Assistant Professor @UPenn | Study epigenetics, gene regulation and cancer | views my own
Philadelphia
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Departmental trainee seminar kickoff + Outstanding Publication Awards! Congrats to postdoc winner Diqiu (@junwei_s lab), and graduate student winner Krista from my lab! Read Krista’s paper on RNA-reinforced condensate nucleation cell.com/molecular-cell/full… @Penn_CBIO
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Good news from lab: Congrats to Steph on a T32 award; Qinglan on a Marlene Shlomchik Fellowship in Cancer Research; Amba & Amanda did an excellent job presenting posters for summer projects; and Krista on defending her thesis and becoming our first Ph.D. graduate! 🎉 #PoundPI
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Four inspiring days at the FASAB Biological Acetylation in Health and Disease Conference in Porto. Great science, stimulating discussions, and wonderful interactions with many colleagues, old and new. Looking forward to seeing everyone again in 2028! #BAHSRC
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Excited to share that our preprint 'RNA reinforces condensate nucleation on chromatin to amplify oncogenic transcription' is now online @MolecularCell cell.com/molecular-cell/full… @PennMedCSO @PennCancer @PennEpiInst
(1/n) Excited to share our new preprint! We uncover that RNA actively promotes nucleation and function of pathogenic condensates, amplifying locus-specific oncogenic transcription and promoting tumorigenesis. #epigenetics #condensates #cancer #RNA biorxiv.org/content/10.1101/…
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Join us Aug 3–6 in Porto for the #FASEB Biological Acetylation Conference! great lineup spanning #chromatin #epigenetics #metabolism #cancer and drug development! keynotes by Asifa Akhtar and Shelley Berger! #BAHSRC2026 events.faseb.org/event/biolo…
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Heading to San Diego for #AACR26! excited to present our latest work on condensates at the Major Symposium on chromatin, epigenetics, and cancer, alongside leaders in the field @TheRobertsLab1 @Armstrong_dfci. Come join the discussion if you’re interested! @PennMedicine
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A short but wonderful visit at UCSF - thanks to Xiaokun @ShuLab2010 and Danica for the invitation to share our work on #epigenetics #condensates #cancer and to friends (old and new) for the great discussion! And so glad I made it home before the snowstorm shut everything down
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(7/n) We propose that pathogenic condensates exploit RNA to reinforce locus-specific nucleation and amplify transcriptional programs that drive disease. This may set them apart from normal condensates which may be more sensitive to RNA-mediated negative feedback.
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(6/n) Does this matter functionally? In leukemogenesis models, ENLmut deficient in RNA binding fail to form condensate at and activate key oncogenic targets and cannot initiate leukemia in mice.
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(5/n) Notably, RNA binding preferentially enhances ENL occupancy and transcriptional bursting at top-bound, condensate-permissive loci without affecting general chromatin binding property, thus amplifying locus-specific gene expression.
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(4/n) Using a chemically inducible displacement + wash-off system, we visualize and quantitatively show that efficient re-nucleation of ENL condensates at the endogenous target HOXA requires both transcription (RNA synthesis) and RNA binding.
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(3/n) We now show that ENL binds RNA via its YEATS domain. This interaction enhances condensate formation in vitro and across diverse cell types. Specifically disrupting RNA binding reduces ENLmut condensate formation and chromatin engagement at highly selective genomic targets.
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Thrilled to receive the Tony Hunter Award (Junior Investigator) from the Association of Chinese Americans in Cancer Research and to present our work alongside senior awardee Dr. Chuan He. Proud to be part of this amazing community! #immigrant #CancerResearch @PennMedCSO
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Had a great time visiting Dana-Farber Cancer Institute and sharing our work on chromatin mechanisms in cancer! Huge thanks to @JunQiLab for the invitation and generous hosting. So much fun reconnecting with mentor & old friends, making new ones, & a full day of amazing science!
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Having a wonderful time at #acetylation #epigenetics FASEB conference! It started with a tribute to the pioneer of the field, David Allis, followed by diverse topics, great science, and lots of fun interactions in the historic city #Rome #BAHSRC
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annual departmental @Penn_CBIO retreat at #skytop beautiful place, great science, and lots of interactions and fun! And, our amazing sophomore Michele found out her acceptance into Flexmed program @MountSinaiNYC medical school!
