Everything Everywhere All at the Liau Lab

新年快樂！

Happy belated (Lunar) New Year from the Liau Lab! It’s been a really busy past year for us, filled with both science and, well…not-science.

We are all Michelle Yeoh <3

From apple picking to ice skating, we’ve had lots of fun over the past year:

Apple picking, or as the kids like to say, Pick Apple-ing.

Breakfast for dinner at our favorite local IHOP.

Ice skating at the Fenway rink. Brian is a very “down-to-earth” PI.

Enjoying some soondubu at Kaju!

Olivia educates the group on grass jelly desserts at MeetFresh.

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Fun aside, we’ve also been hard at work. In fact, 2022-2023 has really been the year of the Liau Lab—well, at least publishing-wise ;) In case you missed our recent scientific work, here’s a quick summary of our papers from the past year. Note: this is continuing off of our previous blog post—go check that out for our recent publications on molecular glue degraders and more!

Lamina-Inducible Methylation and Hi-C (LIMe-Hi-C)

Chemical biology meets 3D genomics! We developed a new approach to simultaneously look at chromosome conformation, DNA methylation, and lamina positioning. Through this, we found and subsequently characterized intriguing Polycomb-marked subcompartments!

DNMT3A base editor scanning

The lab’s first base editor screen, using an innovative reporter approach to study a nonessential gene! We leveraged an endogenous methylation activity reporter to map sequence-activity relationships across DNMT3A. Following up our screen results, we found a noncanonical DNA binding role for the PWWP histone reader domain. What’s more is that our screening strategy can be applied toward other chromatin regulators!

CRISPR-suppressor scanning

Our lab’s official protocol for CRISPR-suppressor scanning is out in Current Protocols! If you’re interested in mapping drug-protein interactions and identifying resistance mutations, you’ll be interested in checking this out.

DNMT1 activity-based CRISPR scanning

CRISPR screens for allostery? Taking advantage of decitabine, an activity-based DNA methyltransferase inhibitor that is nearly identical to the cytosine substrate, we applied CRISPR-suppressor scanning to look for mutations impacting allostery. We found some interesting ones causing DNMT1 hyperactivation. This paper also has some updated and improved analytical tools for analyzing tiling CRISPR screening data.

This paper is currently accepted in principle and we don’t have the pdf yet, but please enjoy our graphical abstract :3

PRC2 drug-addiction scanning

CRISPR screening a whole complex! We used CRISPR-suppressor scanning to systematically mutate the three core members of the PRC2 complex, discovering mutations that confer drug addiction. These pointed toward a model where lymphoma cells need to be in a “Goldilocks” state—too much or too little H3K27me3 is bad.

We had some fun creating art related to some of these studies, though unfortunately they weren’t selected by the journals for the cover/feature. Well, even if journals don’t appreciate our art, hopefully our blog readers will!

Nick, Allison, and Shelby collaborated to make this artistic representation of our LIMe-HiC method. The lime cross-section represents the nucleus, and the red represents GpC methylation.

Nick made this design representing DNMT3A base editor scanning. The pins represent loss-of-function mutations scattered across DNMT3A, and the compass is an homage to base editing.

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This past year also saw some new faces arriving in our group. We welcomed the skilled organic chemist, Dr. Stefan Harry, as a joint postdoc with the Bar-Peled lab at MGH. Additionally, we said hi to Tobias Hansen, a visiting graduate student from the University of Copenhagen!

Dr. Stefan Harry

Tobias Hansen

We also welcomed three (count ‘em, yep, we’re popular) new CCB graduate students to the lab:

Calvin Hu

Marc Anthony Zepeda

Idris Barakat

In more bittersweet news, we said goodbye to our longtime lab administrator Rebecca. We’re sad to see her go, but luckily she still works in the department so we can say hi :) On the bright side, we welcomed Lizzy Swenson as our new lab administrator, and have had a great time getting to know her!

