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Caleb Lareau Profile
Caleb Lareau

@CalebLareau

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Assistant Professor at Memorial Sloan Kettering. Interested in computational and translational immunology. cat dad.

New York, New York
Joined October 2015
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@CalebLareau
Caleb Lareau
11 months
Some big news: I’m absolutely delighted to announce that I will be starting my group this fall in the Computational and Systems Biology Program at @MSKCancerCenter in New York City! 1/
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@CalebLareau
Caleb Lareau
2 years
Encephalitis caused by human herpesvirus 6 has been repeatedly observed in CAR-T cell case studies and clinical trials. In a new work with @satpathology , we make the surprising observation that the cell therapy itself may be the source of lytic virus. 1/n
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@CalebLareau
Caleb Lareau
3 years
Out now in @NatureBiotech , ASAP-seq and DOGMA-seq!! Together with @emimitou , @psmibert , Kelvin Chen, Shimon Sakaguchi, @LeifLudwig , @bloodgenes , Aviv Regev, and many others, we are thrilled to share out the latest in single-cell multi-omics!
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@CalebLareau
Caleb Lareau
7 months
Out today in @Nature , we describe HHV-6 reactivation in T cells, including therapeutic CAR T cells. I’m so grateful to have worked with an all-star team during my time in the @Satpathology lab that led to these findings. 1/n
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@CalebLareau
Caleb Lareau
11 months
Out today in @NatureGenet , our work utilizing single-cell multi-omics to define specific immune cell subsets that experience purifying selection against pathogenic mitochondrial DNA. Check out a thread about this work below: 1/22
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@CalebLareau
Caleb Lareau
1 year
Out today in @NatureProtocols , our detailed writeup on the mitochondrial scATAC-seq assay, spanning everything from the molecular biology to computational analyses. Check out the paper here: and some highlights in this thread: (1/11)
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@CalebLareau
Caleb Lareau
2 years
Co-first dance with @isabelfulcher ! After 25 months under review, it's official!
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@CalebLareau
Caleb Lareau
1 year
Very inspired by this paper-- I don't think I've ever seen anything like this. I've never been able to lineage trace (with mtDNA) mutations any system over this time span, so I took a peak at the GEO data and found something potentially interesting? 1/n
@Masopust_Vezys
Masopust Vezys Lab
1 year
Authored by Andrew G. Soerens et al, we show that #Tcells are capable of proliferating in response to iterative stimulation for over 10yrs! And produce enough progeny to occupy a volume 30,000x the Earth's volume! @Nature
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@CalebLareau
Caleb Lareau
2 years
Wow! I am honored to be in the company of amazing #ForbesUnder30 honorees. I could not have made it this far without the support of awesome mentors, peers, and friends. Check out our awesome cohort here:
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@CalebLareau
Caleb Lareau
9 months
Come be my colleague! We are hiring a faculty member in the Computational and Systems Biology Program @MSKCancerCenter . If you are on the market and want to learn more about MSK or the csBio program, I’m happy to share my wonderful experiences here!
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@CalebLareau
Caleb Lareau
1 year
Update on the clonality analysis: now with TCRs! Thanks to @BenceDaniel2 , @InflammatoryDC , and @Satpathology for the push... I'm seeing a massive clonal bottle beck in the data At around immunization 9, we start to see a single TCR-B take over at ~70% of the population...
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@CalebLareau
Caleb Lareau
1 year
Very inspired by this paper-- I don't think I've ever seen anything like this. I've never been able to lineage trace (with mtDNA) mutations any system over this time span, so I took a peak at the GEO data and found something potentially interesting? 1/n
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@CalebLareau
Caleb Lareau
3 years
I'm genuinely excited to see the extension of methods to discern clonal structure from mtDNA variants-- something that I've thought about over the years. However, I'm going to comment on a couple of points in this pre-print to hopefully show why mtDNA tracing isn't easy 1/n
@YuanhuaHuang
Yuanhua Huang
3 years
MQuad preprint is up. It effectively detects mitochondrial variations for clonality analysis. We saw mtDNA variants are often complementary to nuclear SNVs or CNVs. Check it out with your scRNA, scDNA or scATAC data.
