluorescence lifetime imaging microscopy (FLIM) – by creating a true parallel detection system for simultaneous measurements that can be processed in real time. Their research is published in Nature Methods.

UCI Department of Biomedical Engineering

The new Phasor S-FLIM imaging method allows researchers to obtain precise and detailed information from a living cell.

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“Th is new technique works on live cells; there is no need for fi xation,” says Gratton. “We believe the information we obtain could be augmented by genomic and proteomics data. More importantly, Phasor S-FLIM can provide results in tissues that are difficult to measure using these omics approaches. Th is would be a new paradigm for researchers who are using advanced imaging to solve hard-to-investigate living cells and gain important insights on human health.”

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The new fluorescence microscopy method uses the color properties and emission duration of fluorescent dyes to achieve high specificity and sensitivity in imaging living cells. It is an extremely valuable tool in biomedical research as most of today’s microscopes rarely obtain emission spectrum and fluorescence lifetime, and only a handful can do it on the same microscope. Th is process is, however, very slow and requires high power for illumination, greatly limiting the acquisition speed and damaging the sample.

Moreover, many processes in the cellular machinery happen at the same time and can’t be addressed with current technologies. For example, the researchers built a 3D model (spheroid) of a breast cancer tumor in the lab and observed that some cells, after a while, leave the spheroids and migrate. Later, these traveling cells form metastases and secondary tumors, so they are ideal targets for further investigation and research on antitumor treatments.

With the Phasor S-FLIM system, super tiny glow-in-the dark chemical compounds called fluorophores are used to “color” a specific element of the cells. Fluorophores are just a few nanometers in size and become dark in a few nanoseconds, making their detection challenging. With a typical microscope, researchers can take only black-and-white pictures of cells, limiting the amount of information that can be collected.

Th is new technology can not only accurately distinguish the colors (spectral information) but also simultaneously identify cells by how fast they return to dark once the light fades (lifetime information).

Previously, this combination of methods was inefficient and slow in capturing and processing the information. Being capable of distinguishing many glowing cells at the same time can speed up the analysis of biological samples.

“With Phasor S-FLIM, we obtain the spectral and lifetime information simultaneously by dividing the light emitted by the fluorophores according to color using a diff raction grating, which is similar to a prism, and collecting the light with an array of 32 detectors. Each detector collects a specific color and is coupled with state-of-the-art electronics capable of obtaining the lifetime information within nanoseconds,” says Lorenzo Scipioni,

postdoctoral scholar in biomedical engineering and fi rst author of the research.

“The amount of information gathered is large and challenging to process in real time. For instance, for every single image acquired in just a few seconds, we obtain almost 8,200 images! To overcome this limitation, we applied our phasor approach, which is an advanced computational method that performs much faster than conventional methods and can allow for the whole dataset to be processed in under a second.”

The team tested the new method on four common problems in fluorescence microscopy imaging.

Blind unmixing: Having access to such a wealth of information allowed the researchers to develop an unmixing algorithm capable of separating both the spectral and lifetime information from the sample without knowing anything about the sample’s composition.

UCI Department of Biomedical Engineering

Th is has important applications in tissue imaging, in which many components of the tissue (metabolites, collagen, melanin and vitamins) intrinsically emit fluorescence with color and lifetime information that is difficult to unmix with other imaging methods.

Forster Resonance Energy Transfer (FRET): FRET is a powerful technique capable of obtaining a quantitative measure of molecular interaction at distances below 10 nanometers. Unfortunately, its use in cells is limited by a poor understanding of the system’s photophysics and its relatively low brightness. With Phasor S-FLIM, scientists can apply FRET with a precision several times higher than current methods, allowing them to use it on challenging samples such as for the analysis of biosensors, engineered proteins capable of sensing physiological changes inside living cells.

Environment-sensitive dyes: These are a class of fluorophores that change color and/ or lifetime in response to changes in the sub-cellular environment at the nanoscale.

With Phasor S-FLIM, researchers can characterize both changes at the same time, capturing more robust results and allowing them to combine multiple dyes together and

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obtain information about the structural and chemical composition of DNA, lipids and organelles inside living cells.

Physiological fingerprinting: By using a combination of dyes and Phasor S-FLIM, the researchers were able to simultaneously obtain information about lipid content, membrane fluidity and metabolism that can be used to highlight which cells will form metastases in model tumor spheroids and provide insights on novel therapies for targeting them.

Other collaborators on the research include Alessandro Rossetta, FLIM Labs founder, and Giulia Tedeschi, UCI biomedical engineering research junior specialist.

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RESEARCH & FUNDING

LIU RECEIVES NIH TRANSFORMATIONAL RESEARCH AWARD Biomedical engineer Chang Liu is developing a system for making antibody generation a routine and widely accessible process. He won a Director’s Transformative Research Award from the National Institutes of Health under its High-Risk, High-Reward Research Program for the work and will receive $8.4 million over five years.

Liu is one of only nine to receive this recognition.

“It is hard to overstate the importance of monoclonal antibodies in the life sciences,” said Liu, associate professor of biomedical engineering. “Antibodies are critical tools in biomedical research and diagnostics, and they are a growing class of therapeutics to combat cancer and pathogens up to and including the virus responsible for COVID-19.”

Liu said current methods for making custom antibodies are slow, costly, inaccessible to most researchers and often unsuccessful. His NIH proposal centers on simplifying the process through continuous and rapid evolution of high-quality antibodies requiring only the simple culturing of yeast cells.

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He said his autonomously evolving yeast-displayed antibodies technology could have a transformative impact across the biomedical field by turning monoclonal antibody generation into a rapid, scalable and accessible process where any lab with standard molecular biology capabilities can generate custom antibodies on demand.

“We believe this can be achieved by combining our new technology for continuous protein evolution, a yeast antigenpresenting cell that we will engineer, and cutting-edge generative machine-learning algorithms for antibody library design,” he said.

Liu said that in addition to the continuous directed-evolution techniques that he has invented in his UCI laboratory, the project will rely on antibody design and artificial intelligence expertise provided by his collaborators on the project, Andrew Kruse and Debora Marks at Harvard Medical School.

The project could potentially result in “an explosion of crowdsourced antibody sequence data that will train our machinelearning algorithms to design better antibody libraries for our autonomous evolution system, starting a virtuous cycle,” he said.

In addition to contributing to cancer and anti-viral therapies, Liu said he and his fellow researchers will attempt to generate nanobodies against biogenic receptors that respond to acetylcholine, adrenaline, dopamine and other neurotransmitters. The goal of this work will be to develop a better understanding of psychopharmaceuticals in neurobiology and addiction.

“In the past, the Transformative Research Award has allowed some of the most ambitious and impactful ideas in biomedicine to blossom, and several previous winners are scientific heroes of mine,” said Liu. “We have big shoes to fill, but we are up to the challenge.”

UCI Department of Biomedical Engineering

RESEARCHERS ADVANCE EFFORTS TO CHARACTERIZE MUCOSAL HEALTH Approximately 50 million Americans suffer from painful sinus and allergic nasal upper respiratory ailments. Known medically as chronic rhinosinusitis and allergic rhinitis, the resulting headaches, stuffy/runny noses, itchy eyes and sneezing are responsible for more than $35 billion a year in healthcare costs and 3.5 million missed workdays.

UCI biomedical researchers are building a technology that could help doctors treat these ailments. With a $2.3 million, four-year R01 award from the NIH’s National Institute of Biomedical Imaging and Bioengineering, Zhongping Chen and Dr. Brian Wong are creating an innovative in vivo imaging system called phase-resolved spectrally encoded endoscope (PR-SEE).

“Right now, the response to therapy is entirely based on patientreported outcomes,” said Wong, an otolaryngologist/facial surgeon who has a joint appointment in biomedical engineering.

The PR-SEE will employ two distinct imaging techniques to overcome current limitations on in vivo cilia imaging. (Cilia are tiny, hairlike structures on airway cell surfaces that sweep in a rhythmic pattern to transport mucus.) Optical coherence tomography (OCT) uses two scanning mirrors to provide information from deep within tissue.

Spectrally encoded interferometry, a method that uses one mirror, provides faster imaging speed, but cannot achieve deep measurements like OCT. Together, the two techniques can give medical professionals quantitative information they have not had access to. “This has never been done in vivo before,” said Chen, professor of biomedical engineering.

