Creating a Network of Cancer-Fighting Researchers

Researchers have been looking for ways to fight cancer for decades. Often, extraordinary leaps in advancement are brought about by team efforts. NCSA’s Health Innovation Program Office (HIPO) exists in part to create and foster these types of large collaborative efforts within the healthcare sphere. Recently, HIPO directed its efforts to bring together researchers working toward a better pancreatic cancer treatment, and the research has shown promising results.

Stephen A. Boppart is the principal investigator (PI) on a project conducting research on innovative ways to treat pancreatic cancer more effectively. Boppart is not only a professor here at the University of Illinois in Urbana Champaign (UIUC). Among his many titles, he also holds a Grainger Distinguished Chair in Engineering and is the Illinois Director of the Mayo Clinic & Illinois Alliance for Technology-Based Healthcare. At the intersection of several disciplines, Boppart is in a unique position to see how collaborative efforts can produce amazing results.

Boppart’s team wanted to find faster ways to treat pancreatic cancer, one of the deadliest forms of cancer. The combined five-year survival rate of pancreatic cancer – meaning the average of all patients who are diagnosed with pancreatic cancer at any stage – is extremely low. Only five to ten percent of patients survive five years. Part of the reason for this low average is that most patients aren’t diagnosed until they reach stage IV. It’s hard to find this cancer, in part because of where the pancreas is located, deep within the body, but also because this type of cancer rarely causes symptoms at an early stage, and it progresses very quickly. Many of the symptoms are also commonly caused by other ailments, further complicating finding it.

Because of the deadly nature of this cancer and how quickly it grows, it’s all the more important to find treatments that work quickly and efficiently. This is the crux of the problem that Boppart’s team is working to resolve. “Our study was looking to find new optical signatures from living tissues and cells that would indicate earlier whether a human pancreatic tumor was responding to chemotherapy or not,” Boppart said. “We had developed and utilized a new label-free multi-modal imaging technology that gave us information about the structure, molecules, metabolism, and function of the cells and from these optical measurements, we could detect changes earlier. For this study, we used a common model by which we transplanted human pancreatic tumor cells from living patients into living mice so that our experiments and testing can be done on the mice as the human tumors either responded or were resistant to the chemotherapy.”

Chemotherapy is a tricky bit of medicine. Cancer has many faces – even cancers of the same type respond very differently to a specific chemotherapy medicine, of which there are hundreds of combinations doctors can use to treat patients. Janet Sorrells also worked on Boppart’s team. She’s a graduate student in bioengineering, and she explains the difficulty of treating pancreatic cancer. “Generally, it’s hard to predict how an individual’s pancreatic tumor will respond to a given chemotherapy combination,” she said. “and there is a need to better understand the biochemical mechanisms of chemotherapy resistance and better ways to noninvasively screen tumor drug response.”

There isn’t really a one-size-fits-all solution for certain cancers, pancreatic among them. With time of the essence, doctors need to quickly find what chemotherapies work best for their patients before they lose the battle to the cancer they’re treating. Research like Boppart’s, which was published in Nature Communications Biology, is essential to quickly finding the exact concoction of chemicals that will work the best.

“This work sets the stage for future work in personalized medicine in cancer,” said Sorrells. “Tumors can be very diverse, and especially in diseases like pancreatic cancer, it can be deadly if an ineffective chemotherapy regimen is chosen. With biological systems like patient-derived xenografts in mice and organoid models and with advanced imaging technologies like ours, we can hopefully provide relatively fast feedback on what drugs will be the most effective in treating a specific tumor.”

This research could be life-changing for pancreatic cancer patients. “We believe this work is highly significant and impactful,” said Boppart. “If we are able to detect and determine whether a specific chemotherapy drug is effective in a patient’s living tumor, and do so rapidly, then we would know which chemotherapy to use right away in the patient, without the guesswork and loss of time after trying different chemotherapies to find out which would work to help the patient.”

This type of research has a lot of moving pieces and requires an interdisciplinary set of experts to tackle. Finding the right experts is an important aspect of a successful research outcome. Often, researchers work in parallel with each other on separate projects without knowing about each other’s work until it’s published. Researchers in completely different research domains might also benefit from being brought together to solve a common problem between the two. Colleen Bushell, director of HIPO, knows that sometimes, when you bring two projects together, the results can be phenomenal. This is, in essence, what HIPO does best. It’s an office filled with individuals who know how best to connect people to improve results.

“We have people on our team, such as Maria Jaromin, assistant director of research, and Alaina Kanfer, assistant director of strategic partnerships, that have a lot of experience and years of success –not only in establishing connections but also shepherding these relationships and taking an active role in acquiring funding to support the new collaborations,” said Bushell. “Once funding is established, we have an incredible team led by Holly Highland, assistant director of operations, to oversee the logistical and financial aspects of the project.” 

While the research being conducted at Mayo and at UIUC wasn’t identical, Bushell could see that it was highly complimentary. Bushell and her team work as a kind of research matchmaker. They keep abreast of the research being conducted at various organizations, and when HIPO hears about intriguing new research from Mayo, for instance, they can match them up with a researcher at another organization to leverage overlapping expertise.

In this case, Bushell knew there were Mayo surgeons and researchers working with mice – specifically, growing human tumors in mice to find ways to treat cancer. Bushell became aware of Boppart’s work and immediately knew the two groups could benefit from working together.