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@CalebLareau
Caleb Lareau
2 years
So pumped to be out of stealth 🥷 Cartography has an exceptional vision for the future of immunotherapies and an all world team to execute! Checkout our launch here! @satpathology @krparker @HowardYChang @MaxMumbach @JeffreyVerboon
@CartographyBio
Cartography Biosciences
2 years
We’re excited to officially launch Cartography Biosciences today with $57M in initial financing. With this support, we will create a smarter roadmap for #cancer immunotherapies with our precision antigen expression atlas. 🧵 #Oncology #MedTwitter
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@CalebLareau
Caleb Lareau
4 years
Impressive work from the @satijalab introducing Seurat v4! That said, I'm even more excited for Seurat v14, where an entire human cell atlas will almost certainly (r^2 = 0.96) be introduced with the publication. I have no doubt that @NYGCtech is up to the task!
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@satijalab
Rahul Satija
4 years
We are excited to release: * Our new preprint on weighted nearest neighbor analysis to define cell states based on multiple modalities in Seurat v4 * A multimodal CITE-seq dataset of human PBMC w/200k cells and 228 antibodies Data/code are available now!
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@CalebLareau
Caleb Lareau
1 year
Delighted to highlight SEACells-- a fantastic new method from the labs of @SettyM and @dana_peer -- in @NatureBiotech today. Work smarter, not harder, with your #scATACseq and #scRNAseq data.
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@CalebLareau
Caleb Lareau
3 years
Are you interested in completing your postdoctoral work at @Stanford ? We are hosting a Stanford Science Fellows webinar from noon-1pm on September 9th-- come hear about the program and get your burning questions answered!
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@CalebLareau
Caleb Lareau
5 years
Big innovations in scATAC-seq out in pre-print today. First, our paper with @fabianamduarte , Jen Chew, Vinay Kartha, and others at @BioRad and advised by @JD_Buenrostro describes significant technical innovations in data quality, cell capture, read abundance, and informatics. 1/4
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@CalebLareau
Caleb Lareau
3 years
Thrilled to see this collaborative work out in @SciImmunology led by @JessicaWang927 and @gardnerlabUCSF at @UCSFDC and Stanford in the @Satpathology lab
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@CalebLareau
Caleb Lareau
1 year
when @satijalab puts mito on the #singlecellgenomicsday shirts but you're in California
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@CalebLareau
Caleb Lareau
4 years
Just me, Larry, and Boo. #ClassOf2020 #PhDone
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@CalebLareau
Caleb Lareau
2 years
Thank you @statnews for the incredible honor and for the opportunity to attend #STATSummit . I'm so excited to meet the other #STATWunderkind honorees this week in Boston!
@DrewQJoseph
Andrew Joseph
2 years
It's here! Our sixth class of @statnews Wunderkinds, those early-career researchers and doctors already making waves and headed for even bigger things
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@CalebLareau
Caleb Lareau
4 years
While all of this is fun and good, one has to ask themselves, "if you can't summarize your paper in a meme, is it even worth writing?" Fortunately, we can. I'm sure that even @MCHammer would agree that #asapseq is the future. Enjoy! 6/6
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@CalebLareau
Caleb Lareau
11 months
Our lab will be hiring at all levels for both experimental and computational positions! Please reach out or find me at #HCA2023GM if you have an interest in joining, collaborating, or have any advice for a new PI! 5/fin
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@CalebLareau
Caleb Lareau
4 years
The team of @emimitou and @psmibert make it look easy. This assay went from idea to proof of principle to biological insights in a matter of weeks... unreal efficiency and innovation from @NYGCtech 1/6
@NYGCtech
NYGCtech
4 years
Excited to share our latest single cell multimodal assay. ASAP-seq pairs surface and intracellular protein detection with high quality chromatin accessibility on the @10xGenomics #scATACseq platform.