The device will measure ciliary beat frequency (CBF) – the speed cilia sweep. Along with other factors, the CBF determines the efficiency of mucus transport, providing a strong indicator of upper airway health.

The device also will assess amplitude and propagation of the mucosal metachronal waves. “CBF is only one of the many factors that dictate the ability of cilia to transport mucus,” explained Chen. “It is also important to study the sweeping pattern (amplitude) and how well each cilium coordinates with each other (metachronal waves). These quantitative factors will provide a more comprehensive understanding of how airway cilia work, and will go a long way toward determining upper airway health.”

Rhinosinusitis currently accounts for more antibiotic prescriptions than any other diagnosis in ambulatory settings, and severe cases result in 600,000-plus sinonasal operations annually.

Chen added: “This imaging modality establishes an objective means to gauge sinus health and the response to treatment, which will aid us in better development of drugs, devices and other therapies.”

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BOTVINICK TO DEVELOP FIRST-OF-ITS-KIND DIABETES MONITOR Elliot Botvinick, professor of biomedical engineering, has been awarded a three-year, $3.5 million grant from The Leona M. and Harry B. Helmsley Charitable Trust to further the development of an innovative continuous-use monitor for those with Type 1 diabetes. The first-of-itskind device will simultaneously measure insulin, glucose, lactate, oxygen and the ketone body beta-hydroxybutyrate with a single probe inserted just beneath the skin.

Called iGLOBE (Insulin + Glucose + Lactate + Oxygen + BetaHydroxybutyratE) LifeStrip, the monitor utilizes light and chemistry to provide sensing capabilities for multiple analytes, which can be critical for controlling blood glucose and detecting possible dangerous events. The device will include continuous insulin monitoring and improve dosing efficacy by providing real-time feedback on the dynamics of insulin-pump therapy as well as real-time estimates of a patient’s sensitivity to the insulin.

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It is also important to monitor blood glucose in those with Type 1 diabetes, known as insulin dependent diabetes. When blood glucose is elevated above normal values, called hyperglycemia, the body produces a chemical called beta-hydroxybutyrate. Elevated beta-hydroxybutyrate is associated with diabetic ketoacidosis, a dangerous condition, which can result in hospitalization or death. iGLOBE monitors this chemical to indicate dangerous levels and ensure automated insulin delivery functions properly.

Monitoring lactate, produced during exercise, is also important, as it can indicate changing metabolic states, which can lead to changes in blood glucose hours after exercise. This will improve glucose prediction and improve insulin dosing.

“Clinical evidence suggests that both beta-hydroxybutyrate and insulin sensing would improve outcomes and decrease the rates of hospitalization, severe morbidity and death associated with hypo- and hyperglycemia,” said Botvinick, who is also associate director of UCI’s Edwards Lifesciences Center for Advanced Cardiovascular Technology and professor of surgery at UCI Beckman Laser Institute (BLI).

The addition of beta-hydroxybutyrate and insulin monitoring capabilities has the potential to be life-altering. “When taken together, glucose, lactate, beta-hydroxybutyrate and insulin monitoring can transform the care of people with Type 1 diabetes,” Botvinick said. “iGLOBE can improve glucose control, compensate for glucose variations associated with exercise, inform of possible or current diabetic ketoacidosis and inform of failing or failed insulin delivery.”

Botvinick is collaborating with Gregory Weiss, UCI professor of chemistry, molecular biology and biochemistry; and David O’Neal, M.D., professor of endocrinology at Australia’s University of Melbourne.

The team includes John Weidling, BLI associate project scientist, and biomedical engineering graduate students Toni Wilkinson and Dat Nguyen.

UCI Department of Biomedical Engineering

TEAM FOCUSED ON BIOLOGIC IMPLANT FOR SPINAL FACET JOINTS Kyriacos Athanasiou, Henry Samueli Chair in Engineering and Distinguished Professor of biomedical engineering, is creating a biologic implant for the spinal facet joint. With a $2 million NIH grant, the Samueli School research team, led by Athanasiou, will be the first to focus on the treatment of facet joint degeneration, a highly prevalent contributor to back pain.

“The goal of the project is to use selfassembled cartilage, which is a technique for cartilage tissue engineering that my group has been developing for over a decade, to generate an implant that can restore structure and function to degenerated facet joints,” Athanasiou said.

Current treatment options for the condition are limited. “It has been found that degeneration in the facet joints is present in 70 percent of the population by the age of 30,” said team member Rachel Nordberg, a postdoctoral scholar in biomedical engineering. “As we age, this degeneration continues to progress, afflicting essentially the entire population by the age of 60.”

Co-investigator Jerry Hu, a program manager in the Department of Biomedical Engineering, added: “Unfortunately, management of facet pain is short-lived. On average, treatments such as neurotomy last for only nine months, which is why we’re seeking to develop novel living tissue implants for the facet.”

Other collaborators on the NIH-funded project include Drs. Michael Yaszemski and Benjamin Elder, spine surgeons at the Mayo Clinic.

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COLLABORATIVE EFFORT TO IMPROVE EPILEPSY SURGERY In the United States, 3.4 million people live with active epilepsy, a disorder in which nerve cell activity in the brain is disturbed, causing seizures. The neurological disorder is usually treated with medication. However, for people with severe epilepsy, surgery may be the best option.

Beth Lopour, associate professor of biomedical engineering, is collaborating with pediatric epilepsy specialists at Children’s Hospital of Orange County (CHOC) on research that she hopes will improve the quality of life for children with the most severe cases of epilepsy.

She won a $1.8 million five-year R01 grant from the NIH National Institute of Neurological Disorders and Stroke to develop and validate computerized tools to more accurately and objectively identify regions in the brain where epileptic seizures originate.

Currently, to determine where the seizures are originating, clinicians implant electrodes directly onto a patient’s brain to continuously record electrical activity. This invasive recording may last days to weeks, until enough data is captured to proceed with surgery. Surgeons and epilepsy specialists then use this information, combined with brain imaging and other test results, to guide removal of the seizure-generating brain tissue.

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The problem is current epilepsy surgery does not always work to curtail seizures. The majority of patients remain on anti-seizure medications after surgery, and roughly half of patients continue to have seizures.

“The long-term goal of this grant is to improve the outcomes of patients undergoing epilepsy surgery by developing more accurate methods to localize seizure-generating tissue,” said Lopour.

Specifically, Lopour is developing recording techniques, computational algorithms and data analysis methods to better identify and measure high-frequency oscillations, the short bursts of high-frequency electrical activity that occur in epileptic patients’ brains. Recent research has suggested that HFOs are a good biomarker of where seizures originate, and surgically removing HFO-generating brain tissue increases the likelihood of seizure freedom.

Lopour explains that seizures are unpredictable and scary, which not only affects children but also their caregivers and family. She is grateful for the support and participation from the patients and their families at CHOC. “Participating in clinical research is a brave and selfless act, and we are continuously humbled by the trust and support these families afford us,” said Lopour. “It is only because we have such great partnerships between researchers, clinicians and families that we can pursue such impactful work, and we sincerely hope our endeavors lead to improvements in the care and outcomes of patients with epilepsy.”

Lopour is working with CHOC Drs. Daniel Shrey, pediatric neurologist and epilepsy specialist, and Joffre Olaya, pediatric neurosurgeon.

UCI Department of Biomedical Engineering

NEW SINGLE CELL ANALYSIS TECHNOLOGY HOLDS PROMISE TO ADVANCE DISEASE DIAGNOSIS UCI biomedical engineering researchers have been awarded $1.1 million from the NIH National Cancer Institute’s Innovative Molecular Analysis Technologies program to further their work on an integrated microfluidic platform that could help dramatically change the way tumor tissue is clinically evaluated. With three years of funding support, the team, led

by Jered Haun, associate professor, will be able to test the technology on human tissue samples. The results could help scientists make progress in disease diagnosis and drug development.

Solid tumors are complex mixtures of different cell types, and these differences are key factors driving disease progression, metastasis and drug resistance. “Assessing cellular heterogeneity and identifying key driver cells are critical for understanding tumor biology, and for creating the most powerful clinical diagnostics,” said Haun. “Targeted therapies must be directed toward the most important cell types if effective cures are to be achieved. With this technology applied in clinical settings, we hope to help usher in an era of precision molecular medicine.”

