October 2019: Lu Lab

Background:

What is the main focus of your lab?

Our group is interested in understanding molecular mechanism of chromatin organization and genome access, as well as its implication for human developmental disorders and cancers.

How long have you had your lab? When did you join Columbia University?

We joined Columbia University in January 2018 so the lab is almost two years old!

How big is your lab currently?

We have a total of eight people of diverse educational background – two postdoctoral scientists, two graduate students, two research technicians and two Columbia College undergrads.

Where is your lab located?

We are located on the 3rd floor of ICRC building.

Current affairs:

What are the most exciting projects/directions in the lab at this moment?

One scientific direction that is quite exciting to us centers on exploring novel chromatin interactions. It is well-known that chromatin pathways such as DNA and histone modifications “crosstalk” to reinforce our genomes to be stably partitioned into distinct territories. Yet, only a handful of such interactions have been reported. We have been employing hypothesis-driven and system biology approaches to uncover new chromatin trans-regulatory mechanisms and determine how their dysregulation leads to human diseases. Eventually we hope that these efforts will lead to new targets that can be therapeutically exploited.

What are the biggest accomplishments that your lab recently had?

DNA methylation is one of the most highly conserved and studied chromatin modifications. Aberrant DNA methylation has been shown to compromise tissue development and homeostasis and cause human developmental disorders as well as cancer. Yet how DNA methylation is established and maintained remains incompletely understood especially at non-coding intergenic regions. We recently published that a histone mark, di-methylation of H3 lysine 36 (H3K36me2), is essential for recruiting the DNA methyltransferase DNMT3A and intergenic DNA methylation. Quite remarkably, germline mutations in DNMT3A and NSD1, the enzyme for generating H3K36me2, define two human childhood overgrowth syndromes that are phenotypically similar. Therefore, our findings suggest that aberrant intergenic DNA methylation may be central to the pathogenesis of these developmental disorders. We are eager to find out how!    

Technology:

What are the model systems that your lab is using?

We mainly use mammalian cell cultures (cell lines and primary stem cells) for our studies but we also actively collaborate with other labs to extend our findings to model organisms.

What are the key techniques that your lab is using? Are you open to training scientists from other labs?

There are two sets of techniques we rely on. One is epigenomic: we routinely perform ChIP-seq, ATAC-seq, whole-genome bisulfite sequencing and other technologies to profile the chromatin landscape at genome-wide level. The other is Crispr/Cas-based genome- and epigenome-editing: we use these powerful tools to perturb the chromatin landscape, often in a massively parallel manner for forward genetic screens. We are of course open to sharing our expertise with other CSCI labs.

Training:

What's your best approach to mentoring trainees in the lab?

We are a young lab so I consider myself as a “super-postdoc”, basically a postdoc with extra duties. Since I am actively involved in the science and day-to-day operations of the lab, a lot of the mentoring happens in the form of small talks or working alongside at the bench. In addition to more formal one-on-one meetings, I believe these casual interactions are critical as they help me know everyone better, understand their needs and foster a collaborative and dynamic culture in the lab. 

Who were your most influential mentors/role models in science and what did you learn from them?

I am fortunate to have been trained with great mentors. Among the things I have learned from my PhD and postdoc advisors, I would say their views about the importance of “people” in science are probably most influential for me. No matter what is your research area, there is a small community of scientists you will be interacting with throughout your career. Therefore, it is important to be a responsible and collaborative citizen since a good reputation will serve you well in the long term.

Can you recommend courses/lectures in Columbia University that would be most beneficial for students/postdocs?

If I can recommend anything outside Columbia University, I like the career development workshops and resources offered by New York Academy of Sciences. I learned a great deal during my postdoc training and it is also an opportunity to network with researchers from local universities and biotech companies.  

What would be your career advice for students/postdocs?

Science is a life-long learning process. Especially with the pace of recent technology innovation, it is important to keep an open mind. “Stay foolish, stay hungry” to quote Steve Jobs. I am learning from everyone in the lab and it is fun and inspiring. 

Lab management:

How do members of your lab celebrate accomplishments?

We are a group of foodies so we will find any excuse to get a lab lunch/dinner at good restaurants.

Does your lab have any fun traditions?

I adopted a tradition from my PhD lab called “Goof Off day”. We will take a weekday off to do something fun. This year we will go to an “Escape the Room” game.

What is the key to running a successful lab?

I hope I will be able to tell you in a few years!

What was the most exciting part about starting your new lab?

There are so many exciting parts, but I have to say that learning and growing with the first generation of lab members is the most satisfying thing and offsets the equally many frustrating and exhausting parts about starting a lab.

CSCI:

What was the main reason of you joining CSCI?

The dynamic regulation of chromatin is known to be key for cell fate transition and maintenance. Accordingly, various enzymes involved in chromatin regulation have been found to cause human neurodevelopmental disorders. We want to work with other labs in CSCI to apply insights from our molecular mechanism studies to gain a better understanding of stem cell biology. Ultimately, we hope that these joint efforts can lead to chromatin-based therapeutic approaches for treating stem cell-related diseases.