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bittersweet moment as we send off our absolutely amazing technician, Sylvia, to MD/PhD #WashU and high school student, Samantha, to college @Cornell I chose the book by @kkariko hoping it inspires them to continue breaking through the next chapter of life #proudPI #womeninstem
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Interested in transcriptional condensates and their dysregulation in diseases? Check out our mini-review on recent advances in mechanisms, biological functions, and open questions in this area, led by @kaeli_mathias and Yiman Liu. free access authors.elsevier.com/a/1j8Sx…
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A great pleasure hosting @ChrisVakoc for distinguished cancer series at @PennMedicine . Thank you for sharing exciting discoveries on #transcription #signaling vulnerabilities in human #cancer stemming from elegant CRISPR screens! @ChrisVakoc Gerd Blobel @junwei_s @AsanganiLab
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(9/n) Remarkably, transient treatment of embryos with this inhibitor largely rescues mutant ENL-induced developmental and transcriptomic defects.
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(7/n) In addition to nephron progenitors, we show that mutant ENL alters the open chromatin landscape of Foxd1+ stromal progenitors, which might affect stroma-nephron interactions by aberrantly activating paracrine Wnt signaling.
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(6/n) scRNA-seq and snATAC-seq reveal ENLmut promotes commitment of nephron progenitors while simultaneously restricting their differentiation through misregulation of TF regulons (e.g. HOX). It also induces abnormal progenitor cells that lose kidney chromatin identity
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(5/n) Using single-cell RNA-seq, we reveal that mutant ENL alters cellular composition and differentiation trajectories in embryonic kidneys, inducing transcriptomic changes involved in both self-renewal and cell fate commitment in nephron progenitors.
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(4/n) By creating a conditional knock-in mouse model, we show that heterozygous expression of mutant ENL during kidney development disrupts embryonic kidney differentiation, leading to kidney dysfunction and early postnatal mortality in mice.
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(1/n) preprint on how Wilms tumor mutations perturb kidney development and how to target this by small molecule! led by Lele Song and Qinglan Li and wonderful collaborators @KSusztak @hao_wu_7 @sasaki_kotaro with input from @KaiTanLab1 @DengYanxiang biorxiv.org/content/10.1101/…
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(8/n) A big shout out to postdocs Yiman Liu and Qinglan Li, my lab, and our collaborators @PennMedicine. Many thanks to our editor @CD_AACR and reviewers for a rigorous and speedy review process. Thanks for funding from @LLSResearch @AmericanCancer @NIH_CommonFund @pewtrusts
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(6/n) can we target these oncogenic condensates? we show that an acetyl-binding inhibitor of mutant ENL can displace these condensates from target loci, inhibit mutant ENL-induced chromatin changes, and delay AML initiation and progression in animal models.
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(5/n) Using DNA FISH coupled with IF, we show that Mutant ENL forms condensates in hematopoietic stem/progenitor cells at key leukemogenic genes (e.g. HOXA and Meis1); importantly, disrupting condensate formation via mutagenesis impairs ENLmut chromatin and oncogenic function.
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(4/n) Mutant ENL alters developmental and inflammatory gene programs in part by regulating histone modification, promoting p300-K27ac axis, thereby locking key oncogenic loci (e.g. HOXA and Meis1) in a constant ‘on’ state.
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(3/n) By creating a conditional knock-in mouse model, we show that heterozygous mutant ENL perturbs normal hematopoiesis, induces aberrant expansion of myeloid progenitors, and triggers rapid AML onset in mice as a single hit.
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The lab went out for a Hotpot lunch to celebrate recent fellowships/awards to @kaeli_mathias @kristaa122995 Yiman Liu; welcome our newest @CAMBUpenn Ph.D. student Arushi Sahay; and send off high school student Samantha Bramen. hope all enjoy the summer before it ends soon!
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Congrats to our own @ChujieGong @CAMBUpenn on passing prelim exam with flying colors and becoming a PhD candidate! looking forward to what he will accomplish in the next few years! #proudPI
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Congrats to our undergrad Sylvia on graduating from Penn Vagelos Program plus winning a highly competitive Rose award (10/year across penn) for her outstanding thesis research. Can’t wait to see what she will accomplish next! #proudPI #WomenInSTEM
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Honored to be invited by trainees to present at the Salk T32 cancer symposium today. A full day of great science and fun interactions with trainees and colleagues! + beautiful weather and sunset. @salkinstitute
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Ending a busy but productive and fun 2022 with lab holiday party and secret Santa. We celebrate all personal/lab milestones: engagement, passing qualify, first papers, fellowships, lab 8K run, graduation, new job, and more. Happy holidays to all and Look forward to a great 2023!