Currently, single cell analysis studies are hindered, as tissues must first be dissociated into single cell suspensions using methods that are often inefficient, labor-intensive and highly variable. Importantly, certain cell types can be released more easily than others, which will bias the single cell analysis assay and lead to incorrect conclusions.

The new platform will combine four separate microfluidic device technologies that Haun has pioneered. The devices were designed to work sequentially, starting from tissue specimen digestion, through dissociation and filtration to finally extracting single cells. Any remaining cell clusters would be recirculated back into the front end of the device to maximize cell recovery. Single cells will be continuously extracted from the system as soon as they are ready, within minutes after dissociation, to prevent overtreatment and maintain viability.

“This multifaceted approach will enable us to tailor flow properties and shear forces to the appropriate magnitude and size scale, resulting in gradual and ultimately complete breakdown of tissue in a fast, efficient and gentle manner,” said Haun.

The researchers will test each device separately using human breast, pancreatic and prostate tumor tissue specimens. They will then integrate all the devices into a versatile system that will operate one, multiple or all devices, as well as establish continuous processing. Finally, they will evaluate suspensions using single-cell RNA sequencing, which assesses each cell’s gene expression profile, to determine whether cell subtypes are biased by any device component and/or released at different time points during the process.

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IMMUNE SYSTEM RESEARCH BENEFITS WOUND HEALING The key to unlocking the mystery of how the immune system helps heal wounds appears to be in understanding the role of a protein called Piezo1, according to research by Wendy Liu. The professor of biomedical engineering published research on Piezo1 in Nature Communications.

Macrophages, a type of white blood cell in the immune system, perform different functions during immune responses to pathogens and injuries. Liu’s research found that macrophages lacking Piezo1, a mechanically activated cation channel protein, showed reduced inflammation and enhanced wound healing.

“In our study, we examined how cells of the immune system – specifically macrophages – respond to the stiffness of a material,” Liu explained. “Stiffness is important in many biological contexts. For example, when medical devices are implanted into the body, the materials they are made out of are usually much stiffer than the tissue around it, and these implants can cause inflammation and scarring that is mediated by macrophages. In addition, tumors or diseased cardiovascular tissues are often stiffer than healthy tissue, and macrophage activity is also involved in these diseases.”

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The study revealed that Piezo1, which allows ions like calcium to pass through cell membranes, is a mechanosensor (able to sense mechanical stimuli) of stiffness in macrophages, and its activity modulates the behavior of these cells. In stiff environments, the ion channel becomes activated, causing more calcium in the cells and higher levels of inflammation.

Macrophages cultured on soft substrates have reduced inflammatory activation when compared to cells adhered to glass or other stiff substrates.

“We found that macrophages that lack the Piezo1 channel could not sense different stiffness environments,” Liu said.

“Furthermore, stiffer implants usually cause more scarring compared to soft implants. However, when Piezo1 was not present, scarring around the stiff implant was much less, and more like the response to a soft implant.

“By identifying a molecule that is required for sensing different stiffness environments, we can start thinking about therapies that target Piezo1 and control inflammation.”

Liu’s research was a collaboration with Medha Pathak and Michael Cahalan, both from the UCI School of Medicine.

COLLABORATIVE GRANT FURTHERS EARLY HEART DEVELOPMENT PROJECT Biomedical engineers from UCI and Oregon Health and Science University are collaborating on research to better understand how blood flow and genetic processes influence early heart development. Their project has been awarded two, three-year collaborative grants from the National Science Foundation Division of Chemical, Bioengineering, Environmental, and Transport Systems totaling $650,000.

Congenital heart defects are present at birth and can affect the structure of a baby’s heart and the way it works. About 1 in every 4 babies born with a heart defect has a critical congenital heart defect and will need surgery or other procedures in the first year of life, according to the Centers for Disease Control and Prevention. Why most defects come about and how they eventually lead to heart failure remains unknown.

UCI’s Dr. Arash Kheradvar, professor of biomedical engineering, will join OHSU’s Sandra Rugonyi, professor of biomedical engineering, to conduct the research. Kheradvar explains that although scientists speculate both blood flow and genes contribute to heart development, it is not yet known how they interact with each other and the synergistic roles they play in heart malformations.

“Using advanced imaging methods and computational simulations, our teams plan to unravel how altered blood flow affects programmed genetic processes, and conversely how altering genetic processes changes blood flow, leading to hearts with defects,” said Kheradvar.

Using two avian models of heart development, the research has three main objectives: to determine blood flow and flow-induced stresses during normal and aberrant cardiac formation through advanced engineering methods; identify and quantify cellular responses to normal and abnormal heart development by generating spatiotemporal maps of cardiac adaptation; and ascertain the genetic and epigenetic adaptations in cardiac tissues using sequencing technologies.

More broadly, research results will provide fundamental knowledge on embryonic heart development, help with strategies to improve diagnosis of heart defects and preventing heart malformations, and eventually guide early fetal interventions to repair cardiac defects and promote healthy heart function.

The award also supports outreach activities involving rising high school students in California and Oregon. UCI’s ASPIRE (Access Summer Program to Inspire, Recruit and Enrich) will be implemented at OHSU. UCI Department of Biomedical Engineering

RESEARCHERS USE MICROFLUIDICS TO ASSIST IN AGRICULTURAL MEASUREMENTS Plant researchers search for ways to adapt crops to be more nutritious, resource-efficient and resilient in a variety of climates. Genomics, and more specifically genotyping, which measures genetic identity, play a growing role in this ongoing endeavor to breed new crop varieties. Agricultural companies often perform hundreds of thousands of these genetic measurements each day.

The Samueli School’s Center for Advanced Design and Manufacturing of Integrated Microfluidics (CADMIM), a National Science Foundation-backed collaboration between university researchers and industry partners, has received a new NSF grant to continue their work on a microfluidic device that can sustainably monitor and improve agricultural crop breeding.

The $250,000 Partnerships for Innovation grant from the NSF Division of Industrial Innovation and Partnerships leverages technology created over the last few years by CADMIM researchers. Biomedical engineering Associate Professor Elliot Hui leads the team creating a device that automates the measurement of genetic markers across many plants simultaneously, using microfluidics. The process uses fewer supplies, runs reactions faster and enables the completion of four times the number of tests in a given time frame compared to current technology, all at a fraction of the cost.

The project, a partnership with agricultural plant seed producer KWS SAAT SE & Co., has already achieved proof-of-concept, and the new funds will advance device development and production. The team will use the new grant to transition to a platform that will be faster to manufacture and more conducive to performing the biochemical reactions. They will also work to scale up the device and create a fully functional prototype.

The Partnerships for Innovation grants are specifically targeted to bridge the gap between academic research and commercialization. Through the NSF I-Corps program, the research team will interview 100 potential customers to identify customer needs. A large component of the grant also focuses on leadership and innovation. Hinesh Patel, a graduate student in Hui’s lab, will receive entrepreneurship training to help the team successfully produce and market the technology.

While the original research was geared to the plant agriculture industry, the technology can extend to other applications, including medical research, healthcare and consumer markets like genealogy.

BIOCHIP INNOVATION COMBINES AI AND NANOPARTICLE PRINTING FOR CANCER CELL ANALYSIS A new lab-on-a-chip can help study tumor heterogeneity to reduce resistance to cancer therapies.

In Advanced Biosystems, UCI researchers describe combining artificial intelligence, microfluidics and nanoparticle inkjet printing in a device that enables examining and differentiating cancers and healthy tissues at the single-cell level.

“Cancer cell and tumor heterogeneity can lead to increased therapeutic resistance and inconsistent outcomes,” said lead author Kushal Joshi, former biomedical engineering graduate student. The team’s biochip addresses this problem through precise characterization of a variety of cancer cells from a sample.

“Single-cell analysis is essential to identify and classify cancer types and study cellular heterogeneity. It’s necessary to understand tumor initiation, progression and metastasis in order to design better cancer treatment drugs,” said co-author Rahim Esfandyarpour, assistant professor of electrical engineering and computer science with a joint appointment in biomedical engineering.