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@CalebLareau
Caleb Lareau
11 months
Thank you to the exceptional colleagues that shaped my scientific journey, esp. @satpathology and @anshulkundaje for opening their labs to me at Stanford; @bloodgenes , @jd_buenrostro , and @LeifLudwig for training me in my PhD. It’s exhilarating to join their ranks as a PI. 4/
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@CalebLareau
Caleb Lareau
2 months
In addition to our preprint, we’ve released all code, data, and step-by-step protocols to get started immediately PERFF-seq. We think this will be readily adoptable, and we would be grateful for feedback! 16/n
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@CalebLareau
Caleb Lareau
4 years
We are hiring a Life Sciences Research Professional here at @StanfordMed ! Come work with me and @Satpathology to apply cutting edge single-cell genomics assays to understand fundamental properties of disease!
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@CalebLareau
Caleb Lareau
2 years
A toast to the newly minted Dr. @julirsch ! So thankful to have you as a friend and colleague. May your mitos be plentiful and your Q30 scores be high on this monumental day #cothrist #fine #map #EarthDay #catdad
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@CalebLareau
Caleb Lareau
2 years
A tour-de-force effort from (Dr.!) @TimoRckert and @RomagnaniLab characterizing (clonal) adaptive immunity of NK cells IN HUMANS! So happy to have worked with this team on this fascinating problem. Check out this thread to see how single-cell multi-omics enabled these🔥insights.
@RomagnaniLab
Romagnani Lab
2 years
We are excited to share our recent paper with the title “Clonal expansion and epigenetic inheritance shape long-lasting NK cell memory”, led by @TimoRckert , in which we study the origin and maintenance of human adaptive NK cells!
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@CalebLareau
Caleb Lareau
1 year
At around immunization 20, it appears that a missense variant in the Mt-cytb protein (m.14193T>C / p.17S>P) massively expands and takes over the T cell population throughout the remainder of the experiment 2/n
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@CalebLareau
Caleb Lareau
1 month
Check out this awesome digest on PERFF-seq from @tsion_abay about our time developing it in the @Satpathology lab!
@10xGenomics
10x Genomics
1 month
Work with rare or difficult to sort cells? Don’t miss this blog post! Learn about PERFF-seq, a new method for RNA-based enrichment of cells prior to scRNA-seq with Chromium Flex, and read valuable insights from method co-developer @tsion_abay .
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@CalebLareau
Caleb Lareau
3 years
@10xGenomics Thanks for the highlight! mtscATAC-seq was co-lead by @LeifLudwig while we were at @broadinstitute @BostonChildrens @harvardmed working with Aviv Regev and @bloodgenes . It takes a whole team to hack a problem like this!
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@CalebLareau
Caleb Lareau
2 years
Despite the truly remarkable success of cell therapies, patients have been recurrently diagnosed with unexpected side effects, including neurotoxicity. A recent paper in NEJM brought HHV-6 encephalitis into the foreground of one of these toxicities. 2/n
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@CalebLareau
Caleb Lareau
1 year
I'd be surprised if this was indeed a functional variant, but I am curious about if over this experiment that somatic changes (in the mito genome or otherwise) helped confer a selective advantage for a subset of the cells during some transfer/bottleneck? 4/n
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@CalebLareau
Caleb Lareau
4 years
@anshulkundaje @vallens @RongxinFang Currently void of content, but now in progress... Database (comment only; please DM if anyone wants to help curate): Submission form (public):
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@CalebLareau
Caleb Lareau
2 years
Further, we note that this could easily happen in other viruses or other cell therapies. From our computaitonal screens, we identified HSV-1 reactivation (in iPSCs) and EBV reactivation as other potential latent viruses that may reactivate in various cell therapy contexts. 15/n
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@CalebLareau
Caleb Lareau
5 years
Awesome to see our work on mtDNA lineage tracing highlighted at @satijalab ’s #singlecellgenomicsday . Tune in to the live stream here:
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@CalebLareau
Caleb Lareau
2 years
Above all: we are very optimistic about the future of cell therapy. Latent viral reactivations can be manageable if diagnosed and treated accordingly. We hope that our work brings clarity to this source of toxicity in cell therapy settings and makes these treatments safer. 16/n
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@CalebLareau
Caleb Lareau
2 years
To do so, we first examined the landscape of human viral reactivation systematically. Using Serratus (), a peta-base scale atlas of viral expression, we examined viral reactivation against viruses that can enter latency, including herpesviruses. 4/n
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@CalebLareau
Caleb Lareau
2 years
What we found was a rare population of cells (about 1 in 300-10,0000) that express hundreds of HHV-6 UMIs that we term HHV6 super-expressors. These rare cells explained >99% of the expression of HHV6 in culture. 10/n
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@CalebLareau
Caleb Lareau
2 years
I use this workflow all the time-- for everything from gRNAs to antibody barcodes. It was instrumental in getting our ASAP/DOGMA-seq preprocessing workflows up and running quickly. Glad to see the preprint out!
