The expertise and information to solve almost any cancer problem — even the most difficult ones, like pancreatic cancer — exist at Johns Hopkins.

JAFFEE

Elizabeth Jaffee, M.D., Kimmel Cancer Center Deputy Director and the Dana and Albert “Cubby” Broccoli Professor of Oncology, one of the world’s foremost pancreatic cancer experts, is leading research and patient care in a new direction.

Jaffee created a Convergence Institute, where doctors, nurses, astronomers, engineers, computer scientists, physicists, bioethicists, biologists, materials scientists, mathematicians and other experts from a variety of fields work side by side to amass and apply their knowledge to cancer.

Beginning with pancreatic cancer, they are solving complicated and vexing problems, building new technologies and considering out-of-the-box, creative new approaches that can only be found through this type of directed collaboration. Together, they are planning and charting new cancer prevention, detection and treatment strategies that intricately apply every bit of knowledge available.

LAHERU

It represents a new tactic, different from the assembly line approach that, although useful, applies consecutive contribution of expertise, implementing one thing at a time and offering separate and distinct components of the whole. Instead, it brings a convergence of expertise — people coming together in synergy to merge their ideas and knowledge into a new whole.

Imagine, for example, Madame Curie, Katherine Johnson, Albert Einstein, Frederick Douglass, Steve Jobs, Leonardo da Vinci, Aristotle, Stephen Hawking and Sally Ride working together, combining their ideas and expertise to solve a problem. This is what Jaffee envisions for cancer.

FERTIG

Amassing Talent

Jaffee recognized the immense talent amassed at Johns Hopkins and had the vision to bring it all together to combat cancer, which is among the most complex diseases. While each new discovery advanced the understanding and treatment of the disease, it tended to also reveal new ways the cancer cell corrupted and disarmed natural biological processes that threaten its ability to survive, grow and spread.

“Cancer is a complicated problem, and to solve this problem, we need more than cancer biologists and cancer doctors,” she says.

The answers, she says, lie in the data we are accumulating, but it requires physicists, engineers, computer scientists and others to turn it into meaningful information that can be used against cancer. Real progress will be measured by who is best able to interpret and use these massive amounts of data to help patients.

“Convergence is the only way to assemble the expertise to make use of all of the tools available and to tailor them to cancer discovery and medicine,” Jaffee says. “It will allow us to convert data chaos into data order.”

All Hands on Deck

Daniel Laheru, M.D., co-director of the Skip Viragh Center for Pancreas Cancer Clinical Research and Patient Care, says the Convergence Institute has an all-hands-on-deck philosophy. It is physically located on the seventh floor of the Skip Viragh Outpatient Cancer Building, but in practice, it extends to every specialty — 34 departments from five Johns Hopkins University Schools — and includes experts who do not typically have a seat at the table in the world of medicine.

“Engineers, physicists and other scientists we don’t typically work with, come at a problem from a different perspective. They find clues we don’t see,” says Laheru. For cancer clinicians and scientists who pioneered the multispecialty approach of bringing together all the medical specialists involved in treating pancreatic cancer to develop a treatment plan, expanding this approach to include experts from other scientific areas makes sense.

They begin with development workshops. A cancer doctor like Laheru explains the problem to this expansive and diverse group of experts who make up the Convergence Institute. After, there is a thorough, often hours-long discussion of the problems.

“We speak a different technical language in medicine than an engineer or physicist, so we have to make sure we have a common understanding of the problem,” says Jaffee. “Then, working together, we bring our different tools to the problem.”

Teams form to develop and study different ideas and approaches, and determine which one or ones work best and merit further investigation.

Jaffee wants to make sure they share information rapidly. She says their colleagues from other fields don’t wait a year for a publication to get the word out on their research, as is often the case in medicine. Instead, they put it out on websites right away so they can share their computation methods and get insights from other experts.

Convergence Institute experts have already begun designing their first studies.

“We’re really the only ones doing it clinically,” says Laheru. “We’re ahead of the curve.” 

From Math to Medicine

“Every problem — even cancer — can be informed by math,” says Elana Fertig, Ph.D., mathematician and computational biologist and co-director of the Convergence Institute. The Convergence Institute is helping her make the math-to-medicine connection.

