spatial biology


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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