“I already had a relationship for many years with Heidi Nelson, then head of surgery at Mayo,” said Bushell. “Through our discussions over the years and other projects we’d worked on, she knew about the unique areas NCSA specializes in. For example, we’ve worked on developing software tools and data analysis with her before. I knew of Boppart’s work, but I hadn’t worked directly with him before. Then, I attended a presentation he and his team gave on their work – the technology they were developing and what they hoped to do. They were working specifically with breast cancer samples, but I could see there was enough overlap that I wanted to try and bring these two together.”

This example is a perfect distillation of what HIPO brings to the table. When Bushell eventually connected Boppart and Nelson, the project began taking off. More researchers joined – pancreatic cancer researcher and surgeon Mark Truty at the Mayo Clinic, NCSA AI and UI/UX experts and faculty who specialize in deep learning were added to the effort. A proposal was drafted by Bushell and Boppart, and funding was acquired to launch a seed project, HIPO assisting with connections all along the way.

Finding similarities between projects in the same research domain seems obvious, but HIPO also specializes in the not-so-obvious, like bringing together two different research domains. “HIPO also identifies overlap with research being conducted at NCSA between science domains,” said Bushell. “In this example, we brought in our colleagues in atmospheric science because we knew they were facing similar challenges in analyzing their satellite images. Bringing together domains not only benefits those researchers, it helps NCSA identify where new technologies can be developed to address common barriers faced by multiple research areas that rely on advanced data science and computation.”

There are other beneficial aspects to working with HIPO besides the deep bench of experts they can link you to. Bushell’s team at NCSA has a strong understanding of how the Center’s resources could help propel a project like this along. Working with HIPO means researchers benefit from all NCSA has to offer as well. Along with the vast array of experienced technical experts and engineers, NCSA houses a diverse group of researchers, data scientists and specialists in the field of visualization. This type of expertise is essential to creating a robust and agile methodology for identifying and treating cancer.

Boppart’s project utilized NCSA’s extensive knowledge in the areas of visualization and image analysis through machine learning. “I believe the expertise and capabilities at NCSA are enormous and enabling,” said Boppart. “Our imaging data is highly multi-dimensional and rich in information. Assistance from the HIPO would be key to helping extract what data and information is most useful for medical decision making.”

“HIPO brought in the AI and UI/UX experts from NCSA that worked with Boppart’s team to develop and evaluate analytical approaches,” said Bushell. “We also developed a prototype software tool to assist in complex image analysis tasks.”

Lisa Gatzke, who leads NCSA’s UIX design team, explained her team’s part in the project. “While working on Boppart’s project, we discovered there was a dearth of tools for doing the initial image annotation to train the models. So, we started working on our own tool. PixSure is purpose-built to improve the speed and accuracy of image annotation for classification models. Image annotation is a necessary but extremely repetitive, monotonous task. The overarching design goal was to facilitate the task by any means we could imagine, including inventing new user interface and user experience techniques where we carefully considered proximity of information to the task, mousing distances, keyboard interactions etc., as well as other input devices like game controllers. The design also planned for integrated machine learning models that would eventually suggest to the user annotations that could be accepted or rejected. Information that, of course, would feed back into the model.”

By finding these varied research experts, connecting them with each other and providing them with NCSA expertise to benefit the project, HIPO was able to help create fertile ground for Boppart’s team.

“Because we had such a large and diverse team,” explained Sorrels, “we were able to examine the problem from many different perspectives: clinical, computational, biological, statistical, and more. This helped us to best utilize all of our data and to consider the broad implications of the study.”

Boppart’s team was successful in proving their methodology would work, but more importantly, their plan is to continue to refine these techniques to make them even faster. As Boppart explains, “In this study, we demonstrated and used our novel imaging approach. We evaluated this imaging in a standard process whereby human tumor cells are implanted into mice, called patient-derived xenografts (PDX). Still, it required several weeks for the tumors to grow in the mice before we imaged them. In the future, we plan to explore how the patient’s tumor cells can be grown into ‘tumor spheroids’ or ‘organoids’ – a mass of cells – and then we can administer the chemotherapy to this mass of cells and image. This would eliminate the need for transplanting into mice and the wait for that tumor to grow. We believe we can make a response/resistant determination even earlier with this approach.”

Sorrells highlighted the ways their team’s approach could help in adjacent research as well. “We have a variety of different future and ongoing projects related to cancer imaging,” she said. “Our lab has created a variety of label-free microscopy systems that can be used to characterize structural, functional, and biochemical aspects of tissues, which are especially useful for looking at cellular metabolism. Dysregulated cellular metabolism is one of the key hallmarks of cancer, so our systems lend themselves well to cancer-related imaging. Our current projects range from diagnostics/screening to drug response characterization to basic science studies looking at mechanisms of the tumor microenvironment.”

HIPO’s role will continue to be one of fostering and curating this work as it moves forward. “Creating solutions like these, creating these types of technologies and advancements, takes a long time,” Bushell said. “HIPO will continue to support the project, creating new connections and contributing to proposals to benefit the long-term goals of the project. The ideal for us at HIPO is to create long-term relationships with the movers and shakers in these domains so that we can continue to help translate important research into clinical practice.”

For further reading on this research, please see the Biophotonics Imaging Laboratory website and the related NIH/NIBIB Center website for the Center for Label-free Imaging and Multiscale Biophotonics (CLIMB) website.

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ABOUT HIPO

Established in 2020, NCSA’s Healthcare Innovation Program Office (HIPO) enables healthcare partnerships that leverage NCSA’s dedicated technology and expertise in areas such as HPC, software development, visualization, data analytics, AI, and information security.  HIPO guides industry clients and academic researchers to solutions and expertise that meet their computing needs.  The people of HIPO are proud partners and stewards of NCSA’s resources, poised to assist users on their journey with NCSA.