Among these cancers is triple negative breast cancer (TNBC). What makes TNBC so aggressive and hard to treat is that the cancer cells in TNBC lack three things found in many other breast cancers: an estrogen receptor, a progesterone receptor, and extra receptors for a protein called HER2. As a result, the cancer does not respond to breast cancer treatments that target these receptors. TNBC accounts for about 10 to 15 percent of all breast cancers.

The team, led by UC San Diego bioengineering professor Shankar Subramaniam, will perform fundamental studies to decipher the precise pathways involved in TNBC initiation, progression and metastasis. The researchers will use innovative experimental approaches, multi-omics strategies and data analytics to delineate these pathways and develop robust models of TNBC. Their work could potentially help identify stage and etiology-specific next generation therapeutics for TNBC.

Karios took $155,000 home. More than 50 companies were part of the event’s first round, and only six made it to the finals, which took place in late March 2022.

The company is commercializing a hydrogel that forms a barrier to keep heart tissue from adhering to surrounding tissue after surgery. The hydrogel was successfully tested in rodents by a team of University of California San Diego researchers. The team of engineers, scientists and physicians also conducted a pilot study on porcine hearts, with promising results.

Karios Technologies is licensing the technology from UC San Diego. “We are excited to be working to address this large unmet need in cardiac surgery–and other surgeries,” said Gregory Grover, CEO, Co-Inventor, and Co-Founder of Karios Technologies. "Innovation is needed in this space and would have a significant and positive impact on patients, specifically the lives of young children with cardiac anomalies who require multiple life saving surgeries.”

In rats, the hydrogel prevented the formation of adhesions altogether. In a small pilot study, porcine hearts treated with the hydrogel experienced less severe adhesions that were easier to remove. In addition, the hydrogel did not appear to cause chronic inflammation.

Adhesions--organ tissue sticking to surrounding tissue--are a relatively common problem when surgeons need to operate again at the same site, which happens in 20 percent of cases every year in cardiac surgery. Re-operations are particularly common when the patients are children suffering from cardiac malformations--as the child’s heart grows, additional interventions are needed.

Adhesions form within the first 30 days post-op and can complicate operations and increase the risk of mortality during interventions. In some cases, they can also interfere with proper heart function or completely prevent a repeat surgery. UC San Diego bioengineering professor Christman experienced this when one of her uncles couldn’t have a heart valve repaired because of severe adhesions.

“Our work is an engineering solution driven by a medical problem,” said Christman. “And now it’s poised to significantly improve cardiac surgery, both for adults and children.”

Instead of sending a catheter into a patient’s heart to localize the source of the arrhythmia, the new vMap technology requires only data from a standard noninvasive 12-lead electrocardiogram (ECG) – performed in most clinical and ambulatory settings – to create a three-dimensional interactive map of arrhythmia source locations in all four chambers of the heart.

The researchers used computational modeling to create over one million simulations of different heart arrhythmias. The patient’s ECG recordings are compared to this simulation database to accurately locate the source of the arrhythmia.

vMap was invented by bioengineers and cardiologists from UC San Diego, and has been developed by Vektor Medical, a startup co-founded by Professor of Bioengineering, Andrew McCulloch; Professor of Medicine and electrophysiologist, Dr. David Krummen; Assistant Professor of Medicine, electrophysiologist, and bioengineering alumnus, Dr. Gordon Ho; and bioengineering alumnus Dr. Christopher Villongco, Vektor’s chief technology officer. The Vektor Medical team presented their clinical trial results at the Heart Rhythm Society meeting in San Francisco.

Pinpointing an electrical fault

The current standard of care for treating heart arrhythmias – any type of irregular heartbeat that is too fast, too slow, or mistimed due to an electrical signal misfiring – is to carefully burn or freeze the exact spot in the heart where the electrical misfiring is coming from. This procedure, called an ablation, resets the electrical signals and heartbeat. Hundreds of thousands of ablations are performed in the United States every year. But before an electrophysiologist can perform an ablation, they need to know precisely where in the heart the arrhythmia is coming from.

