Quantitative Pathology with David Rimm, Yale

David Rimm, Professor of Pathology at Yale, was doing spatial biology since before it was called that. He’s known for counting. And he’s been going beyond—beneath?--the model of the cell in biology for years.

Here’s how he explains it in today’s show. Precision medicine, ironically, is a world of black and white. Biomarkers are either present or not present. But David wants to know how much of the biomarker is present because that matters when giving a therapy. It’s that step that makes the new spatial biology tools very cool for him to work with, and that step that takes biology to the next level—and perhaps medicine over the next five or ten years.

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.

Why Internet Traffic Directors Should Sit Down with Biologists: George Poste Talks Complex Systems


George Poste, Chief Scientist, Complex Adaptive Systems; Regents’ Professor and Del E. Webb Chair in Health Innovation, ASU
Bio and Contact Info

Listen (5:51) A paradigm shift to systems thinking

Listen (4:28) Note to those setting curriculums

Listen (4:37) How do we bring the clinical and research worlds closer together?

Listen (8:53) Simulating complex adaptive systems

Listen (2:46) Science only one of the challenges

Listen (5:13) Why the disparity in reimbursement rates for Rx and Dx?

Listen (7:51) Something special happening at ASU

If you’ve ever heard a talk by today’s guest, George Poste, you’ve no doubt come away scratching your head, overwhelmed by the complexity of human biology. As if the science challenges don’t give one enough of a headache, George continues his carpet bombing approach with all that is wrong with our healthcare ecosystem as well.

Back in the '90s at SmithKline Beecham, George realized that the field was way overly reductionist and that we must do more to look at human biology as a system. He made his way to ASU where he then launched the Complex Adaptive Systems Initiative to bring together biologists, engineers, data scientists, and others.

What is a complex adaptive system and how can simulating it help us decipher human biology?

"A complex adaptive system,” George answers, “is one in which the collective behavior of the component parts cannot be predicted by an analysis of one or more of the these component parts.”

Whether you’re looking at global climate or intracellular wiring, George says it’s all about information transfer in a "network architecture."

The architecture of George’s way of speaking is also complex. With frequent use of the “dash”, George mimics in his own sentence structure the systems he’s describing. His syntax tends to bloom like a natural organism.

An example:

“The question now, then, is how can--by understanding the molecular pathways and coupling of those pathways—because we all tend to think in linear terms (you see the diagrams of a molecular pathway tend to be a series of straight arrows, but in fact what it is is a series of pathways that are interlinked)—because the one other feature of complex adaptive systems is that they have enormous redundancy built into them, so that if one bit goes down --you know it’s the classical model of the internet—if you take out a series of nodes, there are whole ways of distributing traffic around that . . . if you extrapolate that to cancer therapy, yes, you may knock out a particular node with your targeted therapy, but what you need to know now is what are the most likely network couplings of that particular pathway for the compensatory redundancy pathways which will kick in that will confer resistance on a cancer cell.”

Did you get all that? The internet is an interesting comparison. So if we bring together some of those engineers who work on routing internet traffic with some biologists they should be able to have a good time, right?

"Absolutely," George says.

As we conclude the interview, he acknowledges that there is something special going on at ASU, a new paradigm and openness to inter-disciplinary work that is unique. How is it fostered and funded? And what can we expect from this approach?

Fasten your seat belts and hold on for the ride. Suspend your need for short, easy sentences, and rewards await. Presenting systems thinker, George Poste.

Podcast brought to you by: National Biomarker Development Alliance - Collaboratively creating standards for end-to-end systems-based biomarker development—to advance precision medicine

Raising the Standards of Biomarker Development - A New Series

We talk a lot on this show about the potential of personalized medicine. Never before have we learned at such breakneck speed just how our bodies function. The pace of biological research staggers the mind and hints at a time when we will “crack the code” of the system that is homo sapiens, going from picking the low hanging fruit to a more rational approach. The high tech world has put at the fingertips of biologists just the tools to do it. There is plenty of compute, plenty of storage available to untangle, or decipher the human body. Yet still, we talk of potential.

It's All About the Patients: Mara Aspinall, CEO, Ventana

Podcast Sponsor: BioconferenceLive- Register for free to the upcoming Spring Conference on Laboratory Animal Science, February 15-16


Mara Aspinall, CEO, Ventana Bio and Contact Info

Listen (4:37) How's Tucson?

Listen (3:36) Mission at Ventana entirely devoted to cancer

Listen (2:21) Digital pathology

Listen (2:29) What has made you a successful CEO?

Listen (1:15) It's all about the patients

Listen (1:21) A business person leading scientists

Listen (1:35) What inspires you about Roche?

