spatial biology


Out of the Reductionist Trap: Brad Gray of NanoString 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?

Spatial Biology Enables The Cancer Immunome Project

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.

Mapping Intracellular Context: Garry Nolan on Spatial Biology

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.

Single Cell Analysis Shows Important New Detail in Key Clinical Study of AML: Koichi Takahashi, MD Anderson

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?



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