His group combines machine learning techniques with accessible inkjet printing and microfluidics technology to develop low-cost, miniaturized biochips that are simple to prototype and capable of classifying various cell types.

In the apparatus, samples travel through microfluidic channels with carefully placed electrodes that monitor differences in the electrical properties of diseased versus healthy cells in a single pass. The researchers’ innovation was to devise a way to prototype key parts of the biochip in about 20 minutes with an inkjet printer, allowing for easy manufacturing in diverse settings. Most of the materials involved are reusable or inexpensive.

The invention also incorporates machine learning to manage large amounts of data the system produces. This improves the accuracy of analysis and reduces dependency on skilled analysts.

Esfandyarpour said, “Our work has potential applications in single-cell studies, in tumor heterogeneity studies and, perhaps, in point-of-care cancer diagnostics – especially in developing nations where cost, constrained infrastructure and limited access to medical technologies are of the utmost importance.”

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RECORDING CELLS’ STORIES New DNA recorder CHYRON offers nondestructive observation of cells for lineage tracing and recording

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TONYA BECERRA

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ISTORIES HOLD KEYS TO UNDERSTANDING THE PRESENT AND ANTICIPATING THE FUTURE BY LOOKING AT THE PAST. But how do you tell the history of a cell if you can’t watch what it does over time because it is deep within a living animal? What if measuring the properties of a cell requires you to destroy it so that you can never get a complete history?

And how do you track the history of not just one but millions or billions of cells?

A new DNA recorder called CHYRON (Cell History Recording by Ordered Insertion) changes the way researchers can study cell histories by giving cells the ability to write their experiences into their own genomes, as a growing DNA barcode. Later on, researchers can sequence the barcodes to find out what cells experienced, including their relationship to other cells or how much of an important biological signal the cell saw during its life. In essence, CHYRON gives cells the ability to hold on to their pasts so that we can deduce how a cell’s past may have influenced its future. This will help us understand complex biological questions such as how organisms develop or what causes a cancer to spread throughout a patient.

Chang Liu, UCI Samueli School associate professor of biomedical engineering with joint appointments in chemistry as well as molecular biology and biochemistry, and Theresa Loveless, postdoctoral scholar in biomedical engineering, created CHYRON. They detail their findings in the March 22, 2021, issue of Nature Chemical Biology.

UCI Department of Biomedical Engineering

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“The challenge that we specifically tackled in this paper is to advance the way that DNA recorders record information,” says Liu. “Previous systems record information by creating deletions in DNA, whereas CHYRON records information by writing new DNA.” This means that cells can use CHYRON to capture a new experience without destroying or corrupting its recording of a previous experience.

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Liu likens CHYRON to the process of writing a biography. “If you find someone who is interesting and decide to write a biography about them, you’ll ask the person, ‘What happened in your life that made you this way?’ We want to be able to do the same thing with cells. Unfortunately, cells don’t naturally remember what happened to them. And they can’t tell you. But with these technologies, you can force a cell to log what has happened to it, so that when it becomes interesting and you actually choose the cells you want to study, they will be able to reveal their memories.”

Loveless points out that for cells, it is not just one biography that we want to read, but millions or billions, each written by a different cell. “Our goal is to have each cell write its experiences by generating a unique barcode,” Loveless says. “As the cell is growing and experiencing new things, it updates its barcode. The patterns in the barcode can be used to infer cellular histories whereas the exact sequence of a barcode marks each cell uniquely.”

The impact of having the memories of millions and eventually billions of cells is deep and far reaching. These cell memories can reveal insights into how mammals develop and also offer critical information about diseases like cancer.

“This is a tool for research,” Loveless explains. “For example, there’s still a lot we don’t know about multicellular developmental

processes. How do we get from zygote to a mouse?

“For very simple organisms such as the roundworm C. elegans, researchers can physically watch development – there are only approximately 1,000 cells in the adult worm.

But mammalian development involving billions and trillions of cells is just a whole other ballgame. But that ballgame is what’s most relevant to understanding ways in which our development might make us sick.”

Cancer is a good example. The fact that it metastasizes is what makes it deadly. When the disease progresses throughout the body, that is when it is the most devastating to the patient. With CHYRON, the researchers hope to learn more about how metastasis works.

“Take a cell that’s in a primary tumor,” Loveless says. “In order to actually form a new, metastatic tumor in another part of the body, the cell has to move out of the primary tumor, get into the blood or the lymph and travel through there and stay alive, evading potential immune surveillance. Then, it has to crawl out of the circulation into a new location and be able to find a place there, find cells that can help its growth, make sure it’s close enough to a blood vessel to get food and oxygen, and then start growing again and grow a whole other tumor.”

Identifying, targeting and killing those metastatic cells with different phenotypes is at the center of potential cancer therapies.

But basic questions like lineage remain unanswered. CHYRON’s innovation is helping provide answers by enabling researchers to keep records in cells, packed with more information that allows them to scale experiments.

“Once metastatic cells are identified,” Loveless says, “We can go back and say: ‘What made you this way?’ It would be much better to target cells that are later going to form a metastasis before they grow out of

control and suddenly you have a hundred million cells you want to try to kill instead of two.”

“This kind of work is highly interdisciplinary,” Liu says. “We’re developing the technology that applies to all sorts of different fields and requires all sorts of different expertise. And so you need a university like UCI to really bring this to fruition.”

Paper authors also include UCI biomedical engineering doctoral student Courtney K. Carlson, former Liu Lab junior specialists Joseph H. Grotts and Mason W. Schecter, as well as UCI computer science professor Xiaohui Xie and doctoral student (now alumna) Elmira Forouzmand. Three undergraduates also contributed to the research and are authors on the paper: Michelle Ficht, Beide Liu and Guohao Liang, now a first-year biomedical engineering doctoral student.

Commenting on the undergraduates, Loveless enthuses, “They absolutely contributed intellectually. They at various points either helped me with computation or experiments – physically doing experiments – or designing protocols to figure out how to make it work.”

“It’s an engineering process,” says Loveless.

“Basically, we have a hypothesis, synthesize the DNA we want, put it in the cells and sequence the DNA of the cells to see if it was having the desired effect. So, design, build, test.”

Although her background was in cell and molecular biology, Loveless decided she wanted to be an engineer. “I really wanted to build new things using the tools that I knew about,” she says “Essentially, I’m trying to make tools that address biological questions.”

By developing a tool like CHYRON, she is much closer to finding answers to those questions.

UCI Department of Biomedical Engineering

“Our goal is

to have each cell write its experiences by generating

a unique barcode.

As the cell is growing and experiencing new things, it updates its barcode.”

BME Discovery

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FACULTY ACCOLADES

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ATHANASIOU NAMED MEMBER OF THE NATIONAL ACADEMY OF MEDICINE Biomedical engineer KYRIACOS A. ATHANASIOU has been elected to the National Academy of Medicine.

Athanasiou was inducted “for inventing, developing, and translating technologies, such as articular cartilage implants and methods for intraosseous infusion, that impact biomedical fields, including orthopedics, maxillofacial surgery, tissue engineering, diabetes, and emergency care,” according to NAM. “I am honored to have been elected a member of the National Academy of Medicine,” said Athanasiou, Distinguished Professor of biomedical engineering and

Henry Samueli Chair in Engineering at UCI. “The recognition, which would not have been possible without the contributions of my students and colleagues at UCI and other institutions throughout my career, highlights the importance of developing a fundamental understanding of the key engineering principles that govern the human body, inventing new ways to treat acquired and congenital defects, and translating those innovations to help improve the human condition.”

Athanasiou specializes in developing advanced engineered tissues and other technologies to address a wide variety of medical issues. He is well known for

making implants that help cartilage heal and repair itself. His scaffolds provided the first cartilage implant to treat joint defects and have been used as bone and dental fillers. Athanasiou’s approach has been to create cartilage constructs to fill in cracks and defects in joints, allowing smooth, pain-free movement.

He and his team pioneered a revolutionary intraosseous infusion device to deliver drugs and other vital substances directly through bones. The technology is now commonly implemented by emergency response and ambulance teams around the world.