@sinabooeshaghi
Sina Booeshaghi
2 years
In a new preprint, @lioscro , @JaseGehring , @lpachter and I describe a method and software (kITE) for quantifying orthogonal barcodes from assays such as Perturb-seq, Clicktagging, TAPSeq, CiteSeq, Multiseq, and 10xFeature Barcoding: 1/
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@CalebLareau
Caleb Lareau
7 months
If this paradigm appeals to you-- massive-scale data analyses to motivate experiments for new discoveries in cancer immunotherapy, my brand-new group at @MSKCancerCenter is hiring to pursue other questions in this framework! Please get in touch! 11/n
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@CalebLareau
Caleb Lareau
1 year
In any case-- very cool data @Masopust_Vezys -- thanks for uploading your sequencing to GEO to enable niche analyses like these!
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@CalebLareau
Caleb Lareau
4 years
@JeanMolinier2 @MicrobiomDigest @KamounLab @PubPeer It appears that the editor in chief of the journal is a co-author on the study fwiw
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@CalebLareau
Caleb Lareau
3 years
@JD_Buenrostro "Harvard professor replaces syllabus with tweet thread"
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@CalebLareau
Caleb Lareau
3 years
However, I felt like many points that were made in this preprint mischaracterized our prior work, so I felt compelled to write on a public forum. I'm more than happy to discuss mtDNA tracing/variant calling/etc. anytime. 25/25
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@CalebLareau
Caleb Lareau
2 months
What’s even better than a tweet thread? A YouTube live stream! Come learn about PERFF-seq, including assay development and performance, TOMORROW (3/29) at #singlecellgenomicsday hosted by @satijalab (my talk is at noon ET): 19/n
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@CalebLareau
Caleb Lareau
4 years
I moved across the country during a pandemic to start my fellowship at @Stanford . It's extremely disheartening to see faculty like @MLevitt_NP2013 and affiliates like @SWAtlasHoover use their platform at this university to push dangerous, un-scientific nonsense. What can be done?
@MLevitt_NP2013
Michael Levitt
4 years
How did emails sent to @ISCB_info 14 Mar. launch Lior Pachter @lpachter on his campaign of anti-science hate? Must be his fear! He needs to stop being so scared. It is not good for him or those who believe a word he says. DO THINK as if your life depends on it. IT DOES!
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@CalebLareau
Caleb Lareau
4 years
🔥🔥🔥🔥🔥 from @maple1989 . Amazing, tireless execution of a plan and a vision that's been years in the making. Awesome work!!!!
@saima_lab
Sai Ma
4 years
Our SHARE-seq paper for single-cell ATAC+RNA co-profiling is now in Cell! @CellCellPress
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@CalebLareau
Caleb Lareau
2 years
What caught our attention was that among viruses that can be reactivated in T cells, HHV-6B, an endemic virus emerged from our screen. As the receptor of HHV-6B is OX40, a T cell co-stim molecule– this implicated T cells as a source of virus. 5/n
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@CalebLareau
Caleb Lareau
2 years
I want to give a special shout out to my wonderful colleagues to made this work happen, including @majzner_lab , @satpathology , and others not on Twitter. Their boundless energy and creativity made assembling this story a very fulfilling experience. 18/n
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@CalebLareau
Caleb Lareau
2 years
The most critical data came in collaboration with an awesome teamwork with friends at @DanaFarber and @StJude . Here, we show that we can identify HHV-6B+, CAR+ T cells in vivo from patients receiving clinical and FDA-approved CD19 CAR-T cells. 12/n
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@CalebLareau
Caleb Lareau
4 years
First, @LeifLudwig and Christoph Muus figured out how to retain mtDNA in droplet-based scATAC, which we term mtscATAC-seq. This enabled scalable solutions for performing human lineage tracing using somatic mtDNA variation 2/n
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@CalebLareau
Caleb Lareau
2 years
Given the striking reactivation of HHV-6 in standard T cell cultures, we wondered whether HHV-6 reactivation was occurring during CAR-T culture. With terrific support from friends at @AllogeneTx , we studied the dynamics of HHV-6 reactivation in research CAR T cells. 7/n
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@CalebLareau
Caleb Lareau
5 years
Congrats to Dr. @isabelfulcher for successfully defending her dissertation today. Thanks for setting the pace in the relationship #PhD #stayinschool #harvardbutchill
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@CalebLareau
Caleb Lareau
3 years
All code and data has been made public to reproduce these results-- find them here: and here: . Also, check out TEA-seq, which similarly utilizes the Multiome kit for 3 modality detection !
