Aug 252012

I was looking at DMS Bulletin introducing new faculty at HMS last night, and saw that many new faculty gave excellent advices to graduate students. This prompted me to search for “advice to graduate students” on Google (interestingly “advices for graduate students” gives some different hits). Wow, what a treasure trove of wisdom. Here are a few excellent examples:

I wish someone had told me these when I started graduate school 15 years ago, and I wish I had shown our first graduate students at Tongji 3 years ago. Every graduate student should read it when they enter graduate school, and read it again when they have problems during graduate school. It is very interesting to see that some of the advices have been incorporated into our core values, and I should read me to see whether our core values could be improved.

This experience reminded me that we are in such an amazing information age. Any time I have a question, I can find good answers online. I spent several afternoons during the summer to teach Tongji students how to write CVs and papers, scientific marketing, etc. Probably better, I should teach them how to find answers online and learn themselves, which could help them career success after graduate school. I should also better use the web to teach myself.

So try it out, do some exploration such as:

How to respond to reviewers’ comments
Time management advices
How to select thesis project
Interacting with graduate advisor
How to read a biological paper
Work life balance tips
How to prepare a scientific talk

Have fun!

Aug 182012

On 7/30/2012, we had a senior lab member retreat for our Tongji lab. It was a very fruitful meeting, where senior members make plans for the following year, which includes grants to apply, new papers to submit, major research directions and projects, new student training, wet lab establishment, fall lab activities, and logistical issues about lab management.

In addition, we established the lab Core Values. Initially inspired by Zappos, Yong and I have been thinking of establishing the lab Core Values for a while. After some active discussions with the senior members, we came up with the following five points:

  1. Conduct world class research
  2. Make a solid contribution to the community
  3. Motivate scientific curiosity and discovery
  4. Train talents with integrity, initiative, perseverance, and optimism
  5. Build a collaborative and synergistic environment

Actually these probably fit well with my DFCI lab as well, and we will continue to use this as guidance for many of the activities in the lab. I should spend sometime to come up with my personal core values as well.

Jul 262012

In a recent NIH study section trip, Xihong told me that it is important to belong to a community. I have picked computational cancer epigenetics as my future research direction, which is naturally interdisciplinary. As a result, I don’t quite belong to any of the following communities (characterized by the conference they go to): statistics (JSM), bioinformatics (ISMB), genomics (Biology of Genome), chromatin (CSHL, Gordon, or Keystone conferences on chromatin and epigenetics), or cancer (AACR). Most of my closest colleagues to go the Cold Spring Harbor Systems Biology of Gene Regulation, which include people who use genomics and bioinformatics approaches to study transcriptional and epigenetic gene regulation. However, I follow their work closely, so sometimes don’t learn as much from this meeting any more.

Over the years, I have grown to enjoy the domain biology meetings such as cancer or chromatin meetings much more than the genomics and bioinformatics meetings. In the future, I should alternate between the CSHL Systems Biology and Biology of Genome meetings, then go to one cancer (AACR) and one epigenetics (keystone or CSHL) meeting every year. Recently there are also some good cancer epigenetics meetings, which could be very interesting.

Jul 152012

Wei Li stopped by Shanghai to attend the Tongji summer camp (for graduate student recruitment). He told me that Gongming Pu said that nowadays the way to publish a Cell, Nature, and Science (CNS) paper is to use new technologies to re-investigate decade-old problems that are published in CNS, and it is especially exciting when the new technology gives different results as previously reported in those CNS papers.

This is quite an interesting idea. I only determined to focus my research on cancer last spring, so don’t quite know the general landscape of the cancer field, nor understand what the big and important cancer problems are. I started searching for original research papers related to cancer that are published in Nature, Science, Cell, and Cancer Cell, and only found ~1800 hits since 1990. Even if I include JAMA and New England Journal, the total hit is less than 4000. If I read the abstracts, and occasional the full paper, of 20 papers a day four days a week, I could finish all in a year. I will do it with members of the lab in the coming year.

Jul 132012

In 2011, we spent some efforts looking at integrating ChIP-seq with GWAS data. That led me to the realization that for cancer studies, it is much more fruitful to study somatic mutations than germline mutations, and studying normal populations are less likely to be cost-effective.

Ever since we sequenced the LNCaP / abl and MCF7 / LTED genomes, I have been thinking of establishing our whole genome sequence analysis capacity in Tongji University, China. Our assistant professor Jianxing Feng got his CS PhD from Tsinghua University specializing in algorithms, so we thought that he would like the computational challenge. We held a focused journal club reviewing the high impact computational and biological papers for genome sequencing. To our surprise and disappointment, most of the existing algorithms are just brute force intuitive software with little algorithmic or statistic component.