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Thanks to @bsabari for writing a thoughtful preview on our @MolecularCell study on pathogenic transcriptional condensates. cell.com/molecular-cell/full… And check out our fun #halloween theme cover image illustrating context-dependent condensate properties/function.
Check out the preview that @mikayla_eppert and I wrote on a new study from @LilingWanLab and Haitao Li. Also, congrats to them on getting the cover.
50 day free link: authors.elsevier.com/a/1g115…
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Lab fun in the past few days!! (1) a group hike to enjoy fall scenery before it ends; (2) lunch celebrating new paper (3) Halloween dress-up followed by fun science discussion (4) special congrats to Lele Song, first lab member who had her paper out last week.
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lab and personal milestones! Pic 1&2: celebrate first paper from the lab @CD_AACR with @kathrinbernt, congrats to all involved and such great teamwork during pandemic. Pic 3&4 : personal side, congrats to our newly engaged @kristaa122995 &Kyle; Chujie&Ghita! #happylife #proudPI
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(6/n) ENL YEATS inhibition impairs the clonogenic potential and induces differentiation of MLL-r and NPM1-mutated primary AML patient samples as well as blocks disease progression in vivo without causing overt toxicity
(5/n) we delineated rapid chromatin and transcriptional changes upon ENL inhibitor treatment (e.g. 30 min) and revealed a direct function of the YEATS – acetylation interaction on chromatin and transcription elongation
(5/n) we delineated rapid chromatin and transcriptional changes upon ENL inhibitor treatment (e.g. 30 min) and revealed a direct function of the YEATS – acetylation interaction on chromatin and transcription elongation
(4/n) cell lines and primary AML samples carrying MLL rearrangements or NPM1 mutations are responsive to ENL inhibitor. a CRISPR/Cas9 mutagenesis screen uncovered an ENL mutation that confers resistance to the inhibitor, providing 'genetic proof' for on-target activity
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(4/n) cell lines and primary AML samples carrying MLL rearrangements or NPM1 mutations are responsive to ENL inhibitor. a CRISPR/Cas9 mutagenesis screen uncovered an ENL mutation that confers resistance to the inhibitor, providing 'genetic proof' for on-target activity
(3/n) considering the lack of in vivo bioavailable ENL inhibitor, we developed TDI-11055 through structure-based optimization of a previously reported probe (SGC-iMLLT) to enable its use for cancer studies.
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(3/n) considering the lack of in vivo bioavailable ENL inhibitor, we developed TDI-11055 through structure-based optimization of a previously reported probe (SGC-iMLLT) to enable its use for cancer studies.
(2/n) we and others previously identified ENL as histone acetylation reader via its YEATS domain and showed that this reading activity is critical for maintenance of subsets of AML. These results motivated development of ENL YEATS inhibitors. pubmed.ncbi.nlm.nih.gov/2824…
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congratulations to @kristaa122995 for becoming a Ph.D. candidate! so proud of you and can't wait to see the great things you will achieve next! @PennCBP @CAMBUpenn @Penn_CBIO #ProudPI
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Congratulations to @kaeli_mathias (co-mentored w/ @MustafaMir16) for passing her prelim @BMBGGUPENN and becoming the first Ph.D. candidate in the lab! so proud of you and can't wait to see great things you will accomplish in the next few years! #ProudPI #WomenInSTEM
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welcome new lab members! Excited that @kristaa122995 from @CAMBUpenn and @kaeli_mathias from @BMBGGUPENN (co-mentored w/ @MustafaMir16) joined for their Ph.D; Sylvia #PennVagelos for undergrad research; and Chujie @CAMBUpenn for his first rotation. We have a great team!
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just realized our profile pic with heart-shape kidney tubule staining is a perfect gift for today #academicvalentine
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two fantastic meetings at the same time #Kscancerepigenetics #KSgene! why wait? still time to register
There's still time to register and present a poster at #KSgene! @berger_lab @LilingWanLab @bfariabi all giving talks! @KeystoneSymp
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