UCI Department of Biomedical Engineering

BERNS RECOGNIZED FOR BIOMEDICAL OPTICS CONTRIBUTIONS MICHAEL BERNS, Distinguished Professor Emeritus of biomedical engineering with a joint appointment in developmental and cell biology, and co-founder and founding director of UCI Beckman Laser Institute & Medical Clinic, has been elected as a Fellow of the Royal Society of Medicine in the United Kingdom.

Berns was invited to join the society based on his extensive biomedical optics

contributions in the fields of biology and medicine.

“I am truly honored to be invited to join the Royal Society, especially because it’s the same society that has honored so many elite luminaries of the past,” said Berns.

The mission of the organization is to advance health, through education and innovation. Fellows and Foreign Members of the Royal Society of Medicine are elected

for life through a peer review process on the basis of excellence in science. The society’s 200-year-old history has seen prominent figures in medicine and science as part of its membership and governance. Famous Fellows include Charles Darwin, Louis Pasteur, Edward Jenner and Sigmund Freud. Elected Fellows of the British Royal Society of Medicine are comparable to members of the National Academy of Medicine in the United States.

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BME Discovery

DIGMAN NAMED AN ALLEN DISTINGUISHED INVESTIGATOR Researchers MICHELLE DIGMAN and Jennifer Prescher have won an Allen Distinguished Investigator Award for their project to develop an advanced imaging technique to simultaneously track and manipulate multiple kinds of cells and molecules. Digman, associate professor of biomedical engineering, and Prescher, professor of chemistry, will receive $1.5 million over three years to support their research.

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The two are among 10 new Allen Distinguished Investigators who are working in teams to explore new avenues of basic biology, health, disease and technology development. Theirs is one of four projects, all focused on unanswered questions about how the immune system and metabolism work together in the emerging field of immunometabolism.

“To help scientists better understand the immune system and how it dovetails with metabolism, we need improved toolkits to track and globally probe immune cells and their metabolic functions at once, over time, in a living animal,” said Digman. “We are grateful to have the support of the Allen Institute for this important project.”

She and Prescher are developing a new technique to shine “biological flashlights” on many different immuneand metabolism-related molecules. The bioluminescent phasor technique will ultimately yield a large toolkit of optical tags that can simultaneously light up multiple processes or proteins in a laboratory mouse’s immune system. Once complete, the toolkit would be available for use by any research lab, opening new discoveries about the immune system and its relationship to diet.

UCI Department of Biomedical Engineering

GRATTON RECEIVES AWARD FOR PIONEERING WORK The International Society for Optics and Photonics (SPIE) recognized ENRICO GRATTON with the 2021 Britton Chance Biomedical Optics Award at the SPIE Photonics West virtual conference.

The award cited Gratton’s significant contributions to biophotonics – the science of producing and utilizing photons or light to image, identify and engineer biological materials. SPIE specifically noted his development of innovative ultrafast optical imaging and spectroscopy methods and their integration into microfluidic platforms.

This award was “a great honor” for Gratton who considers Chance, for whom the award was named, a “great friend.” In his conference presentation, Gratton shared his experiences meeting Chance, a National Academy of Sciences member and Olympic gold medalist in sailing who died in 2010, and doing research together.

Gratton is a professor of biomedical engineering and principal investigator for UCI’s Laboratory for Fluorescence Dynamics. A pioneer in the field of biomedical optics, Gratton’s achievements include development of the following technologies: multifrequency phase fluorometry, pulsed-source methods for frequency-domain fluorescence spectroscopy, generalized polarization to study cell membranes, spectral fluorescence lifetime measurements for cell physiology, photo-density waves, quantitative tissue oximetry with near-infrared spectroscopy and optical brain imaging.

During his more than 40-year career, Gratton has disseminated his work to researchers worldwide, trained younger scientists and interfaced successfully with industry. Under his guidance, more than 50 students have earned doctorates, with most currently occupying critical roles in academia and research institutions.

BME Discovery

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KHERADVAR SELECTED FOR ELITE DISTINCTION The American Institute for Medical and Biological Engineering (AIMBE) selected DR. ARASH KHERADVAR for its 2021 Class of the College of Fellows. A professor of biomedical engineering, Kheradvar is recognized for his “contributions to the biomechanics of the cardiovascular system, cardiac imaging, clinical translation of novel heart valve technologies and for his advocacy for racial diversity.”

Election to the AIMBE 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.

As an engineer, physician and scientist, Kheradvar focuses his research on cardiovascular science and engineering with an emphasis on novel cardiac imaging technologies, heart valve engineering and cardiovascular mechanics.

“I am honored to be elected by this elite group of biomedical engineers and scientists as a fellow and to help advance AIMBE’s mission of providing leadership and advocacy in medical and biological engineering for the benefit of society,” he said.

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Kheradvar is one of 174 who were inducted into the AIMBE Fellow Class of 2021 at the virtual Annual Meeting. He is the 12th UCI biomedical engineering faculty member to be named an AIMBE Fellow since the nonprofit organization was established in 1991.

CHESLER RECOGNIZED FOR IMPACT IN MENTORING AND FIGHTING RACIAL INEQUALITY NAOMI CHESLER, professor of biomedical engineering and director of UCI’s Edwards Lifesciences Center for Advanced Cardiovascular Technology, received a Professional Impact Award from the American Institute for Medical and Biological Engineering (AIMBE) at its virtual annual event in March 2021.

Chesler received the mentoring award and was acknowledged for “national leadership in mentoring of women faculty in engineering.” Since arriving at UCI in July 2020, she has initiated a peer faculty mentoring group for women faculty in biomedical engineering. In addition to her cardiovascular and engineering education research, she is well known in the biomedical engineering community as an activist for diversity, equity, inclusion and justice.

“I’m honored to be recognized for my work to promote the careers of women faculty in biomedical engineering,” said Chesler. “We know that diversity drives innovation. Recruiting and retaining women faculty of all races and ethnicities in our discipline is critical to finding solutions to the health and healthcare challenges facing our country.”

Chesler also joined a national network of women deans, chairs and distinguished faculty in biomedical engineering calling upon the National Institutes of Health and other funding agencies to address disparities in allocating support to Black researchers. The group made the call to action in the Jan. 26, 2021, issue of the journal Cell.

In examining the racial inequities and injustices that prevent Black faculty from equitably contributing to science and achieving their full potential, insufficient federal funding for research by Black scientists rose to the top as a key issue.

UCI Department of Biomedical Engineering

KHINE CHOSEN FOR UCI LEADERSHIP POSITION The UCI Division of Undergraduate Education has appointed MICHELLE KHINE, professor of biomedical engineering, as associate dean.

Khine joined the Samueli School of Engineering in 2009 and serves as the director of Faculty Innovation and founding director of the BioENGINE (BioENGineering Innovation and Entrepreneurship) program. She also has joint appointments in chemical & biomolecular engineering, materials science & engineering, and electrical engineering.

The Khine Lab’s mission is dedicated to “improving human health by developing innovative, low-cost and scalable point-ofcare and continuous monitoring solutions.”

Khine inspires and encourages students to pursue laboratory and academic research and entrepreneurship. She is involved with numerous DUE programs, including the ANTrepreneur Center and the Undergraduate Research Opportunities Program. Khine has been committed to campuswide issues of equity, diversity and inclusion for STEM majors, including creating the FITE (Females Impacting Technology Everywhere) Club.

Khine said, “I’m honored and thrilled to serve as associate dean for Division of Undergraduate Education because our undergraduates here at UCI are truly phenomenal.”

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HELPING HUMANS HEAL

Work on a cell regenerative therapy has potential applications in chronic wounds, burns and aging IAN MICHAEL ANZLOWAR

NICK ROMANENKO

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UCI Department of Biomedical Engineering

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N A LAB ON THE UPPER FLOORS OF ENGINEERING HALL, SOMETHING IS GROWING. It’s not a plant. And it’s not an animal.

What Ronke Olabisi is growing in her lab is us. From new skin and retinal tissue to hearts and livers, she’s developing the tools to rebuild and repair the human body.

A UCI assistant professor of biomedical engineering, Olabisi has been working with regenerative tissue for the better part of seven years, using a hydrogel based on polyethylene glycol diacrylate.