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@CalebLareau
Caleb Lareau
11 months
The opportunity to join the world-class science and phenomenal collaborators at @MSKCancerCenter is incredibly special. I am so grateful to find my academic home in csBio, a community of many of the individuals in science that I admire and respect most, led by @dana_peer . 3/
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@CalebLareau
Caleb Lareau
4 years
This throws the door wide-open to ask integrative analyses of cell state and clonal cell lineage in human cells without the need to engineer genetic barcodes. For example, we observed clonal bias in an in vitro system of monocyte/erythroid differentiation 3/n
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@CalebLareau
Caleb Lareau
3 years
Finally, I want to clarify that I really would love for a method to come along and outperform mgatk. I'm not invested in the method being the best-- I'm interested in *us* using the best tools to understand human tissue physiology via mtDNA tracing 23/n
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@CalebLareau
Caleb Lareau
11 months
The theme of our lab’s research is Computational and Translational Immunology, which is purposefully broad but encompasses our goals of generating and using large-scale genomics data for translational impact. As an example, check out some recent work: . 2/
@CalebLareau
Caleb Lareau
11 months
Out today in @NatureGenet , our work utilizing single-cell multi-omics to define specific immune cell subsets that experience purifying selection against pathogenic mitochondrial DNA. Check out a thread about this work below: 1/22
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@CalebLareau
Caleb Lareau
1 year
What's fascinating is ... a completely different TCR takes over around round 18. Then between 18 and 30, we see the final TCR (that's likely linked to the clonal mtDNA variant) that persists through the rest of the experiment-- these waves of clonal succession are super cool...
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@CalebLareau
Caleb Lareau
2 years
@z_chiang @_bakshay you already know
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@CalebLareau
Caleb Lareau
6 years
Thanks to @github for renewing my student developer plan (free private repositories for 2 years!) Amazing service-- you guys are the best!
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@CalebLareau
Caleb Lareau
5 years
Thanks @aayushraman @tangming2005 . Here's a few thoughts on how I see the landscape of tools (thread) 1/n
@tangming2005
Ming "Tommy" Tang
5 years
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@CalebLareau
Caleb Lareau
6 years
Great talk from @JD_Buenrostro at @OMRF on our ongoing and new work in single cell epigenomics!
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@CalebLareau
Caleb Lareau
1 year
Best of all-- who is this carrier of a 1-in-a-billion mosaic variant you ask? 👀 Well, now you know 21/20
@Satpathology
Ansu Satpathy
1 year
Look what @CalebLareau found in my blood! 🧐
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@CalebLareau
Caleb Lareau
2 years
From qPCR , we observed HHV-6 reactivation and replication, observing DNA that increased over time in vitro. From this, we wondered what were the cell states underlying this reactivation? We proposed two possible models: 8/n
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@CalebLareau
Caleb Lareau
1 year
This variant is conserved with the human rCRS variant m.14795T>C, which has never been observed in the germline of any of the ~300,000 individuals recorded in mitomap but is a VUS in clinVAR . 3/n
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@CalebLareau
Caleb Lareau
4 years
As a teaching fellow for @XShirleyLiu 's computational biology and #bioinformatics class, we are trying to make a new homework question this year related to #COVID19 . I thinking of something related to sequence analysis with phylogenetics, but any other ideas would be welcomed!
