spatial biology

Chris Mason, Professor of Physiology and Biophysics and prolific genomics researcher at Weill Cornell Medicine, joins us to talk about what he’s doing with the new generation of spatial biology tools.

The first papers we dive into are his work on COVID. Chris says the spatial tools have shown us the ravages of the coronavirus on the body like nothing we’ve seen before, i.e. the tissue damage from the cytokine storms and “the long term perturbations such as seeing cells far apart that were usually hanging out together.”

Does this new resolution open up all kinds of questions for not just the SARS-CoV-2 virus, but for other viruses Chris has long studied? And does he think the pandemic will spark an “age of virology” research?

Chris says he’s using the new spatial tools in his work with NASA as well as his grander metagenomics projects and believes the companies making these new tools are "just getting started."

Speaking of space, Chris has a new book out this summer into which he has poured much of his vast knowledge of genomics and science, his hope for our species, and a personal plea. It’s called, The Next 500 Years: Engineering Life to Reach New Worlds.  Go check it out.

And check out our sponsor links as well. Thanks to NanoString for underwriting this new series.

David Steffin is a cancer researcher and physician at Texas Children's whose particular focus is on pediatric cancers. He begins today’s program with some interesting numbers.

The international community has made a lot of progress in childhood cancers over the past few years. In the ‘60s and ‘70s, the survival rate of pediatric leukemias was 5-10%. Now it’s greater than 90%, and higher in some subtypes. It’s not as good in solid tumor types, but still much better than it was, around 60 to 70%. David is focused on the hardest to fight—those solid tumor cancers with survival rates below 30%.

To go where no researcher has gone before, David is turning to the latest tools for help. Today he shares with us the impact of new spatial biology technology on his work, offering a close look “under the hood.”

How are the new high-resolution images of spatial technology leading him to new biomarkers? What does the so-called mapping of this new technology tell him—how does it help to know the proximity of certain exhausted T cells, for example, to certain parts of the tumor?

It’s an exciting time for researchers using this new technology. How is the spatial community developing and sharing their data and working together in real-time?

Thanks to Akoya Biosciences for sponsoring David's show and our first series on spatial biology.  

One of the hottest new trends in biomedical research today is what is known as spatial biology--the ability to capture tissues in a 3D context. It was named Method of the Year by Nature Magazine in 2020.

And one of the first automated instruments launched in this market was the GeoMx Digital Spatial Profiler by NanoString. CEO Brad Gray is here to tell us the story of the birth of the DSP and the revolution of 3D biology. What will these new tools enable for the basic and translational researcher?

We’ve all heard of and perhaps worked with data from The Cancer Atlas Project. Now, with the help of new spatial biology tools, researchers at the Mayo Clinic are developing what they call The Cancer Immunome Project. This is a comprehensive effort to fully characterize the immune system and how it interacts with and fights off cancer.

Today we talk with J C Villasboas, a physician-scientist at Mayo who co-started the project. He’s also Director of Mayo’s Immune Monitoring Core Facility.

J C says the immune system is of such complexity that it took the new tools of spatial biology—tools able to measure multiple biomarkers in real-time -- to be able to tackle such a project.

“We layer on top of the multi-parametric data which gives the cell some kind of identity, the spatial data because context in immunology is everything. It’s like real state,” he says. “And then we try to make sense of the spatial biology itself. And you can’t achieve that level of detail with a single or even two or three biomarkers. You have to have a technology which provides not only the depth but also the breadth of the immune system’s complexity.”

This raises some questions. Will the data from the project be widely available for the community? Are there efforts underway to standardize the data as there have been in the past with single marker platforms? And that all-important question, what is the path to the clinic for the new multiplexed assays?

As a practicing oncologist, J C is excited about the answer to this last question and the unmet clinical needs that will be satisfied: much faster turnaround, less tissue needed, and the ability to work at tough marginal areas.

First it was all about biomarkers. Then panels of biomarkers. But biology is complicated. Why does one patient respond to an immuno therapy when another which shares the same biomarker does not?

Welcome to the age of spatial biology.

Garry Nolan joins us today. He's a professor in the Department of Pathology at Stanford who's career has been a journey of seeing intracellular happenings more and more in context. Check out this cool analogy from a new paper his lab put out in Cell.

"The tumor micro environment (TME) is like a city composed of neighborhoods (e.g., industrial, residential, or agricultural), which are regions where specific functions of the city occur. These neighborhoods are distinguished by their composition of buildings, activities, and people, but they exhibit behavior of their own, such as industrial output or energy consumption. At a more granular level, people (e.g., teachers, doctors, and construction workers) play integral roles in the city’s function. The same concept applies when studying tissue.”

Today Garry walks us through the transition over the years from biomarker to spatial biology. He then discusses the Cell paper demonstrating that for the first time his lab is seeing that some "neighborhoods" react differently than others in the tumor micro environment. What will this mean in the clinic for patient treatment?

The technology making this possible is the CODEX platform, one of several developed in Garry's lab over the years. He tells of its conception and anticipates how it might evolve in the future.

The history of biomedicine goes something like this:

1. A new tool is invented. 2. New tool is used in research labs to generate new data and new hypotheses. There is new science. 3. New tool is used in clinical setting to confirm this new science with real patients. 4. Then new tool is adopted into clinical use.

All the buzz these days, single cell DNA analysis instruments have just made it into step three.

Today we talk with Koichi Takahashi, Assistant Professor in the Department of Leukemia at MD Anderson and author of the largest clinical study to date using single cell analysis in the study of AML.

For years physicians and researchers have been testing patients for well known cancer driver mutations such as KRAS and BRAF with next generation sequencing tools, or what are now being called “bulk sequencers.” Koichi points out today that new single cell analysis tools are allowing researchers to see the unique genomic environment that lead to the common driver mutations and may be responsible for why each patient responds differently to the same therapies. Knowing each patient's individual tumor genomic environment--and not just the final driver mutation such as KRAS-could lead to effective tailored treatment.

“The development of cancer cells is like Darwinian evolution. They are adapting to the selective pressure of the tissue ecosystem. And by looking at the single cell clonal architecture of the mutations, we can actually build a phylogeny tree of how a particular patient's leukemia developed—like even before they were diagnosed with leukemia. Over the years how this leukemia was created—this single cell DNA sequencing can inform us of this history.”

Is this new scientific understanding able to impact yet how Koichi is treating his patients? What is next for this technology and for the field of AML research and treatment?