Going to IBW, I realized that we are late in the whole genome or exome sequencing game. Many computational groups domestic and overseas are already analyzing massive amount of genome/exome sequencing data. The trend is clear, the first group can publish a good paper with only one whole genome; the second group will need to sequence 2 genomes; then future groups need to sequence 5 (pairs of) genomes, 10, 50, 100, etc to publish a good paper. The bar will rise just like for GWAS studies: the community would expect the sequencing studies to understand the function and consequences of these mutations. That’s where we have some expertise and should be prepared to make an impact.

Recent exome sequencing and whole genome sequencing comparing cancer normal or primary metastatic cancer genomes have yielded many exciting findings. The easy cases to investigate functional mutations are genes with copy number gain or loss, and most of these genes are clear oncogenes or tumor suppressors likely already identified before with CGH or SNP arrays. The functional consequences of these genes are easy to investigate with knockdown / knockout or over expression assays. Our current approach of combining RNA-seq with DNase-seq to profile the wild type vs knockdown / overexpression conditions is a good screening approach to generate initial hypothesis.

One area that is likely to create new research opportunities is long noncoding RNA (lncRNA). Theoretically CGH and SNP studies should have information on their copy number changes, except that previously people didn’t realize that they were genes. In addition to using RNA-seq and DNase-seq to investigate their function, one informative experiment might be to use oligo probes to specifically pull down the lncRNA and mass spec to study the proteins that interact with it. John Rinn seems to have some expertise in this area, and we should also explore this technique.

If enough tumors have been sequenced, and still people only observe point mutations but not copy number variations, it would indicate the mutation is not having weaker or stronger regulation of existing network of genes. The reason is that tumors could increase or decrease copy numbers to achieve similar goals of exerting stronger and weaker regulation. Instead, the mutation must be creating new links in the regulatory network. This type of gain of function mutations could be investigated by knocking in genes carrying the specific mutation, and examining its downstream consequences. This is not a trivial experiment, and we might need to think of more efficient ways to study these mutations.

May 062012

My husband recommended me to check out the Kahn Academy. The founder, Salman Kahn, a graduate of MIT and HBS, started tutoring his cousin and decided to put his videos online. He got overwhelmingly good feedback, and decided to quit his full time job as a hedge fund analyst to work full time on online education. For more information, check out wikipedia.

I checked out the website, and the content is quite amazing. They have over 3,100 short videos (usually 5-15 min) teaching contents from elementary math, to art history and finance. Kahn’s style is very interesting and leisurely. You can learn and also get entertained. I always admire people who can teach and make it fun. There are also very interesting and creative videos like the doodling math on spirals and Fibonacci number. I probably learned Fibonacci number a number of times in my life. But watching this video makes the content unforgettable for the rest of my life. Technology is changing the world and the way we learn!

Apr 152012

In a recent seminar trip to University of Michigan, I met with Bruce Richardson who explained the very interesting etiology of lupus, an autoimmune disease. He told me that lupus is caused by DNA demethylation, and substances that decrease DNA methylation could cause lupus as a side effect. Cancer drugs such as 5-aza with demethylation effect certainly have similar side effect, but cancer patients usually have bigger worries than DNA demethylation and lupus. He also explained why females are more likely to develop lupus, because an important autoimmune gene is on the X-chr. Females should have one X-chr silenced except in lupus patients, whereas males only have one copy of the gene to express.

Because of Bing Ren‘s talk on the association of aging with increased H3K27me3, I had always assumed that DNA methylation increases with aging. However, Bruce told me that in general DNA methylation decrease with aging, which could agree with Michael Zhang‘s idea that transposable elements are more active with aging. So perhaps the increased H3K27me3 with aging reflects the way cells compensate for the loss of DNA methylation. Since DNA methylation and H3K27me3 have their respective genome-wide specificities, maybe the specificity difference between the two could help explain the common aging-related disease.

Bruce also mentioned that antioxidant can reinforce DNA methylation, which partly explains why it is an anti-aging and anti-lupus agent. Also, from David Moore‘s research before, having a methylation-rich diet (plenty from vitamin tablet) could also prevent DNA demethylation, and perhaps aging as well.

