Plenge Lab
Date posted: January 25, 2015 | Author: | No Comments »

Categories: Drug Discovery Human Genetics Precision Medicine

Dear Mr. President,

I was very pleased to listen to your State of the Union address and learn of your interest in Precision Medicine. As I am sure you know, this has led to a number of commentaries about what this term actually means (here, here, here). I would like to provide yet another perspective, this time from someone who has practiced clinical medicine, led academic research teams and currently works in the pharmaceutical industry.

Let me start by acknowledging that I know very little about your plan, but that is because no plan has been announced. However, that inconvenient fact should not prevent me from forming a very strong opinion about what you should do. Similar behavior is observed in politics (which you know well) and sports radio (see for example “Deflate-gate”). So here it goes…

I want to clarify my definition of “precision medicine” (see here for my previous blog on how this is different from “personalized medicine”). In the simplest of terms, precision medicine refers to the ability to classify individuals into subpopulations based on a deep understanding of disease biology. Note that this is different than what clinicians normally practice, which is to classify patients based on signs and symptoms (which can be measured by clinicians as part of routine clinical appointments).…

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Date posted: January 19, 2015 | Author: | No Comments »

Categories: Human Genetics

Recently I was asked by the American Society of Human Genetics (ASHG) to provide my perspective on career and professional development in genetics (see here). At about the same time, I read the book “How Google Works”, by Google Executive Chairman and ex-CEO Eric Schmidt and former SVP of Products Jonathan Rosenberg. A very creative slide deck accompanies the book, which is definitely worth a few minutes of your time (here).

Both got me thinking about opportunities in the pharmaceutical industry for genetic graduate students. Here are a few thoughts based on the outline from the Google slide deck.

What is different now?

In human genetics, large-scale genotyping and sequencing is unlocking the inherited basis of most complex and rare traits in the ideal model organism, humans. This is very different than it was just a few years ago. But there is more: this is happening at a scale that will not likely stop until most humans on the planet have their genome sequenced. Like the “Internet of things”, there will soon be a “Genomes of things”, in which our genomes will be connected to all sorts of data – electronic health records, wearable technology, portable blood monitoring, etc.…

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Date posted: January 16, 2015 | Author: | No Comments »

Categories: Drug Discovery Human Genetics

Welcome to our first blog of 2015 on genetics/genomics for drug discovery. After a nice vacation in sunny Arizona flying drones (here), I am back soliciting ideas from our Merck Genetic & Pharmacogenomics (GpGx) team. This week’s pick riffs off the events at J.P.Morgan 2015, where there were a number of interesting deals made by pharmaceutical companies and genetic companies (see here, here, here).

With all of this interest in human genetics, it raises the question about how genetics can be used to develop new drugs. The first step is to go from “genes to screens”. That is, the first step is to progress from a human genetic variant associated with a clinical trait of interest to an actual drug screen. This week’s article, published in Nature Chemical Biology, describes one example (see here, here).

Summary of the manuscript: Deleterious mutations in the ABHD12 gene cause a rare neuroinflammatory-neurodegenerative disorder named polyneuropathy, hearing loss, ataxia, retinitis pigmentosa and cataract (PHARC, see here). A similar phenotype is observed in ABHD12-deficient mice. ABHD12 is an enzyme degrading lysophosphatidylserine (lyso-PS), a signaling lipid known to regulate macrophage activation. The Nature Chemical Biology study by Kamat and colleagues describes the chemical proteomic identification of a related enzyme, ABHD16A, which synthesizes the terminal step leading to lyso-PS generation.…

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Date posted: January 4, 2015 | Author: | No Comments »

Categories: Drug Discovery Human Genetics

I got a drone for Christmas. The first thing my wife asked me was, “Why do you need a drone?” I did not have a great answer, other than to say it would be fun to take aerial videos. My sister teased me, as did my kids, nieces and nephew (Sam Sutherland). They said I was obsessed; they said I was acting like a little kid. My neighbors were worried – “no more nude sunbathing” was awkwardly expressed by more than one.

The new recreational drones represent pretty cool technology. Just a few years ago, the technology was not available to stabilize and control the flying of drones…at least not at an affordable cost. Now, GPS satellites and gyro sensors can do just that. Until recently, the range on remote controlled drones was relatively limited. Now, wireless communication allows for first-person viewing and long-distance control at long-range (up to 500 meters from my Phantom DJI FC40 drone). And until recently, the cameras attached to drones were not of sufficient quality to record high-definition images. Now, simple microchips installed in HD cameras with stabilizing functions allow for professional-grade photography (e.g., GoPro).

And with these drones, there is a new perspective on old things.…

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