bizarMD
@BizarMd
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Medical oncologist studying the intersection of cancer genomics, immunology and metastasis. https://t.co/uP5TGrYD7Z
New York, NY
Joined October 2018
It was an incredible honor to be hosted at @StanfordMed for the @StanfordPath annual retreat as the inaugural recipient of the national Galli Prize in Pathology! Endless thanks to @BizarMd for his mentorship and to the whole Izar lab family
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Now also with a beautiful preview of the work by @SanchoShimizu
https://t.co/twRzUNaiUx
cell.com
Saturation genome editing meets functional phenotyping to turn sequencing ambiguity into actionable diagnoses.
Our newest work from @BizarMd lab is now in print at @CellCellPress! Check out our tweetorial below to learn more about our work establishing a scalable variant classification appraoch for inborn errors of immunity, which has already directly enabled the treatment of a patient!
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Grateful for many outstanding collaborators in many departments/centers @columbiacancer @Columbia @ColumbiaMed @ColumbiaSurgery @ColumbiaBME and of course supporters of our lab @NIH @theNCI @PershingSqFdn @CancerResearch @vFound @MelanomaReAlli
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Our data also suggest that subsequent metastatic behavior may be determined early in tumorigenesis and partly influenced by microenvironmental cues. More work on this intriguing concept forthcoming!...
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Working with long-term collaborator @elhamazizi, we used Echidna ( https://t.co/nXz42TJ4jF) to measure whether these changes were determined by differences in gene dosage - they were not! And there were no other genomic events explaining this observation.
biorxiv.org
Phenotypic plasticity, the ability of cells to adapt their behavior in response to genetic or environmental changes, is a fundamental biological process that drives cellular diversity in both normal...
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Cancer cell states in primary tumors strongly correlated with that of transcriptional profiles of their ultimate target organ, suggesting that pre-existing states dictate metastatic organotropism. Conceptually similar to what we & others are seeing in other metastatic niches
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We (Mori @MichaelMayMD @DrGManji ) find that in patients with resected pancreatic cancer isolated metastatic recurrence in the liver do worse than those with lung recurrence. We profiled (snRNA+lpWGS) their primaries & made an intriguing observation:
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Really important study that extends principles of cancer neuroscience of primary brain tumors to that of brain metastasis (in this case, in small cell lung cancer). Congrats @humsav!!
1/ Very happy to share our first publication out of the lab highlighting the role of neural activity in SCLC progression in collaboration with @michelle_monje and led by @SavchukSol and Kaylee Gentry @BWHNeurology @MGBResearchNews #CancerNeuroscience 🧵… https://t.co/RcwHClSONH
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Brilliant work. Necrosis is no longer just a non-specific process but active and NET pro-metastatic…
Proud to share @niseto’s (new PI @TheCrick) paper: As a postdoc (@CSHL/@HopkinsMedicine), he found #NETs in necrotic tumors—I shrugged. But he looked closer: NETs block tumor vessel perfusion, causing necrosis, hypoxia, EMT & #Metastasis. https://t.co/gsaUTA1dfw
@JHU_BDP @Nature
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For this week’s #MRFResearchWednesday, we’re spotlighting 2025 Medical Student Grant Awardee @Zwalsh96 of @ColumbiaMed, working in the Izar Lab, with @BizarMd. His project, “Leveraging T Cell Genetic Variants to Enhance Melanoma Immunotherapies,” explores new ways to improve
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Now online! Scalable generation and functional classification of genetic variants in inborn errors of immunity to accelerate clinical diagnosis and treatment
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Thrilled to share the latest work from my PhD in the @BizarMd group! This has been a dream MD/PhD project, culminating in data that has already enabled access to precision therapy for a patient. Tweetorial below:
Excited to share a new paper: https://t.co/087iX9SkJd
@CellCellPress: a framework to accelerate variant classification, diagnosis & treatment of immune disorders & genetic disorders more broadly. Led by superstar, juggernaut & future dermatologist @zwalsh96
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I am extremely grateful for support from @columbiacancer Human Tissue Immunology and Immunotherapy Initiative (HTI3) @PharmingGroupNV @NIH @NCICancerCtrl @CancerResearch
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This was a big team effort with many folks from my lab @FrangiehChris @NeehaKothapalli @JCA_Melms Clarissa Heck & many more. Grateful for a fantastic collaboration with disease experts @joshuamilner2 @123456789Dusan
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This work has already impacted care: a patient was treated with leniolisib based directly on our variant classification. And it serves as a useful blueprint for other IEIs and beyond ... Stay tuned!
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How relevant are these variants? By integrating our screen with All of Us (>600K genomes) and an IEI cohort (>8K pts), we found 100+ carriers enriched for immune disease phenotypes. So the disease could be magnitudes of order more common than we thought...
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Some PIK3R1 variants were only partially responsive to leniolisib. We uncovered combo therapies (e.g. leniolisib + mTORi) that restored suppression in both edited cells and patient samples.
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We validated screen results and phenotypes using T cells from two APDS patients with variants mapping to structural GOF hotspots flagged by our screen, directly linking screen data to real disease.
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T cells with newly identified GOF variants showed hyperactivation, exhaustion & transcriptional changes—mirroring APDS patient cells. Like patients, they also responded to leniolisib.
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The result: reliable recovery of known pathogenic variants, along with dozens of novel GOF variants previously unstudied or classified as VUS
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