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@CalebLareau
Caleb Lareau
3 years
If you compare/contrast the title of our @NatureBiotech version to the @biorxivpreprint version, you'll notice the addition of transcriptome! In a revision experiment, we introduce DOGMA-seq-- an assay that enables detection of DNA, RNA, and protein, spanning the central dogma!
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@CalebLareau
Caleb Lareau
2 years
Please have a look and let us know what you think! 19/n
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@CalebLareau
Caleb Lareau
2 years
10/10 paper and 15/10 tweet thread pun. A huge moment in the (prime-editing) revolution! Congrats @grunewaju and @JoungLab team!
@grunewaju
Julian Grünewald
2 years
Boston RT party!🧬So excited about our #CRISPR prime editing work, out @NatureBiotech today – great @JoungLab team work w/ Bret Miller, @ReganSzalay , @johnASeed1 , Chris Woodilla, @elizajaneholtz , @Karl_Petri & @JKeithJoung
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@CalebLareau
Caleb Lareau
2 years
This work was a massive team effort across several institutes in the US and internationally. I’m particularly grateful for my funding from @StanfordFellows , @StanfordPath , and @Parkerici that enabled me to pursue this fascinating research question 17/n.
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@CalebLareau
Caleb Lareau
8 months
Phenomenal new study from an incredibly talented team— a master class of mechanistic viral discovery from the @M_Munschauer group
@M_Munschauer
Mathias Munschauer
8 months
Paper alert 🚨 Thrilled to share the latest work from my group revealing how a host RNA-binding protein orchestrates SARS-CoV-2 RNA synthesis in human cells. Out in @CellCellPress today:
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@CalebLareau
Caleb Lareau
5 years
@LeifLudwig @julirsch Next, we wondered if these mutations were observed in human tissue. To look at this, we yolo realigned 424.4 billion reads from the GTEx project--turns out there are thousands of tissue-specific mtDNA mutations that we could detect! 9/n
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@CalebLareau
Caleb Lareau
5 years
Now, if you're convinced bap works as advertised, then we estimate how often barcode multiplets occur in single-cell data. Here, we do a deep dive into a public pbmc-5k dataset and estimate that 17.6% of barcodes may be included in multiplets... kinda crazy right? 18/n
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@CalebLareau
Caleb Lareau
1 year
PS- This analysis was enabled by the TRUST4 tool from @mourisl and @XShirleyLiu .
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@CalebLareau
Caleb Lareau
5 years
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@CalebLareau
Caleb Lareau
1 year
Finally, using a complementary approach (MAESTER, from @TylerEMiller and @vangalenlab ), @sydshaffer and colleagues tracked the clonal evolution of Barrett’s esophagus from origins of metaplasia to cancer. Super cool science here! 10/
@sydshaffer
Sydney Shaffer
1 year
Excited to share our latest preprint led by Rodrigo Gier!!🥳🥳 with @HuerosRaul and amazing collaborators @NancyZh60672287 @DrGaryFalk @LabMuir @tkarakasheva Lineage tracing with scRNA-seq to track the origins of metaplasia and its evolution to cancer.
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@CalebLareau
Caleb Lareau
1 year
ps how do I get a shirt
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@CalebLareau
Caleb Lareau
2 years
When we extended the culture, we observed evidence of lysis and infecting other cells in culture– causing the infection to quickly spread and infect many other cells in vitro. 11/n
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@CalebLareau
Caleb Lareau
6 years
High resolution discovery of chromatin interactions
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@CalebLareau
Caleb Lareau
2 years
We identified two such patients with HHV-6B super expressors in vivo and tracked patient phenotypes alongside scRNA-seq profiling. In both patients, the HHV-6 cells resolved within 1-2 weeks of detection. In one patient, Foscarnet may have contributed to rapid clearance. 13/n
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@CalebLareau
Caleb Lareau
2 years
First, viral reactivation could occur ~uniformly across cells in culture (Model 1). Alternatively, viral reactivation could be a rare phenomenon (Model 2). Using single-cell sequencing, we could discriminate between these two possibilities. 9/n
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@CalebLareau
Caleb Lareau
6 years
Running > 12,000 jobs on @BroadFireCloud has me like
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@CalebLareau
Caleb Lareau
4 years
What kind of satire is this @nbcsnl ?
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