Listen (3:49) Challenge of being a new CEO

Listen (1:26) Industry's failure with cancer

Listen (8:24) Leadership style

Listen (3:58) Challenge for personalized medicine

Listen (4:47) An early voice for personalized medicine

Listen (2:10) Personal motivation

An early pioneer of personalized medicine, Mara Aspinall joins us today. In August she was appointed the new President and CEO of Ventana Medical Systems, and global head of Roche Tissue Diagnostics. Ventana is known for their leading edge instruments and assays which support diagnosis and inform treatment decisions of cancer. Mara is formerly from On-Q-ty where she was founder and CEO. On-Q-ty is a diagnostics start-up focused on using biomarkers in circulating tumor cells to help in the prevention and treatment of cancer. She began her career in diagnostics as president of Genzyme Genetics. Mara has been a strong voice for Personalized Medicine, has sat on the board of the PMC and was a founder of Epimed, the European Personalized Med Coalition. She speaks regularly about the challenges and opportunities in this field. Mara joined us for our first show here at mendelspod, and we are happy to have her back. (Recorded 10/2012)

Breathing Life into Complex Data: Doug Bassett, Ingenuity

Podcast Sponsor: Appistry- Delivering the most cost-effective and the highest quality analytics for your NGS data. Jumpstart your analysis with runs beginning at just $99. Appistry, complex analytics made simple.


Doug Bassett, CSO & CTO, Ingenuity Systems Bio and Contact Info

Listen (2:28) Breathing life into complex data

Listen (1:14) Where exactly is the bottleneck?

Listen (4:56) New products

Listen (4:33) Curating the Knowledge Base for 14 years

Listen (5:10) Working with clinical customers

Listen (3:17) Why come to Ingenuity?

Listen (6:12) Are arrays dead?

Listen (:48) Is there a preferred sequencing platform?

Listen (2:01) Personal path to Ingenuity

Listen (1:31) Looking ahead

Today we’re coming to you from Redwood City, CA at the office of Ingenuity Systems. Founded in 1998 by Stanford graduate students, Ingenuity Systems is taking on the challenge of next-generation knowledge management for the life sciences community. Today, Ingenuity's products are used by thousands of researchers at hundreds of leading pharmaceutical, biotechnology, and academic research institutions worldwide. Joining us to talk about the company and what they do is the CSO and CTO, Doug Bassett.

Personalized Medicine: Histone biomarkers with PrognosDX

Podcast Sponsor:


Kamran Tahamtanzadeh, CEO, PrognosDX, Bio and Contact Info

Macro environment very important Listen (8:13) Macro environment very important

<img src="/images/speaker.jpg" alt="Not just about a few markers/> Listen (2:27) Not just about a few markers

What does the service tell a doctor? Listen (5:25) What does the service tell a doctor?

Histones studied only recently? Listen (7:56) Histones studied only recently?

From scientist to businessman Listen (3:25) From scientist to businessman

Poet and painter Listen (2:03) Poet and painter

Histone like a soccer ball Listen (3:44) Histone like a soccer ball

Today we bring you the story of a company which is moving us closer to the promise of personalized medicine. Joining me is Kamran Tahamtanzadeh. He’s the founder and CEO of PrognosDX, a new company in Palo Alto, CA aiming to improve the treatment of cancer through epigenetic technology, specifically with histone biomarkers. Kamran was formerly with Ventana Medical Systems (now Roche) and MetriGenix.

Proteomics with Caprion's Martin LeBlanc

Podcast Sponsor: Biotix, Inc. - Free Samples


Martin LeBlanc, CEO, Caprion, Bio and Contact Info

Proteomics overshadowed by DNA sequencing? Listen (1:07) Proteomics overshadowed by DNA sequencing?

Caprion and CellCarta Listen (7:17) Caprion and CellCarta

Novel drug targets and biomarker candidates Listen (4:34) Novel drug targets and biomarker candidates

Promise of proteomics and protein diagnostics Listen (3:10) Promise of proteomics and protein diagnostics

Proteomics and genomics Listen (7:11) Proteomics and genomics

A Human Proteome Project? Listen (2:57) A Human Proteome Project?

Proteomics outlook Listen (4:49) Proteomics outlook

As part of a series on Personalized Medicine, today we explore a leading company in the field of protein biomarker discovery, Caprion Proteomics. Caprion’s proprietary technology, CellCarta, enables comprehensive measurement of protein expression differences across large sets of biological samples. They have been providing protein biomarker and target identification services to over 30 major pharma industry clients in all of the major disease areas. Here to talk to us about the field of proteomics and his company is the CEO of Caprion, Martin Leblanc.