Apr 072012

American Association of Cancer Research (AACR) has over 30K members, and the annual conference is one of the biggest scientific events in cancer. AACR 2012 attracted over 17K attendees, and is also the first AACR I attended. Because I brought my son to see Chicago and the Sears Tower, I missed many scientific talks and sessions. None the less, as my cancer 101 experience, it is still very interesting. There are three observations:

Computational cancer biology plays a surprisingly small role at AACR. Among the 17K attendees and thousands of abstract submissions, there were only 58 abstracts submitted to the computational biology track, which were presented in two poster sessions. Since the invention of microarrays, cancer biologists have been increasingly using genomic and other high throughput approaches, so computational biologists must be playing essential roles in their studies. Somehow they are not attracted to this meeting, or their importance has been underestimated. Being the chairperson of the track, I have to say that some of the abstracts we reviewed are just awful! There are many good computational biologists doing great work in cancer, such as Andrea Califano, Dana Pe’er, Peter Laird, Rafael Irizarry, Aviv Regev, Franzisca Michor, Yi Xing, Ting Wang, Josh Stuart, Jeff Chang, Gad Getz, and many more… I will try to help bring better computational biology to AACR in the future.

Epigenetics is still in its infancy. Many scientists and companies feel that they cannot miss out on epigenetics, but some don’t really know what questions they want to use epigenetics to answer, so actually don’t know the best way to conduct their epigenetics studies. Epigenetics is definitely important, but there is also hype. If used well, epigenetics can bring amazingly useful information to cancer studies. We should help bring good study design, experimental techniques, and analysis methods to the cancer field.

Asian scientists are under represented in the AACR leadership. There are numerous committees, awards, sessions and workshops, but very few chaired or even participated by Asian scientists. However, there are many excellent Asian cancer biologists doing outstanding work, but most just keep to themselves, and are not actively involved in the community. This is not just in science, but also clearly seen in industry and politics. Jewish really help each other and have a good sense of community, and this help them as a whole in every aspect. Nobody is born to take initiatives in the community, but we have to try, especially when we are young.

Coming to AACR, I realized how puny I am in the cancer field, but there are also good opportunities for me to make a good contribution. Now that I am determined to work on cancer, I should come back to AACR every year in the future. I also hope to bring better computational biology and epigenetics approaches, and more Asian scientists to the cancer community.

Mar 202012

After twice reading The Emperor of All Maladies: A Biography of Cancer last spring, I was determined to focus on cancer research in the future. Since then, I have been struggling to find the right cancer type to work on. Cancer is a deep field, and it takes a lot of efforts to become a real expert on any one cancer type. The ideal cancer for us to work on should satisfy the following criteria: 1) has high incidence and death rate in both US and China; 2) DF/HCC has demonstrated research excellence such as a SPORE program; 3) I am able to find good clinical collaborators in China.

Most of my previous collaborations especially with Myles Brown and Nelly Polyak have given us a footing in breast and prostate cancer research, although these two cancers (especially prostate cancer) are not as bad in China. DFCI is famous for leukemia and lymphoma research because of Sydney Farber and we have started collaborating with Jon Aster and Stephen Blacklow. We could also potentially collaborate with the Ruijin Hospital in Shanghai which has the best leukemia research in China and are also world renowned for their acute promyelocytic leukemia (APL) treatment. GI cancers, including gastric, liver, and colon cancers, are very serious in China. Epigenetic profiling and drug deliver for liver cancer is the easiest among all tumors, but DFCI is not known for liver cancer research. Lung cancer is probably the biggest cancer killer in both US and China. DFCI has an excellent lung cancer program and we could also collaborate with the Shanghai Pulmonary Hospital, although I previously had zero background in lung cancer research.

A couple of weeks ago, someone from Bill Kaelin’s laboratory at DFCI approached us for a collaboration. I started reading Kaelin’s website and papers. He has been amazingly productive with just a medium-sized lab. I know from my seminar visits that many of his former trainees are successful at various faculty positions, so he must be a very nice person and a supportive mentor. His pioneering work, such as that on E2F1, Rb, VHL, HIF, and EglN, has made quite an impact in cancer research. Interestingly, he is not focused on specific cancer types, but has been focused on tumor suppressors that function in multiple cancers, especially those that are related to cancer metabolism. This is a fairly new area for me, but both cancer metabolism and tumor suppressors are very exciting and promising. Maybe if we focus on cancer epigenetics, we don’t have to pick a specific cancer now, and could learn the different cancers on the way. Of course, it would take a lot of hard work and probably Kaelin’s genius (as told by his postdoc). At least I look forward to working with this group and learning a lot about cancer biology from them.