“Think about this: When you’re building a building, they put up scaffolding, and people will slowly build that building around the scaffolding,” she says. “Tissue engineers use hydrogels as scaffolding that’s eventually going to be dissolved away in some manner or another. And the hope is that cells can build new tissue around that scaffolding.”

There are a lot of different scaffoldings that researchers use. Some are natural, and some are completely synthetic. Olabisi’s research focuses on an artificial scaffolding, as it gives her the freedom to manipulate the compound molecule by molecule.

“I can observe what happens when I add a particular growth factor and see how the tissue develops,” Olabisi says. “And that kind of manipulation tells me what my scaffolding is doing for my system.”

The scaffolding, which begins as substrate typically purchased from a third party as a powder or liquid, is combined with a special material unique to Olabisi’s work to form the active component in the next step of her research, decellularization. This is the process of isolating the extracellular matrix that makes up the organ requiring repair, which can then be used as a framework on which to rebuild tissue.

Olabisi’s work is not limited to terrestrial applications, however. In 2013, she joined the 100 Year Starship coalition of scientists, researchers and others across the country focused on developing the technologies necessary for humans to travel to and colonize another star system within 100 years.

“In 1961, President Kennedy said, ‘Let’s go to the moon,’ and in 1969, we landed on the moon,” Olabisi explains. “The technology that came out of that completely transformed the world. Now what if they had decided to go in 1869? How would the world have changed with that?”

Research into everything from suspended animation to renewable energy is based on cutting-edge science, and Olabisi’s work is no different. Innovations in her lab may one day have the ability to regenerate decaying tissues. By grafting a synthetic scaffold in an affected area, new treatments could be applied to chronic wounds, could ameliorate the effects of aging and could help soothe burn victims.

While groundbreaking, Olabisi’s work has yet to reach clinical trials.

Traditionally, it can take up to 20 years for an idea to go from conceptualization to market. First comes testing with small animals, typically rodents, then larger mammals and, ultimately, a target population of humans.

“So all of this can take years upon years upon years,” Olabisi says. “However, you can accelerate the speed at which this happens if any component of your work has been tested in people before.”

Fortunately, her main component, polyethylene glycol diacrylate, has undergone extensive human testing, and her cell regenerative therapy is in the preclinical stage, demonstrating that it can help heal wounds faster than traditional methods.

“It’s close to helping people,” Olabisi says, “probably in 10 to 15 years.”

BME Discovery

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TREATMENT DISPARITIES

BRIAN BELL

Study suggests improved remedies for a problem affecting millions of Americans

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In a study in the journal Cell Reports Medicine, UCI researchers discussed the similarities and differences between treatments for disorders of the knee and TMJ, suggesting ways to improve outcomes for people suffering from jaw pain.

UCI Department of Biomedical Engineering

I

F YOU HAVEN’T HAD KNEE SURGERY, YOU MAY HAVE A FRIEND OR RELATIVE WHO HAS.

But do you know anyone who has had an operation on their jaw?

Although the temporomandibular joint is crucial to speaking, chewing and even breathing, treatments for TMJ disorders are far less common than those for the knee.

Why that’s the case – and what can be done to improve how modern medicine handles problems with these two vital body parts – was recently examined by biomedical engineering researchers at the UCI and other institutions. The results of the team’s comparative analysis were just published in the journal Cell Reports Medicine.

The key message of the study is that while the knee and TMJ are both heavily used joints that are subject to cartilage afflictions, the knee orthopedics field enjoys considerably higher funding for research, a wider array of engineered tissues and joint replacement options, and overall higher quality treatments.

“A thoroughgoing research, funding and treatment ecosystem exists for the relief of osteoarthritis and other ailments of the knee, but a similar infrastructure for the temporomandibular joint is comparatively lacking,” says senior co-author Kyriacos A. Athanasiou, UCI Distinguished Professor of biomedical engineering. “Both joints are essential to a good quality of life, so we would like to see people suffering from TMJ disorders given the same range of options as others have with their knees.”

The knee and TMJ are among the most heavily used joints in the body, and both endure large forces. Light jogging can expose the knee to the equivalent of over four times the body’s weight, and the TMJ can

BME Discovery

experience a force equal to the body’s full weight when biting.

According to the study, about a quarter of adults suffer some sort of cartilage problem, with about 14 percent of U.S. adults afflicted with knee osteoarthritis. Data are not as clear for jaw ailments, but the TMJ Association estimates that a similar number of adults have issues with that joint.

Nonetheless, the researchers calculated a 2,000-fold higher frequency of total knee joint replacements compared to TMJ. In addition, the knee is the focus of six times as many peer-reviewed journal publications and a significantly larger number of federal grants.

In this and other studies, Athanasiou and his group have highlighted the existence of what they call the TMJ gender paradox, in which jaw disorders are four times more prevalent in women than men, and women present more severe symptoms.

“Unfortunately, this gender bias affects the field as a whole,” says co-lead author Benjamin Bielajew, a UCI Ph.D. candidate in biomedical engineering. “Studies have demonstrated that physicians are more likely to recommend pain medication to patients of their same gender. With most oral and maxillofacial surgeons being male, this could lead to women with TMJ disorders not getting the help they need.”

Bielajew says a more equitable approach toward TMJ is also needed for animal studies, clinical trials and patient treatment.

But gender isn’t the only factor behind differences in treatment.

Although the knee and the TMJ share many similarities, their locations in the human body also influence how medicine approaches each, says co-lead author Ryan Donahue, a UCI Ph.D. candidate in

biomedical engineering.

“The TMJ is situated right next to the inner ear, the brain and a complex network of sensory nerves, so naturally any surgical procedures are going to be that much more difficult. However, for the knee, you almost never see damage to surrounding nerves and other leg tissues because of knee surgeries,” Donahue says.

One example the researchers highlighted was a Teflon implant that was approved by the U.S. Food and Drug Administration in the early 1980s.

“It’s one thing for a Teflon surface to deteriorate and distribute particles around the hip joint, but when this happened with the TMJ, near patients’ brains, it led to catastrophic outcomes,” says co-lead author Gabriela Espinosa, a UCI postdoctoral fellow in biomedical engineering. “This resulted in the TMJ field being set back decades when compared to the knee; progress has been stifled even to this day.”

But that was decades ago, and now there are more advanced, naturally inspired engineered tissues that can be used to regenerate worn cartilage in joints throughout the body, including the TMJ, although the latter is only in the development stages at UCI and elsewhere.

“There have been enormous strides in regenerative tissue engineering solutions for the knee in recent years,” Athanasiou says. “Our hope is that success in regenerative medicine for the knee can be used as a template for similar long-term remedies for the TMJ.” This study, which received funding from the National Institutes of Health, also included researchers and clinicians from the University of Texas School of Dentistry in Houston, Harvard Medical School, UC Davis, and private practice.

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STUDENT MERITS

OUTSTANDING TALENT Scholars receive competitive funding to further their research and education

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WENDY BROWN, BIOMEDICAL ENGINEERING POSTDOCTORAL SCHOLAR, HAS BEEN NAMED A 2020 FOR WOMEN IN SCIENCE FELLOW BY L’ORÉAL USA. Brown is one of five female postdoctoral scientists in the country to receive the grant of $60,000.

Working in Distinguished Professor Kyriacos Athanasiou’s lab, Brown focuses on engineering cartilage for facial reconstruction.

Nasal cartilage pathologies (like congenital defects) and trauma have devastating health effects for civilians and military personnel.

Large, mechanically robust grafts are required for reconstructive rhinoplasty and are frequently harvested from a patient’s own nasal septum. However, this is often not possible because the nose is damaged. Brown is working on growing cartilage in anatomical shapes and sizes from highly expanded cells for surgical implantation. She seeks to help millions of people around the world with facial damage.

“This fellowship allows me to establish myself as an independent scientist and to pursue career-defining research in my area of interest,” said Brown. “This fellowship also gives me the resources to serve as a mentor and to develop science outreach programs for other young women in STEM.”

TWO BME STUDENTS RECEIVED GRADUATE RESEARCH FELLOWSHIP PROGRAM AWARDS FROM THE NATIONAL SCIENCE FOUNDATION. The GRFP is a five-year fellowship providing financial support to graduate students for three years. The competitive award is open to master’s and doctoral students who are pursuing STEM-oriented research at accredited U.S. institutions.