Rebecca Stillo

Lizzy Swenson

Continuing with bittersweet departures, our lab has experienced some turnover in our researchers as well. Earlier in the year, we had three talented scientists move on to their next positions:

Pallavi, our first biologist postdoc and a stellar scientist, is now a Senior Scientist at Merck. Pallavi launched the protein biochemistry side of the lab and has provided invaluable expertise to numerous projects. More recently, she led our lab’s study applying CRISPR-suppressor scanning to investigate molecular glues.

Jiaming, a superb synthetic organic chemist postdoc, recently returned to California as a Senior Scientist at Ideaya Biosciences. He served as a mentor and wellspring of expertise for many during his time here, and synthesized a huge number of vital compounds, leaving a lasting mark on our lab (and our freezers).

Sam, a talented research assistant, is now attending medical school at the Cleveland Clinic, Case Western Reserve University! Sam was instrumental in biochemically characterizing DNMT1 mutants and also contributed to numerous other projects.

Check out these videos from Jiaming and Sam’s farewell party, by the way:

You may have seen our last blog post, but we also had four talented graduate students defend (Ally, Kevin, Allison, and Amanda). (*suppresses sobbing*)

Kevin Ngan, Ph.D. Kevin is now working at Tessera Therapeutics.

Allison Siegenfeld, Ph.D. Allison is now doing a postdoc in Prof. Karen Adelman’s lab at HMS.

Amanda Waterbury, Ph.D. Amanda is continuing in our lab as a postdoc for the near future.

Ally Freedy, Ph.D. Ally is now finishing the M.D. part of her M.D.-Ph.D. training at HMS.

With so much going on, 2023 has arrived sooner than any of us expected. But you know what? We have even more cooking, science-wise. Stay on the lookout for the YEAR OF THE LIAU LAB, PART 2!

Publications, Preprints, and PQEs—Oh My!

It’s a bird!… It’s a plane!… no… It’s the latest—

LIAU LAB BLOG POST !!!

Did you miss us? It’s been a hectic year for us, but we are so excited to share the work we’ve been up to. We’ve had a lot of things in the works and 2022 is shaping out to be the year that we unleash the flood on the scientific community. Ready or not, here we come!

Keen followers of our website might have noticed some changes recently. We’ve revamped our website, for starters, and what’s more, we’ve dropped some new publications. Let’s take a quick stroll through them…

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But first of all we have an important announcement to make. The big man himself has finally joined the twittersphere! Help us get him to 1,000 followers (or at least to another fun number before that)!

Please like + subscribe! <3

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Now back to what you’re here for. Without further ado, here are our lab’s peer-reviewed publications from the past year! Click on the pictures to go to the journal site.

The exciting sequel to 2019’s Park et al. paper! We synthesized improved cycloheximide derivatives and collaborated with the Shao lab to perform cryo-EM characterization. A multidisciplinary study spearheaded by Yumi and Eileen.

Drug resistance sounds scary but it’s actually been a driving force for biological discovery. Ally wrote an insightful review on the history of drug resistance alleles and their utility for science moving forward.

Our New Year’s present to the chemical biology community in the form of CRISPR-suppressor scanning with molecular glue degraders. Sounds like a sticky problem, right? But it was no match for Pallavi, Kevin, and the rest of the team!

But wait, there’s more! We have not one, not two, not even three, but four additional stories out on bioRxiv as of today. They’ll be out in journals sometime soon* but if you’re dying to take a look, click on the images below!

*soon: sometime in the next decade, probably (you know how peer review is)

Finally, we are proud to say that all three of our CCB grad students this year passed their PQEs (preliminary qualifying exams) with flying colors! We celebrated with some champagne, though not without some technical difficulties…

Congratulations to Megan, Olivia, and Nicholas!

Anyway, that’s all for today! Keep your eyes peeled for more exciting Liau Lab work just around the corner….!

Virtual Liau Lab

A stillness outside
They gather indoors and think
Thank heavens for zoom

We hope you and your families are all staying healthy and as safe as possible during this uncertain time. Like many others, we in the Liau Lab are doing our part to slow the spread of SARS-CoV-2 by working from home and practicing social distancing. With a pandemic loose, it’s imperative that we all follow the recommendations of our public health officials.

