Sorace receives R01 from NCI to study immunotherapy in HER2+ breast cancer through Imaging

New UAB research is combining mathematical modeling and advanced imaging to find the right mix of therapy for patients with a common subtype of breast cancer.

In fiscal year 2019, UAB researchers received a record $602 million in grants and contracts, marking a second year of double-digit percentage growth in funding. That productivity has carried on unabated in 2020, and you can follow along. Every Tuesday, Research Administration releases a list of the grants and contracts awarded the previous week (BlazerID required).

In this new series, we’re spotlighting new or re-funded projects to offer a window into the groundbreaking, lifesaving work done by our colleagues around campus. (See other stories in this series, profiling grants to accelerate HIV suppression, test a new strategy against lupus, stop online opioid sales and build freezers for the International Space Station.)

This week, we’re taking a look at a project to make breast-cancer therapy more precise using mathematical modeling and advanced imaging.

Project title: Personalizing Immunotherapy in HER2+ Breast Cancer through Quantitative Imaging

Principal investigator: Anna Sorace, Ph.D., departments of Biomedical Engineering and Radiology; co-investigators Erica Stringer-Reasor, M.D., Division of Hematology & Oncology, Jonathan McConathy, M.D., Ph.D., Department of Radiology, Jianmei Leavenworth, M.D., Ph.D., Department of Neurosurgery, Yufeng Li, Ph.D., Division of Preventive Medicine at UAB and Thomas Yankeelov, Ph.D., and Carla Van Den Berg, PharmD, at the University of Texas-Austin.

Funding: Four years, $1.63 million from the National Cancer Institute

rep dod sorace 413x550 Anna Sorace, Ph.D.About 25% of breast cancers are driven by a mutation in the protein human epidermal growth factor receptor 2 (HER2). As the name suggests, HER2 promotes cell growth, and women with this form of breast cancer produce abnormally high levels of the protein. HER2-positive cancers tend to be more aggressive than other breast-cancer types. Treatments that target HER2 — such as trastuzumab (Herceptin) and pertuzumab (Perjeta) — are very effective for many patients, but “there are still about 50% of patients who do not have a complete response to these therapies,” said Anna Sorace, Ph.D., an assistant professor in the departments of Radiology and Biomedical Engineering, and an associate scientist in the O’Neal Comprehensive Cancer Center.

Immunotherapy treatments, including checkpoint inhibitors such as anti-PD1 and anti-PD-L1, hold promise to improve those percentages when used in combination with targeted therapies. Determining the best sequencing, dosing and timing of the combinations for each patient is no trivial matter, however. “There are essentially an infinite number of combinations,” Sorace said. And the answer is liable to be different depending on the patient. “Every tumor is different,” she explained. Part of the difference lies in the specific genetic changes driving the cancer, but “also due to the tumor’s vasculature and surrounding microenvironment,” Sorace said.

“This work really bridges a gap between engineering, imaging science, cancer and hopefully drives forward into clinical translation in the future.”

There are so many combinations that finding the optimal fix is not “something we can test in clinical trials or even solely in animal models,” Sorace said. So her team has developed a mathematical model describing HER2 response to targeted therapies that enables them to identify the best potential combinations in silico before they are tested in animal models and then translated to patients.

With a new R01 grant from the National Cancer Institute, Sorace is “extending that model to include more information on immune cell changes in response to immunotherapy to identify how to best guide these combination therapies.” As part of the work, she is tapping in to the imaging capabilities in UAB’s Small Animal Imaging Facility and Cyclotron Facility, including preclinical PET and MRI scanners and translational radiopharmaceuticals. “This work is heavily dependent on the quantitative information that we can extract from advanced imaging,” Sorace said. “We’re able to combine anatomical and functional information” about the tumor and its vasculature, as revealed by MRI, with “ information on changes in the tumor’s microenvironment — such as the amount of hypoxia, or lack of oxygenation in the tumor,” which is the domain of PET imaging.