“Mapping is critical to planning and performing ablation. The current process of arrhythmia localization relies upon invasive catheter mapping” said Dr. David Krummen. “It generally works well, but the process can be time consuming, increasing fluoroscopy and anesthesia exposure for the patient. Moreover, occasionally the catheter-based process may "bump" the arrhythmia source and suppress the clinical arrhythmia, preventing further mapping.”

“We wanted to find a way to pinpoint the arrhythmia source location using data from the 12-lead ECG,” he added. “The 12-lead ECG is used in a variety of clinical settings outside the electrophysiology laboratory including the emergency department, the intensive care unit, and the outpatient clinic. One of the major goals of the system is to leverage arrhythmia data from these ECGs to potentially allow arrhythmia source mapping prior to arrival in electrophysiology lab.”

The computational solution

That’s where bioengineering Professor Andrew McCulloch and Christopher Villongco, a PhD student in McCulloch’s lab at the time and now Vektor’s CTO, came in. McCulloch has spent the last 35 years at UC San Diego making models of the heart, from the biochemistry and physiology of its cells and the mechanics of its muscle fibers to the electrical rhythms of the whole heart. His cardiac computational modeling software, Continuity, allows researchers to accurately simulate the heart down to the cellular level. Villongco and McCulloch originally set out to develop personalized computational models to help patients and physicians predict the outcome of certain heart procedures, but soon hit a stumbling block: how to translate computational modeling from academic use to real-time, actionable clinical use?

“Developing detailed, personalized models for individual patients was appropriate for our research at the time, but the process of creating a single model requires a lot of high-quality clinical data, computational power, time, and modeling expertise,” said Villongco. “We learned from collaborating with Drs. Krummen and Ho that the actual clinical demands were quite the opposite: minimal data, limited computational power, rapid analysis, and ease of use in the existing clinical workflow.”

Andrew McCulloch, a professor of bioengineering and Shu Chien Chancellor’s Endowed Chair in Engineering and Medicine, has spent the last 35 years at UC San Diego modeling the heart.

Learning from the collaboration, the team realized they needed to create a massive library of computational models of arrhythmias.

Then the challenge became how to create a model library, when it took a powerful computer cluster several days to create just one model? Combining computationally efficient modeling methods with modern-day computing architectures and resources, a library of over one million arrhythmia simulations was created in just under one year, a vast improvement from the tens of thousands of years it would have otherwise taken. The clinical product was then designed and implemented according to the needs and experiences of electrophysiologists.

The initial research was funded by grants from the NIH, a Jacobs School of Engineering entrepreneurship program, and the Galvanizing Engineering in Medicine program. Then, thanks to funding from the NIH-backed Center for Accelerated Innovation – intended to help transfer technologies from the lab to the clinic – the researchers and Vektor team were able to further hone the tool, expand its capabilities, and test its accuracy. A multicenter, blinded clinical trial showed that in 255 arrhythmia episodes from 225 patients, the vMap tool had a regional accuracy of 96.9%, with a spatial accuracy of 15mm. The median time to complete the mapping process was 48 seconds.

“It’s one thing to make fancy simulations, but it’s altogether another to make something that can be used in the pressure of a clinic, in a matter of minutes, that’s reliable,” said McCulloch. “And we’ve shown that vMap meets all these needs.” McCulloch is also the director of the UC San Diego Institute for Engineering in Medicine, and the Shu Chien Chancellor’s Endowed Chair in Engineering and Medicine.

vMap is a tool for physicians to better understand seven important and often dangerous arrhythmias – ventricular tachycardia; premature ventricular complex; ventricular fibrillation; focal atrial tachycardia; premature atrial complex; orthodromic atrioventricular reentrant tachycardia; and atrial fibrillation. The information vMap provides is intended to increase the success rate for patients undergoing these ablation procedures.

vMap is currently in use by physicians at UC San Diego Health with the intent to reduce ablation procedure times and increase ablation success rates for patients with these seven arrhythmias.