ANDREW SUM is a second-year doctoral student. Advised by Associate Professor Elliot Hui, Sum is working on a microfluidic droplet platform for highthroughput screening of a panel of peptides, small protein-like molecules. Sum’s research goal is to screen metagenomic samples for synergistic antimicrobial effects where a combination of two or more peptides would have a greater effect than the peptides would individually. “The discoveries from these experiments can potentially address issues related to antibiotic resistance and agricultural pathogen prevention,” said Sum.

HEATHER ROMERO MERCIECA is a senior undergraduate student. She will pursue her doctorate and conduct research focusing on renewable energy. During her undergraduate studies, Romero Mercieca spent more than two years researching electrochemical sensors in Professor Michelle Khine’s lab. Most recently, she was working with a team to develop an electrochemical aptamer-based biosensor for the detection of SARS-CoV-2. After earning her doctorate, Romero Mercieca hopes to help communities of black, indigenous and people of color attain energy sovereignty.

“It is a great honor to get the NSF Graduate Research Fellowship, as it will give me the financial support to complete my Ph.D. as well as the freedom to define my research focus and goals,” she said. “I would like to thank the Minority Science Program at UCI for uplifting and guiding me through my research and application process.”

On winning the award, Sum said, “It was extremely encouraging to know that other scientists thought my ideas and goals were worth funding.”

UCI Department of Biomedical Engineering

THE ROSE HILLS FOUNDATION HAS AWARDED ONE GRADUATE FELLOWSHIP AND TWO UNDERGRADUATE SCHOLARSHIPS TO BIOMEDICAL ENGINEERING STUDENTS THIS YEAR. The graduate fellow, JOANNE LY, will be granted $10,000, while undergraduate scholars will receive an amount equal to work study and loan amounts.

Ly is working on a technology to help clinicians who care for premature infants in the neonatal intensive care unit. She is creating a device that would monitor preterm infants’ breathing while they are feeding to measure how well they are developing.

“This technology would provide physicians and nurses an objective measurement to support their care recommendations, reduce the number of days preterm infants stay in the neonatal intensive care unit, as well as help hospitals save millions of dollars annually,” said Ly, who is grateful for the fellowship support. “It enables me to focus on my research and devote more of my time to develop programs and opportunities to elevate others, personally and professionally.”

The two undergraduates who received Rose Hills scholarships are Kylie Mae Brown and Luis Gerardo Escalante.

BME Discovery

GRADUATE STUDENT JULIA ZAKASHANSKY IS A 2021-22 UCI ARCS (ACHIEVEMENT REWARDS FOR COLLEGE SCIENTISTS) SCHOLAR. The award recognizes academically superior doctoral students who exhibit outstanding promise as scientists, researchers and leaders.

Zakashansky, materials science and engineering doctoral candidate, is conducting research in biomedical engineering Professor Michelle Khine’s lab to develop a noninvasive at-home antigen test detecting the spike of SARS-CoV-2 proteins in saliva.

The point-of-care platform uses saliva, an electrochemical reaction and Shrinky Dinks to create low-cost electrodes. The device would be paired with a potentiostat, a USB flash drive-sized reader, plugging directly into a phone or tablet with results in approximately 30 minutes. She and Khine have posted their research on medRxiv.org.

Zakashansky said, “What we’ve shown is that we are capable of detecting really low levels of the viral protein, which is promising for the future of accurate detection of early infections as well as infections in asymptomatic people.”

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BME 3 Online Biomedical engineering class popular with students of all majors SHERRY NGO

O

NE OF THE SAMUELI SCHOOL OF ENGINEERING’S LARGEST, MOST POPULAR CLASSES IS FILLED WITH STUDENTS OF MANY DIFFERENT MAJORS.

Engineering Innovations in Treating Diabetes (Biomedical Engineering 3) is an innovative and completely online course taught by James Brody, associate professor of biomedical engineering.

Brody’s goal is to introduce students to the impact of engineering in medicine. He believes that all kinds of students, even those who aren’t interested in becoming an engineer or entering the medical field, can benefit from taking this class.

“Understanding and interpreting medical research and the limitations of medicinal drugs are things that people run into their whole lives,” he says. “What I’m trying to do is get as many people as I can and make sure they have a basic understanding of biomedical science and how to interpret these things.”

BME 3 takes students through the developments and innovations in diabetes treatment. Students learn about purification of insulin, measuring and control of blood glucose, recombinant DNA, clinical trials

UCI Department of Biomedical Engineering

“Although the class

size was tremendous, Professor Brody creates

discussions to actively engage the students in communicating with one another.”

and ethics. They also learn how to solve optimization problems in engineering with Excel. The class fulfills two general education categories: science and technology; and quantitative, symbolic and computational reasoning.

This year, 2021, marks the 100th anniversary of the discovery of insulin, and it was the history behind this finding that inspired Brody to create the class. Before insulin, a diabetes diagnosis was basically equivalent to a death sentence. Patients were expected to live for about two to three years and be bedridden in their last months of life. Following the discovery of insulin in 1921, the first human patient received a dosage of insulin a year later and was able to make a miraculous recovery. “What I’ve done is build a class about biomedical engineering out of that story,” Brody says.

This is the second year he has offered the course, and it has always been taught online, even before the COVID-19 pandemic.

He says the online format brings unique benefits, including accessibility. “The online class allows more people to participate because they’re not constrained by the schedule,” he says. This past winter, 570 students enrolled, a large increase from last year’s 196. There were high numbers of students from other majors, including BME Discovery

60 criminology majors and 74 business economics majors. The class, which is funded by UC’s Innovative Learning Technology Initiative, is open to students from other UC campuses as well.

The class also takes advantage of online tools such as Perusall, which allows students to annotate important texts, propose thoughtful questions and respond to questions from peers. “For discussions, it’s a great way to get students to engage in what we call peer-to-peer learning,” Brody says.

The class feedback reflects the dynamic nature of the course, and student reviews highlighted the class’s engaging material and Brody’s passionate teaching style.

One student wrote, “Professor Brody efficiently organizes and structures the course on a weekly basis to facilitate the access to specific lectures, assignments and quizzes. Although the class size was tremendous, Professor Brody creates discussions to actively engage the students in communicating with one another.”

The class topic, diabetes, is highly relevant to today’s world. People coping with diabetes can be found almost anywhere. “Pretty much everyone knows someone who has Type 1 diabetes, but a lot of times, thanks to insulin, we can’t even tell that a person has it,” Brody says.

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DIRECTORY Zoran Nenadic, D.Sc.

Zhongping Chen, Ph.D.

Anthony Durkin, Ph.D.

William J. Link Chair and Professor of Biomedical Engineering

Professor of Biomedical Engineering, Surgery

Associate Professor of Biomedical Engineering

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

Email: z2chen@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: adurkin@uci.edu

Email: znenadic@uci.edu

Naomi Chesler, Ph.D.

Kyriacos Athanasiou, Ph.D.

Director of the Edwards Lifesciences Center for Advanced Cardiovascular Technology, Professor of Biomedical Engineering

Enrico Gratton, Ph.D.

Email: nchesler@uci.edu

Email: egratton@uci.edu

Distinguished Professor of Biomedical Engineering

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 Email: athens@uci.edu

Michael Berns, Ph.D. 34

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

Distinguished Professor Emeritus, and the Arnold and Mabel Beckman Professor in Biomedical Engineering, Developmental and Cell Biology, and Surgery

Research Interests: photomedicine, laser microscopy, biomedical devices Email: mwberns@uci.edu

Elliot Botvinick, Ph.D. Professor of Surgery, Biomedical Engineering

Research Interests: laser microbeams, cellular mechanotransduction, mechanobiology

Email: elliot.botvinick@uci.edu

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: gjbrewer@uci.edu

James Brody, Ph.D. Associate Professor of Biomedical Engineering

Research Interests: bioinformatics, micro-nanoscale systems Email: jpbrody@uci.edu

Research Interests: cardiovascular mechanobiology and biomechanics; engineering education; diversity, equity and inclusion in STEM

Professor of Biomedical Engineering, Physics and Astronomy Research Interests: design of new fluorescence instruments, protein dynamics, single molecule, fluorescence microscopy, photon migration in tissues

Bernard Choi, Ph.D.