And yet it’s also important to do what we can to stay positive and connected in this time of crisis. In that spirit, we’d like to present this blog post as a glimpse into the little joys of day-to-day quarantine life. Without further ado:

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S T A Y H O M E

an acrostic poem & visual journey

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S — Socializing VIRTUALLY

To stay in touch with others and safeguard our mental health, we’ve been meeting up each week over Zoom to chat and socialize over coffee. Many thanks to Ally for taking the initiative to coordinate these virtual coffee hours!

We may not be essential, but caffeine sure is.

T — TASTY CREATIONS

If there’s one thing that brings our lab together, it’s a love for food, and we have some amazing chefs. Take a look at some of the dishes we’ve made over the past few weeks:

Matzah lasagna made by Allison for Passover. We wouldn’t pass over this dish!

Ramen and scallion pancakes made by Cindy. The dishes are arranged like a water molecule.

Lentils from Pallavi. Have you tried cooking in an Instant Pot?

Potatoes from Pallavi, cooked to goldenrod deliciousness.

A hearty mac and cheese dinner made by Ceejay.

Cinnamon rolls with cream cheese icing made by Nick.

French toast made by Cindy. Look at those swirls!

Pizza made by Cindy. Looks like the toppings have undergone phase separation.

Dalgona coffee made by Hui Si. Beautiful and trendy, just the way we like it in the Liau Lab.

A — ANIMAL FRIENDS

More time at home means more time to spend with our furry pals! Rebecca shared some adorable pictures of her dog, Molly, enjoying her time at home:

Molly posing under a table.

Even dogs can Zoom!

In the midst of the pandemic, we were excited to welcome Emma to the lab as our newest graduate student! Well, excited mostly because now we have access to cute pictures of her adorable cat, Linus. After all, grad students are temporary, but cat pictures are forever.

Welcome to the Liau Lab, Emma and Linus!

Linus posing just for you.

Y — YEARNING FOR THE OUTSIDE WORLD

such good girl am i
now the hooman never leaves
take me on walks tho

Same, Molly, same.

H — Honing the ancient craft of breadmaking

Given the recent nationwide uptick in baking, it’s no surprise that some of our very own lab members have decided to try their hands at making bread. The Liau Lab’s bread and butter, so to speak, are E. coli and human cancer cell lines, so it’s a pretty big deal to see our lab venture into working with yeast.

Ally’s sourdough starter. Does culturing yeast fill the void left by not doing TC?

Sourdough goodness courtesy of Ally. Look at those designs!

More sourdough courtesy of Emma. Notice the pattern in the bread. Like snowflakes or DIY masks, no two loaves are identical.

A fluffy loaf with that classic corgi look, courtesy of Shelby. Shout out to Ally for an emergency contactless delivery of yeast and flour.

O — ONGOING CHOCOLATE ADDICTION

As you all know, our lab really likes chocolate. Just because we’re not in lab, doesn’t mean that addiction went away…

You can tell that Allison baked this banana bread, because it’s clearly just a vehicle for chocolate.

They say to work from home effectively, you need to recreate your office environment. Enter Ally, who decided to recreate the the lab chocolate bowl at home.

M — MEMES

You know we like memes in the Liau Lab. Well, here’s one we concocted at the beginning of the year:

Get you a lab that can do it all.

Meanwhile, some of us are having a little too much fun with the Zoom custom backgrounds…

“This is fine.” Out of the mouths of babes.

E — ENGAGING WITH SCIENCE

They say that cooking is really just science at its heart. Well, Jiaming traded in his round-bottom flasks for some nonstick pots and has been culturing his own yogurt. Testing different brands of milk and carefully varying the freshness of his yogurt starters, he concludes that “they all produce tasty yogurt in different textures and flavors.” Can’t argue with a postdoc.

Homemade yogurt from the Li Test Kitchen. The nice thing about home cooking experiments is that the CCB safety officer will never know if you’re wearing safety glasses or not.

As a lab, we’re also trying to stay engaged with science a little closer to our research. As part of this, we’ve been having weekly journal clubs to cover recent developments and historically important papers in our research areas.

Here’s a view into our virtual lab meetings. Shout out to Shelby and Hui Si for an awesome journal club presentation!

