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.

---

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.

---

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!

Happy Holidays from the Liau Lab!

Season’s greetings from your favorite chemical epigenomics lab ;)

This New Year’s Eve, we in the Liau Lab hope that you, your family, and your friends continue to enjoy your holidays and have a great start to the new year! It’s been a year full of challenges and new experiences for all of us, and we owe so much to the healthcare workers, public health officials, and everyone else who has worked to control the pandemic. We are thankful for have had the opportunity to continue our research this past year and beyond :)

Like many others, our lab has been divided into shifts: a morning shift and an evening shift. Luckily for us, we all got to choose the shift that more or less best suits our sleep schedules (or, um, lack thereof). Unsurprisingly, there’s a bit of a difference in the types of people that self-sorted into the two shifts…

Spot-on assessment from Emma. Please note the Comic Sans.

Fig. 1: Representative screenshot illustrating significant morning shift wholesomeness (p < 0.05).

Fig. 2: Representative screenshot illustrating evening shift degeneracy. Results are, of course, not significant.

To help us get accommodate more lab members while still staying at a safe density, our lab was fortunate to annex some new lab space. Take a look!

Thank you to the lab members that graciously accepted banishme— temporary relocation to our annex spaces!

Zoom fatigue? What’s that?

Of course, in an era of distancing and virtual meetings, we’ve been trying to figure out ways to stay connected to each other. Beyond zoom coffee hours, some lab members organized a virtual social over Thanksgiving weekend, where we got to battle for glory in some online games.

Hui Si Kwok, master of deception. Turns out postdoc hands can be used for passaging cells or wiping out your crewmates.

Playing codenames!

Though it was a challenge to adapt our annual holiday party to Zoom, no pandemic was going to get in the way of celebrating another year in Liau Lab history. Thanks to Ceejay for planning this event, and to Emma and others for stepping up to make the annual Year in Review presentation…

it’s fine

Virtual partygoers!

The boss posing with his holiday gift from the lab.

As is traditional, we had a little competition for lab members. This year, Ceejay organized a rousing game of “Brian Bingo”: the game where you predict things Brian will do over Zoom and assemble your own dream bingo board out of them. Although no one got a real bingo, Shelby came the closest. Here’s a look at her winning board:

Red indicates correctly predicted Brian-isms. 5 plus the free space, not bad!

So there you have it! It’s been a long year, and we’ve had our ups and downs, but whether we’re resting or working, we’re trying to do our best to prepare ourselves for the new year.

We’ll leave you with some mouthwatering desserts from Allison’s kitchen:

Allison’s pecan pie.

Allison’s (vegan) pumpkin cheesecake.

Trust us, we’ll need the sugar to get us pumped for the new year. It’s truly been an experience living through 2020, but we’re excited to see what 2021 brings. Until next time, and stay safe!

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:

---

S T A Y H O M E

an acrostic poem & visual journey

---

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!

---

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:

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 :)

Hello there fall!

Charging head first into the new year. It's been a while since our last blog post, but that's not to say the last few weeks haven't been eventful. Besides running experiments, making figures, and submitting grants, we've been up to a lot. Check it out below!

With teaching, classes, rotators, and more awaiting at the start of the academic year, the lab celebrated the waning summer days with a trip out of Cambridge to get dim sum and boba. Despite the challenge of identifying vegetarian-friendly items (not trivial when it comes to Chinese food), we all left with full stomachs. It was even some people's first time trying boba!

As August turned into September, we had another festive occasion: Amanda's birthday! Since she's not a huge fan of cake, Brian bought some pies from a local bakery, Petsi Pies, to help celebrate.

Now that the academic year has begun, we're all steeling ourselves for a busy semester. Recently, posters have been popping up around the chemistry department advertising the fall open houses for different labs. Ours is still quite a while away, but we couldn't resist pinning up some posters in the meantime. We'll leave you with our teaser:

Summertime group bonding

It's been quite an eventful week. Between reorganizing group responsibilities, cleaning the lab, kayaking on the Charles, and engaging in gluttony in the backyard of Harvard Divinity School, our stamina has truly been tested. However, despite the strain on our minds and backs, we all had a blast.

Tasty.

Kevin rests his aching body during the cleanup.

First up on the docket: reorganizing and cleaning the lab. Although fighting entropy is no small feat, we were fortunate that our very own Kevin Ngan was among those leading the charge. Several meetings and a full day's worth of cleaning later, we ended up with a myriad of spreadsheets, room upon room of labeled drawers, and a defrosted -80˚C freezer to show for our efforts.

To gather supplies for our upcoming barbecue, we naturally turned to Costco. It was quite the adventure.

Shopping at Costco.

We bought a lot of food.

Next, taking advantage of the summer sun, we went kayaking on the Charles River. With the barbecue looming later that night, it was probably a good idea to get some exercise in. Many thanks to Ally for spearheading this outing!

The group poses on dry land.

The group poses not on dry land.

Wholesome undergrad friendship.

The boss kicks back while the grad student rows.

Of course, the highlight of the week was our potluck barbecue. While our lab is normally fairly health-conscious, we put aside our better judgments to enjoy the night.

The party begins.

Grillmaster Brian.

And that's it! We're all back to our benches (or hoods) now, hard at work. Be on the lookout for some scientific news in the near future :)

...and if you're not tired of seeing our faces, check out the rest of the pictures below!

Thinking outside the box...

Panini press yields improved flavor profile to doughnut

Abstract
Another week, another box of doughnuts, this time as a reconciliation gift from our chronically late pipette tip supplier. Naturally, we slapped it on our panini press.

Methods
We slapped some doughnuts on our panini press.

Results

Figure 1. We consume a lot of sugar in this lab.

Figure 2. First authorship goes to the boss himself. "how do you think I got this job? I think outside the box" –Brian B. Liau, 2018

Figure 3. Image is representative of two independent experiments.

Conclusion and Future Directions
The results of this study are highly promising, indicating that this method may have widely applicable utility. Future studies will assess how panini press grilling influences the enjoyability of alternate flavors of doughnuts, as well as other dessserts.

Sweet summer days in the Liau Lab

Good PIs and departments know that donuts are the fuel for excellent research. Our newest three graduate students received a warm welcome with Union Square Donuts twice in one week! With all the sugar going around, it looks like the lab is in for an energized summer brimming with science.

Enjoying donuts and cold brew coffee courtesy of the GPC of the Chemistry and Chemical Biology department!

Donuts from the weekly farmer's market provided by the Principal Investigator himself. In the background, you can spy some of the pretzels the lab is addicted to, along with a set of chopsticks for mess-free eating.

Research at the Interface of Chemistry and Biology