Disclosure: Andrew McCulloch, Ph.D. is a professor of bioengineering at UC San Diego Jacobs School of Engineering. Dr. McCulloch is an inventor of vMap and has equity as a co-founder and Scientific Advisory Board member to Vektor Medical, Inc.

David Krummen, MD, is a cardiac electrophysiologist at UC San Diego Health and professor of medicine at UC San Diego School of Medicine. Dr. Krummen is inventor of vMap and has equity as a co-founder and clinical advisor to Vektor Medical, Inc.

What do you teach?

I’ve been teaching for 51 years – high school math (I’m certified in New York); at an experimental elementary school in Blacksburg Virginia; 6 years as a TA at Cornell; university professor ever since.

For 6 years I was the chief advisor to 1600 electrical engineering students at Illinois– one of my students is now a UC San Diego Bioengineering faculty member; I founded the Bioengineering Department at Illinois and created its bachelors, masters, and PhD programs –two of my first faculty hires are now my colleagues in the UC San Diego Bioengineering Department; I also created the bachelor’s degree program in Biomedical Engineering at the University of Florida while I was Department Chair. For the last six years I have taught every graduating senior in the Bioengineering senior design course.

What do you enjoy about teaching?

Seven years ago I came to UC San Diego for two reasons – to help with the start of the Biosystems major – apparently someone thought I knew something about starting bioengineering degree programs -- and because, as my beard and hair grew increasingly gray, I thought that I would have greater impact not from another R01 grant but rather by communicating my experiences to and working with undergraduate students.

This award says that I made the right choice. My dream has been fulfilled.

Why is teaching an important, integral part of your job?

It has been a most wonderful experience, being surrounded by incredibly bright, driven, personable, innovative people – with very diverse interests and backgrounds. They will shape the future of our state and our nation. I’m proud of all of them.

I’ve had the opportunity to encourage many to see a future beyond what they imagined when they entered UC San Diego. My students have kept me young – perhaps the greatest gift that anyone could ever get. They have given me far more than I have given them. I am most grateful. Thanks so very much to my loving and supportive family: my wife Gayle and daughters Jean and Julie – all biomedical engineers or biomedical practitioners; to the Bioengineering Department, to the Jacobs School, and to UC San Diego. Thanks to Adam Engler who nominated me and to students who supported me with letters.

Professor Silva is the Founding Director of the Center for Engineered Natural Intelligence, and Associate Director of the Kavli Institute for Brain and Mind. He is a full Professor at UC San Diego Bioengineering and is an affiliated faculty member in the Department of NanoEngineering, and a faculty member in the BioCircuits Institute, the Neurosciences Graduate Program, Computational Neurobiology Program, and Institute for Neural Computation. In addition to his academic work, he has written popular press articles for a number of magazines, including Elemental, The Startup, Cantor’s Paradise, and BeingWell. He is also a regular contributor to Forbes (Mathematical Neuroscience Lab, http://www.silva.ucsd.edu/silvabio). This Endowed Chair appointment is a testament of Professor Silva’s stellar record and serves to support and advance further his teaching and research at UC San Diego.

Chair Engler and the scientific community celebrates Dr. Silva for this outstanding achievement.

Dr. Christman is a Full Professor in the Department of Bioengineering. She is a member of the UC San Diego Institute of Engineering in Medicine and the Sanford Consortium for Regenerative Medicine. Her record is outstanding in multiple dimensions and has an exceptional record of outstanding contributions to basic and translational science, bioengineering and medical innovation, service to the department, campus and profession, teaching at all levels and contributions that promote diversity. More on Dr. Christman's legacy and stellar record is found at http://christman.eng.ucsd.edu/people.

The Galletti legacy emphasizes the clinical and engineering translation of innovations in bioengineering science. Professor Bruce Wheeler, commented that “Dr. Christman’s record clearly addresses this, as she has developed – from basic science to application – research findings and novel technology that has become a serious contender for a new biomaterial therapies for treating widespread and serious medical conditions”.

Chair Engler and the scientific community celebrates Dr. Christman for this outstanding achievement.