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And that’s all for now. We hope this brought some joy into your day, and thanks for reading! We wish you and your loved ones safety and security.

While we’re sad to be out of the lab for now, we know it’s for the best. We look forward to returning to our benches and hoods in the future so that we can bring more science to you all. Until then (or until our next update), take care!

Spring is blossoming
We wait in a fractured world
For the next blog post

Summer Shenanigans

Ahh, September. A month of change that ushers in the fall, also known as pumpkin spice latte season. As the floodgates open and unleash a deluge of undergrads, G1s, and tourists back into Harvard Square, the members of the Liau Lab can be found right where they have been all along: sipping iced cold brews and snacking on veggie straws in the air-conditioned confines of Converse 201.

It’s been a packed summer, filled with both working hard and hardly working. Here are some highlights:

• The lab receives a sweet grant courtesy of the Ono Pharma Foundation (thank you for the support!)! Those of you who check our website might have already seen the announcement sneakily go up on our front page news ;) Keep checking, we may have more good news to share in the future…

Thank you to the Ono Pharma Foundation!

• And the lab got bigger, too. Over the summer, we welcomed Rebecca Stillo, our new lab administrator; Aiden Wang, who joined us as a post-bacc from Cambridge (not that Cambridge, that Cambridge); David Tanner, a rising sophomore at Harvard; and Claudia Gomez, who was visiting us from Miami as part of the Summer Research Opportunities at Harvard program!

Check out Claudia’s poster on her work studying LSD1 biochemistry with Amanda!

• And of course, shout-out to Sarah, who’s been working hard under the tutelage of Ally and Hui Si and doing lots of tissue culture, western blots, and more. Finishing off a very productive summer, she gave an excellent talk at the PRISE program symposium!

• We also had another GROUP CLEANUP. It was hard work, but our freezers are now defrosted, our fume hoods so clean you could eat off of them (NOTE: to any safety officers reading this, that was a joke), and our lab inventory is so comprehensive it spans numerous google spreadsheets. Suffice it to say that we emerged victorious over entropy. To celebrate, we headed on over to Aeronaut’s beer garden to relax.

Brian is many things, but “selfie king” is not one of them.

Hui Si’s “postdoc hands” in action.

• And with that, summer is over and fall is here. We’re looking forward to seeing what the rest of the year will bring. Any G1s reading this blog? If so, we’ll point you to our Open House later this month on 9/20. We’ll have everything you could possibly want: free food, dank memes, alcohol, and more free food. Raise a glass.

• We’ll leave you with one final nugget of wisdom from Professor Liau himself:

Ally and Kevin present at the Broad!

This morning the lab had the exciting opportunity to present at the Broad Institute’s Cell Circuits and Epigenomics meeting! Ally and Kevin served as our representatives, talking about their work studying LSD1 and DNMT1, respectively.

Ally talks about our lab’s work studying the lysine demethylase, LSD1. If you haven’t already, check out our paper in Nature Chemical Biology!

Kevin fields questions from an eager scientist after his talk.

Many thanks to Cell Circuits and Epigenomics for including us in their community and letting us share some of our exciting findings. Until next time!

Let’s hear some applause for our speakers!

A new chapter for the Liau Lab

With our group practically doubling in size over the past year, it was about time for us to take a new group photo. Many thanks to Beverly Fu from the Balskus lab for helping us with the shoot! After many failed attempts marred by blinking eyes and blocked faces, we finally got a good shot, full of smiles and Brian’s signature "boss” pose.

If you follow us on twitter or have been obsessively checking our website (who could blame you?) you may have noticed some updates over the past few months on our publications page. That’s right – the lab’s first two papers are out in Angewandte Chemie International Edition and Nature Chemical Biology. Click on the paper titles above to check out these awesome works, which really showcase two of the major and ongoing focuses of our lab.

The LSD1 project was (and still is) a huge, interdisciplinary endeavor that required the coordinated efforts of many members of our lab (as well as collaborators) in a diverse array of fields. Here, the core members of the LSD1 team celebrate a hard-won success. Congratulations!