“This work really bridges a gap between engineering, imaging science, cancer and hopefully drives forward into clinical translation in the future,” Sorace said.

Opportunities to collaborate

Sorace added that she is open to new collaborations in diverse fields. “I am always looking for people who are interested in introducing imaging into their cancer biology studies, whether they are getting close to clinical translation or working on understanding fundamental cancer biology,” she said.

More News

Mansur awarded a TL1 fellowship to study health disparity in HER2-positive breast cancer patients

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Ameer Mansur, a Ph.D. candidate in the laboratory of Anna Sorace, Ph.D., assistant professor in the UAB Department of Biomedical Engineering, has been awarded a pre-doctoral research training program (TL1) fellowship from the UAB Center for Clinical and Translational Science (CCTS), for his project, titled, “Prognostic biometric extraction of multiparametric imaging data in human epidermal growth factor receptor (HER2) positive breast cancer.” The fellowship is effective July 1, 2023 and will run through July 2024.

Feldman retires after nearly four decades at UAB

After a career spanning nearly 40 years at UAB in the Department of Biomedical Engineering, Dale Feldman, Ph.D., associate professor, officially retired on May 31, 2023. This is not, however, the conclusion of his long and productive career. Feldman emphasizes that he will continue to assist the department with accreditation for undergraduate education, and to teach two of the three required courses for the Translation of Biomedical Innovations to Clinical Practice certificate program.

UAB Goldwater Scholars announced for 2023

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Stevenson awarded NIH internship to study acoustophoresis in cell washing

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Biomedical Engineering student Emma Stevenson has been awarded a 10-week Biomedical Engineering Summer Internship from the National Institute of Health’s Institute of Biomedical Imaging and Bioengineering (NBIB) for her project titled, “Automation of radioactive cell labeling using microfluidic acoustophoresis.” The NBIB summer internship allows rising biomedical engineering students to participate in cutting-edge research projects under the mentorship of world-class scientists in NIH laboratories in Bethesda, Maryland, from June 5 to August 11, 2023.

Co-op program creates a pipeline into a growing industry

BioHorizons is a Birmingham company whose history is rooted in UAB. Today, thanks to a growing and successful co-op program, it appears that BioHorizons and UAB will continue to be linked far into the future.

The dental-implant company, which started as a spinoff of research from the UAB Schools of Engineering and Dentistry, has hired more than a dozen UAB alumni and students over the past 28 years. More recently, though, its co-op program has begun to bring in current engineering undergraduates—creating a talent pipeline for students to get a head start in a growing industry.

“Hands-on experience has always been a key element of engineering education,” said Neil Adams, director of the Engineering Career Center. “The success of our program depends on strong co-op and intern partners, like BioHorizons, who offer quality experiences to our students so that they apply their engineering knowledge while also learning how to be a contributing part of a professional organization. We are proud of this continued partnership and look forward to supporting Blazer engineering co-ops at BioHorizons for many years to come.”

A Blazer Legacy

BioHorizons was started in 1995 by the late Martha Bidez, Ph.D., then a faculty member in the School of Engineering who would serve as the company’s first CEO before selling the company and returning to UAB in 2009. Over the years, the company has hired a number of UAB alumni, including several members of its leadership team (see sidebar).

In 2016, however, the company’s ties to UAB got a little closer when Ashley Boggs became the first UAB undergraduate to join the BioHorizons co-op program—a program that provides students the opportunity to work full-time at the company for three semesters, alternating with school. The experience is paid, and students work alongside engineers throughout their time at the company.

Boggs extended her co-op by working part-time at the company until she was hired full time after she graduated in 2018. Today, she is a Digital Dentistry Engineering Manager, and she credits her co-op experience for opening her eyes to possibilities she had never previously considered.

