Dec 152016

In the Dec 15, 2016 issue of Cell, three papers from Jonathan Weissman, Aviv Regev, and Ido Amit described this really cool technique called Perturb-seq. This is a technique to do focused CRISPRi screen (of ~100 sgRNAs) followed by Drop-seq. Basically they use CRISPRi to knockdown different genes in different cells, then examine the transcriptome outcome of the different knockdowns through single-cell RNA-seq. Very often after a genome-wide CRISPR screen, you often have many hits, so they can use CRISPRi to validate each hits and explore the mechanism of the KD effect. Although single-cell readout from Drop-Seq could be noisy, they sequence ~500 cells per CRISPRi, so the average from the ~500 should give a much more robust expression readout. Perturb-seq doesn’t have to be a validation step of a CRISPR screen, as I would be totally excited to see the transriptome in MCF7 after knocking down 100 different transcription factors, chromatin regulators, and kinases, as Aviv’s paper beautifully demonstrated. This is super cool!! For a long time we have been searching for a proper application for single-cell RNA-seq in translational cancer research. Perturb-seq really sold me on the practical value of Drop-seq.

Now, before we get too excited, we should examine the raw data from Perturb-seq. Seeing is believing! If the data quality is indeed excellent, then there will be opportunities to develop computational methods for the systematic modeling of gene regulatory networks. Aviv’s paper has some cool informatics modeling, but I am sure there are still good opportunities!!

I got an email the morning after I posted this blog, from my Stanford labmate Serge Saxonov. Turns out he is the CEO of 10X Genomics, the technology platform that enabled the Drop-seq part of Perturb-seq. What a happy surprise it is! I haven’t see Serge since I graduated. He started 23&me right after PhD, and now is the CEO of 10X Genomics, wow!!

Dec 082016

When I was traveling this fall, I watched the movie Me Before You over two flights. A dashing rich young Will Traynor became paralyzed from a car accident. Despite his family members and caregivers trying to cheer him up, he didn’t see his condition improving so asked his family to end his life (sorry for the spoiler). The ending was a surprise, which really got me thinking. Recently I also had a good discussion about it with my girlfriends. They thought Will was good and real, but I didn’t think very highly of him. His brain was still very sharp, and he had good connections to make a difference in the world. If he wasn’t so rich, had a wife and kids to support, could he afford to die?

Today at the San Antonio Breast Cancer Symposium, Eric Winer gave the William L. McGuire Memorial Lecture. He discussed the recent development and challenges of breast cancer treatment. At the end he talked about his own history. He was born with hemophilia and frequented hospitals as a child, at a time when the life expectancy of hemophilia patients was 20. When he was 13, Factor VIII became available which with injections every 5 days, he could be symptom free. This motivated him to be a doctor. Since Factor VIII was isolated from blood donors, he got HIV infection in 1989 and was kicked out by his dentist. With the development of HAART, a cocktail taken daily for HIV patients, he can live with HIV. Then it turns on HIV infection from blood donors also often accompanies hepatitis C, so he had to take 2 more years of interferon and ribaviron to treat hepatitis C. In 2003, he got GI vascular shunt from the HIV treatment and liver necrosis, which he had to take a surgery to bypass. Despite these harrowing experiences, he now has a lovely family with 3 successful kids, and appears as healthy and energetic as ever. He thanked biomedical research, also the US healthcare system for giving him access to newest drugs to treat his conditions. So the hope for cancer patients, at least in US, is also that with advances in biomedical research, cancer treatment will advance significantly in the coming years.

It was such a moving and motivational talk! Before I only knew Eric as the preeminent breast cancer oncologist, the head of our breast cancer SPORE, who always appears happy and confident. I didn’t know he had to live through so much, and even now has to regularly take the Factor VIII injection and HAART medication. He has all the excuses in the world to complain about his fate, and yet he has the optimism and grit to achieve so much in life. Actually looking around, many of my very successful relatives and colleagues have had personal or family tragedies, divorce, illness, or death (of loved ones), etc. And yet they had the optimism and grit to pull themselves together and try their best. Eric mentioned that growing up with hemophilia shaped him, so he was able to deal with later challenges in life. Compared to them, I feel so lucky and want to give my best to my work and the world.

So now I am even more convinced that Will should not commit suicide. Christopher Reeve didn’t commit suicide, instead he made his last 9 years of paralyzed life worthwhile and did so much good to the world. Even though Will’s illness was not curable at the time, there is always hope that a cure will be found with new biomedical research and development.

Dec 012016

Just finished NIKE founder Phil Knight’s book Shoe Dog. An absolute must read, not only for its content, but also for its humor! The true stories about real people are infinitely more fascinating than novels, you see the laughs and the tears in their experiences.

When I read books about Steve Jobs, Jeff Bezos, and Elon Musk, I felt that these people are geniuses way beyond my league. They knew exactly where they want and are going from the start. But Phil Knight is more like us mortals, improvising as he went along, and just trying his best. His advice was quite intriguing: “Let everyone else call your idea crazy, just keep going. Don’t stop, don’t even think about stopping until you get there, and don’t give much thought towards where there is.” Indeed, in work, I wish we plan strategically and do the right things towards the goals, but very often we end up in a different place from where we thought there is.

NIKE was able to keep most of its founding team for many years, especially those who love sports or running. It boosted my respect for runners who have that grit and optimism. I bought new NIKE free running shoes. Time to get back to regular exercise!