In the midst of these exciting events, we’ve unfortunately had to say goodbye to our wonderful laboratory manager, Larry Valles, who has moved on to serve as a Junior Operations Manager for Immunology, Microbiology, and Genetics at Harvard Medical School. While we’ll miss him, we’re also happy that he has accepted this great opportunity and wish him the best! We’ll always remember Larry for supporting us through the trials and tribulations of research.

Larry (a.k.a. “molecule”), purveyor of doughnuts and bagels and harbinger of diabetes.

In a bittersweet way, 2019 is proving to be a big year of change for the Liau lab. We’re looking forward to everything the future has to offer, and we can’t wait to share more of our scientific and non-scientific exploits with the world!

Fall 2018 retrospective

Happy New Year from the Liau Lab! It’s been quiet in the lab the past few weeks, but we’re starting to get into the gear of the new year. In the spirit, however, of holiday season reflection (and since a blog post is severely overdue!) we’ll be taking a look at some of the highlights of fall 2018. Buckle in, cause it’s gonna be a long ride.

First up, the Mid-Autumn Festival! The group celebrated with some tea and mooncakes, courtesy of Cindy.

Not too long after that came another reason to celebrate, when Ally passed her preliminary qualifying exam! Congratulations, Ally!

Speaking of celebrations, we all got more than our fair share of cake with all the birthdays happening in the fall…

For Thanksgiving, Brian graciously welcomed us to his home for a potluck party. As with all potlucks, the quality of the experience is only as good as the quality of cooking your guests can achieve, but luckily for us, we have lots of talented chefs in our lab!

Warning: don’t view the following slideshow on an empty stomach…

…it was a fun night. Of course, in addition to all this eating, we did manage to get some work done. Our lab loves next-generation sequencing, but it’s not every day that we buy a brand new kit. As Kevin found out, they come packaged in huge boxes. Big boxes for big science, right?

As many of you might know, one big focus of our lab is studying the 3D organization of the genome. It’s not something you think about every day, but how the cell fits 2 meters of DNA inside its nucleus is pretty mindblowing. We got the opportunity to share our science with local students, crafting some interactive displays to help illustrate what we do and why we do it. Thank you to the Harvard Ed Portal, and to Brian, Shelby, and Allison for organizing this!

To close out 2018, we enjoyed a holiday party hosted by Brian, where we once again ate plenty of food. Highlights of the evening included a 2018 year-in-review slideshow, as well as a rousing game of white elephant. Here are some highlights from the evening:

And here we are, at the beginning of another year. As we all try to shake off the holiday stupor and get back to work, one thing’s for certain: the new year has much more food in store. After all, we are the Liau Lab.

And with that, thanks for reading! We’re looking forward to some exciting stuff in 2019, and we can’t wait to share it. Until next time :)

Tissue culture champions

Science can be a lot of work. Thankfully, we have grad students for that.

Kudos to Mike and Ally for carrying this screen to the finish line!

We've moved into our new home!

Check out our new lab! We have two large laboratory rooms as well as a graduate student office space, and a break room. We're pretty much settled in at this point, so now it's time to do some science! Pictured in the tissue culture room is the inagural passage of 293Ts. A postdoc in the background can also be seen setting up the very first chemical reaction of the new lab!

Synthetic chemists enter tissue culture

As any synthetic chemistry lab does, we all appreciate a high enantiomeric or diastereomeric excess. However, generating multiple substrates in one flask has proven to be quite useful as YP and Amanda begin to test some of the compounds that they have been working on over the past few months. Also pictured in the foreground is Kevin, who is, in general quite excited about biology.  Cindy is also in this picture somewhere...

Winter Has Arrived in Cambridge

We've been preparing for hibernation this winter by bulking up with chocolate and food at various holiday parties. One of the well-known caveats of joining an interdisciplinary research group is access to multiple department holiday parties.

In addition, the first-year graduate students (aka G1s) have been settling nicely into the group since officially joining in December. As Brian's first round of students, it is an understatement to say that we are excited to help create a culture that will last for years to come. For those of us that are interested by the history of the department, it has been quite the pleasure to work in the space of what used to be the storied lab of Prof. Dave Evans. However, we are very much looking forward to moving into our new space in just a few months (pictures will follow!).