Fertig, who began her career as a weather forecaster, made the career change to cancer researcher because of cancer’s complexity. In predicting weather, Fertig says the challenges were taking different sources of data and integrating them with computer models to improve forecasts.

Now, she is applying the same strategy to cancer, gathering data, developing computer models to analyze it to predict how a cancer will behave and how it will respond to different types of treatments.

Fertig developed artificial intelligence methods that decipher the complex circuitry and interconnectivity of gene activity that controls cell growth, death and other behaviors in tissue and organ development, and relate this gene activity to what occurs in other tissues and across different species.

“We are bridging experimental models and divides by building a community of people who are cross-disciplinary to engage with the Cancer Center,” says Fertig. “We’re getting at things we haven’t gotten at before and looking at them in a new way, taking principles from other fields to figure out how to overcome failures in treatment.”

Most laboratories start with a pipette to do an experiment. Fertig and collaborators start with data.

“We go in the reverse direction. We start with the data that has already been generated, and then we go to the lab to see what we can learn about them,” she says. “Cancer is a puzzle, and we piece it together using different technologies and different areas of expertise that will get us the answers.”

The Tools of Convergence

TAUBE

The Google Maps of cancer: New computational approaches are providing a never before seen view — at the single cell level — of the tumor and all of the cells in and around it that contribute to its survival. Similar to Google Maps, the fine details these new technologies provide offer a detailed view of how and where the tumor exists in the body and how it interacts with surrounding tissues. It’s possible to zoom in on spatial features and also pull back to get a fuller view. Pathologist Bob Anders, M.D., Ph.D., can do the same thing at the cellular level to provide a “Google Map” of an organ and surrounding tissue and organs. Provided with any list of proteins, Anders can quantify their abundance, where they are in the tumor and how they are affecting the growth and spread of a cancer.

SZALAY

From Astronomy to Cancer: The images of the night sky that astronomer and computational scientist Alexander Szalay’s datasets created are remarkably similar to the terrain of the cancer cell and its environment. Szalay and his Kimmel Cancer Center collaborator Janis Taube, M.D., M.Sc., developed AstroPath, a comprehensive platform for high-quality imaging and mapping of microscopic sections of tumors. Taube and Szalay are co-directors of the Mark Foundation Center for Advanced Genomics and Imaging.

These deep-learning algorithms, derived from artificial intelligence, provide sophisticated models that help predict what treatment is the best option for a patient. Jaffee and other cancer experts can use their technology to determine how likely a cancer is to respond to different types of immunotherapy or other treatments.

Single cell sequencing: Luciane Kagohara, Ph.D., uses a specialized technology called single cell sequencing, which offers a detailed view of the tumor composition and enables scientists to measure all cell types in the tumor and examine their function. With the rapid advances in the field, it’s now possible to zoom in on spatial features and identify how those same cells interact with one another without dismantling the tumor samples. This approach can help scientists and clinicians discriminate between treatment resistance built into the tumor and resistance that is acquired during treatment.

KAGOHARA

Organoids: Small, natural replicas of human tissue, called organoids, are another example of a new technology used in the Convergence Institute. Richard Burkhart, M.D., and pathologist Laura Wood, M.D., Ph.D., are using pancreas organoids, ultra-tiny replicas of a patient’s pancreas, grown from their own cells, to better understand the mechanisms of how a cancer originates and grows, and as a unique way to test responses to treatments. Wood and Burkhart think the organoids reflect the tendencies of the actual patient tumor. For example, if an organoid grows more quickly, it could be a warning sign that the tumor may be more aggressive and dangerous.

A New Era

Jaffee believes the Convergence Institute brings the people together and provides the tools needed to fully understand every cancer. As a pancreatic cancer expert, she believes it represents a new era of cancer research.

“I’ve been researching pancreas cancer for 25 years, and I am very optimistic that we are on the verge of turning this very deadly disease into at least a chronic disease patients can live with,” says Jaffee. “It gives me goose bumps knowing that the work we’re doing in the Convergence Institute and all that we’ve learned will save lives.”