Anna Grosberg, Ph.D.

Professor of Surgery, Biomedical Engineering

Associate Professor of Biomedical Engineering, Chemical and Biomolecular Engineering

Research Interests: biomedical optics, in vivo optical imaging, microvasculature, light-based therapeutics Email: choib@uci.edu

Michelle Digman, Ph.D. Associate Professor of Biomedical Engineering

Research Interests: biophotonics, fluorescence spectroscopy and microscopy, nanoscale imaging, mechanotransduction, cancer cell migration, fluorescence lifetime and metabolic mapping Email: mdigman@uci.edu

Fangyuan Ding, Ph.D. Assistant Professor of Biomedical Engineering

Research Interests: quantitative single molecule biology and engineering, systems biology, nucleic-acid-based therapies, single cell research tool developments Email: dingfy@uci.edu

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

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

Research Interests: computational modeling of biological systems, biomechanics, cardiac tissue engineering Email: grosberg@uci.edu

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

Tibor Juhasz, Ph.D. Professor of Ophthalmology, Biomedical Engineering

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

UCI Department of Biomedical Engineering

Arash Kheradvar, M.D., Ph.D. Professor of Biomedical Engineering, Mechanical and Aerospace Engineering

Ronke Olabisi, Ph.D.

Associate Professor of Biomedical Engineering, Molecular Biology, Biochemistry

Assistant Professor of Biomedical Engineering, Samueli Faculty Development Chair

Email: ccl@uci.edu

Email: ronke.olabisi@uci.edu

Research Interests: orthopedic tissue engineering and regenerative medicine for injury, aging, disease and space flight

Research Interests: cardiac mechanics, cardiovascular devices, cardiac imaging

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

Michelle Khine, Ph.D.

Wendy F. Liu, Ph.D.

Daryl Preece, Ph.D.

Professor of Biomedical Engineering, Materials Science and Engineering

Professor of Biomedical Engineering, Chemical and Biomolecular Engineering

Assistant Professor of Biomedical Engineering

Email: arashkh@uci.edu

Research Interests: development of novel nano- and microfabrication technologies and systems for single cell analysis, stem cell research, in vitro diagnostics

NEWLY PROMOTED

Beth A. Lopour, Ph.D.

Christine King, Ph.D.

Associate Professor of Biomedical Engineering

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

Abraham P. Lee, Ph.D. Professor of Biomedical Engineering, Mechanical and Aerospace Engineering

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

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

Email: mkhine@uci.edu

BME Discovery

Chang C. Liu, Ph.D.

NEWLY PROMOTED

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 biomaterials, cellular and molecular mechanisms of tissue regeneration following surgical reconstruction Email: mauneyj@uci.edu

Thomas Milner, Ph.D. Director of Beckman Laser Institute & Medical Clinic, Professor of Surgery, Biomedical Engineering Research Interests: opticalbased therapeutics and diagnostic imaging, biomedical optics sensors, optical tomography Email: milnert@uci.edu

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

Bruce Tromberg, Ph.D. Professor Emeritus of Surgery, Biomedical Engineering Research Interests: photon migration, diffuse optical imaging, non-linear optical microscopy, photodynamic therapy Email: bjtrombe@uci.edu

Liangzhong (Shawn) Xiang, Ph.D. Associate Professor of Radiological Sciences, Biomedical Engineering

Research Interests: X-rayinduced acoustic computed tomography for in vivo radiation dosimetry & radiology, fast proton-induced acoustic imaging for precision proton therapy, and electroacoustic tomography guided electroporation Email: liangzhx@uci.edu

35

AFFILIATED FACULTY Tayloria Adams, Ph.D. Assistant Professor of Chemical and Biomolecular Engineering

James Earthman, Ph.D. Professor of Materials Science and Engineering; Biomedical Engineering

Baruch D. Kuppermann, M.D. Professor of Ophthalmology; Biomedical Engineering

Alpesh N. Amin, M.D. Thomas & Mary Cesario Chair and Professor of Medicine; Biomedical Engineering; Paul Merage School of Business; Program in Nursing Science

Rahim Esfandyarpour, Ph.D. Assistant Professor of Electrical Engineering and Computer Science; Biomedical Engineering

Young Jik Kwon, Ph.D. Professor of Pharmaceutical Sciences; Biomedical Engineering; Chemical and Biomolecular Engineering; Molecular Biology and Biochemistry

Email: tayloria@uci.edu

Email: anamin@uci.edu

Herdeline Ardona, Ph.D. Assistant Professor of Chemical and Biomolecular Engineering Email: hardona@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

Kevin Beier, Ph.D. Assistant Professor of Physiology and Biophysics, Biomedical Engineering Email: kbeier@uci.edu

36

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

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

Email: earthman@uci.edu

Email: rahimes@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: bdkupper@uci.edu

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

Email: zguan@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

Gultekin Gulsen, Ph.D. Associate Professor of Radiological Sciences; Biomedical Engineering; Electrical Engineering and Computer Science; Physics and Astronomy

Han Li, Ph.D. Associate Professor of Chemical and Biomolecular Engineering

Email: rfrostig@uci.edu

Zhibin Guan, Ph.D. Professor of Chemistry; Biomedical Engineering

Email: ggulsen@uci.edu

Email: gpli@uci.edu

Email: han.li@uci.edu

Ranjan Gupta, M.D. Professor of Orthopaedic Surgery; Anatomy and Neurobiology; Biomedical Engineering

Jack Lin, M.D. Professor of Clinical Neurology; Biomedical Engineering

Frank P. Hsu, M.D. Department Chair and Professor of Neurosurgey; Biomedical Engineering; Otolaryngology

Ken Lin, M.D. Associate Clinical Professor of Ophthalmology

Email: ranjang@uci.edu

Email: fpkhsu@uci.edu

Email: linjj@uci.edu

Email: linky@uci.edu

Lan Huang, Ph.D. Professor of Physiology & Biophysics; Biomedical Engineering

John Lowengrub, Ph.D. UCI Chancellor’s Professor of Mathematics; Biomedical Engineering; Chemical and Biomolecular Engineering

Christopher Hughes, Ph.D. Professor of Molecular Biology and Biochemistry; Biomedical Engineering

Ray Luo, Ph.D. Professor of Molecular Biology and Biochemistry; Biomedical Engineering

James V. Jester, Ph.D. Professor in Residence, Ophthalmology; Biomedical Engineering

Marc J. Madou, Ph.D. UCI Distinguished Professor of Mechanical and Aerospace Engineering; Biomedical Engineering; Chemical and Biomolecular Engineering

Email: lanhuang@uci.edu

Email: cchughes@uci.edu

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

Email: jlowengr@uci.edu

Email: rluo@uci.edu

Email: mmadou@uci.edu

John Middlebrooks, Ph.D.

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

UCI Department of Biomedical Engineering

Sabee Molloi, Ph.D. Professor of Radiological Sciences; Biomedical Engineering

Zuzanna S. Siwy, Ph.D. Professor of Physics and Astronomy; Biomedical Engineering; Chemistry

Jogeshwar Mukherjee, Ph.D.

Ramesh Srinivasan, Ph.D. Professor of Cognitive Sciences; Biomedical Engineering

Email: symolloi@uci.edu

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

Brian Paegel, Ph.D. Professor of Pharmaceutical Sciences, Biomedical Engineering Email: bpaegel@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

Terence Sanger, M.D., Ph.D. Professor of Electrical Engineering and Computer Science, Biomedical Engineering Email: tsanger@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

Seunghyun Sim, Ph.D. Assistant Professor of Chemistry; Biomedical Engineering Email: s.sim@uci.edu BME Discovery

Email: zsiwy@uci.edu

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 Biomolecular Engineering 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

Zhuoli Zhang, M.D., Ph.D. Professor of Radiology Email: zhuoliz1@uci.edu

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

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 Nicolaos Alexopoulos Broadcom Foundation Vasudev Bailey Quid Thomas Frinzi Johnson & Johnson Vision Thomas Burns Glaukos Corp.

David Bardin Glaukos Corp.

37

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Department of Biomedical Engineering

PAID 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

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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, select Biomedical Engineering.

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