“I had a vague idea that I wanted to work with implants—like hips, knees, ankles—but I didn’t know anything about the dental-implant industry at all,” said Boggs. “During my sophomore year, I went to the Engineering Career Center and told them that I couldn’t keep sitting in class doing problems from a book. They told me about a local company called BioHorizons that was doing on-campus interviews.”

The interview changed Boggs’s personal career trajectory, but her story is not an unusual one. While the engineering curriculum prepares students for a wide variety of careers, it’s often that first on-the-job experience that opens eyes and doors to career opportunities in fields students may have never been aware of.

That was the case for UAB graduate Jonathan Gordon, another former co-op participant who now works as a packaging engineer for BioHorizons. “I started out on a pre-med track, but coming from a very small town to UAB was a big transition,” Gordon said. “I dropped the pre-med route pretty quickly and started looking for other options.”

Like Boggs, the Engineering Career Center helped connect Gordon with a co-op position at BioHorizons, and that, in turn, led to full-time employment. “I realized pretty quickly that I love this industry. It’s exciting to be a part of this.”

An Undergraduate Pipeline

Although Boggs was the first UAB student hired into BioHorizons' co-op program, she soon had company. Three other Blazers followed her into the program (Josh Moore, Karly Casey and Gordon), and all four stayed on to work full-time. That kind of retention is notable for an undergraduate experience that by its nature is often exploratory.

“Since we started the co-op program about 10 years ago, we have had about 17-18 engineering students in our program—two of which have been in our regulatory department and the rest in research and development,” said Tom Lewis, BioHorizons manager of product engineering. “We feel that it has been very successful, and to date we have hired five as full-time employees.”

That transition from co-op to full-time employee makes sense when you consider the investment BioHorizons makes in students over a three-semester co-op. Each student must learn Quality System processes before getting down to work with tasks, such as design control, drawing release, and CAD modeling. “Each student is trained, but it takes hands-on involvement to learn all of these processes,” Lewis said. “It’s also helpful for students to experience how different departments work together for a common goal.”

In addition, students must learn industry standards and technologies in the medical device industry. “This takes longer,” Lewis said, “but over time they begin to understand the ‘whys’ behind the design of dental implants, restorative components and instruments. Although we have the expectation that co-ops produce for us, my hope is that when they look back they realize the value of their experience here, and as they move into their careers they have a head start in their understanding of engineering organizations."

“Co-op is both an investment by the company and a commitment by the student,” added Adams. “The depth of experience pays dividends in that co-op students are ready to contribute immediately at an organization after graduation.”

“I have been part of teams in which we have drawn and developed state of the art dental surgery kits that are slated to hit the market this year; I have managed drafting and conducting test plans to research the durability of implant designs; and, most importantly, I have been able to teach incoming co-ops the ins and outs of the company and guide them as they grow from a college student into true engineers.”
—Benjamin Pody, mechanical engineering student and 2nd-year co-op

Homegrown Talent

Lewis says the co-op program historically has drawn from several area universities, but he admits UAB students have one obvious advantage. “Since they are local, they already have living arrangements,” he said. “After completing the three co-op terms, students return to school to finish up and graduate. With UAB being in town, when the opportunity was available several UAB students have stayed on and worked part-time until graduation. The company knowledge they have has allowed them to be productive even on a part-time basis.”

While the growth of BioHorizons’ co-op program is exciting for current and future engineering students, UAB School of Engineering Dean Jeff Holmes, M.D., Ph.D., says that is just one of the reasons UAB engineers should look at the BioHorizons story with pride.

“It’s not unusual for a promising startup to spin off from university research—in this case, arising from research in the UAB Schools of Engineering and Dentistry,” said Holmes. “We often comment that these startups have the potential to revolutionize an industry. But in the case of BioHorizons, it has actually done that, and it continues to innovate and to grow. I am tremendously excited that our students are able to be a part of that continuing UAB success story.”

“At BioHorizons, we look forward to continuing our work with UAB in the future,” agreed Lewis. “We appreciate the relationship we have developed with the university that has served us well over the years.”