Junwei Shi

Excited to share our new work on direct protein-based genome editing in primary cells. We termed it Peptide-Assisted Genome Editing (PAGE) CRISPR-Cas platform. This platform allows rapid and effective editing of primary cells with minimal toxicity. go.nature.com/3LB007T

Healthy blood cells can live without ARHGAP45—but acute myeloid leukemia cells can’t. 🩸 Junwei Shi, PhD, Associate Professor of Cancer Biology (@junwei_s) and team show a CAR T + CDC42 inhibition strategy could target AML with minimal side effects. bit.ly/45OyXQu

Systematic evaluation of GAPs and GEFs identifies a targetable dependency for hematopoietic malignancies ft. Yuqiao Liu & @junwei_s (@Penn_CBIO) @CD_AACR aacrjournals.org/cancerdiscover…

@AbdelWahablab @DaniyanMd @PuZhang09980432 @TomZhendong likewise

@junwei_s @DaniyanMd @PuZhang09980432 @TomZhendong It was really great finally to have a project to work with you on @junwei_s after all of years of friendship!

Excited to share our new study, in close collaboration with @AbdelWahablab and @DaniyanMd led by the exceptionally talented scientists @PuZhang09980432 and @TomZhendong doi.org/10.1158/2159-8…

@AbdelWahablab @DaniyanMd @PuZhang09980432 @TomZhendong This has truly been a fantastic collaboration that I can only dream of @AbdelWahablab, @DaniyanMd, @TomZhendong, and @PuZhang09980432

@AbdelWahablab @DaniyanMd @PuZhang09980432 @TomZhendong Even more exciting: CDC42 inhibition not only synergizes with ARHGAP45 loss intrinsically in leukemia cells, but also enhances TCR-CAR T cell function. A dual strategy to target cancer cells and augment immune responses.

@ElizSMcKenna @CD_AACR @PuZhang09980432 @TomZhendong @DaniyanMd @AbdelWahablab @PennCancer @MSKCancerCenter Many thanks for your guidance and support throughout the review process @ElizSMcKenna and @lisasitu

Now online in @CD_AACR: Systematic Evaluation of GAPs and GEFs Identifies a Targetable Dependency for Hematopoietic Malignancies - by @PuZhang09980432, @TomZhendong, @DaniyanMd, @AbdelWahablab, @junwei_s, and colleagues doi.org/10.1158/2159-8… @PennCancer @MSKCancerCenter

@AbdelWahablab @DaniyanMd @PuZhang09980432 @TomZhendong @ChrisVakoc This has truly been a fantastic collaboration that I can only dream of @AbdelWahablab, @DaniyanMd, @TomZhendong, and @PuZhang09980432

Excited to share that my first author paper entitled “Systematic evaluation of GAPs and GEFs identifies a targetable dependency for hematopoietic malignancies” is out on @CD_AACR. In the study, we used domain-focused CRISPR functional genomics and epistasis screen to systematically map GAPs and GEFs in cancer in vivo and in vitro, uncovering ARHGAP45 as a shared dependency across blood cancers but dispensable for normal blood cells. Highlights: 1)Using a modified sgRNA expression vector that permits dual genetic perturbation, we systematically perturbed 1,293 gene pairs by pairing ARHGAP45 with pooled sgRNA libraries against 173 GAPs, 103 GEFs, 170 GTPases, 246 glycosylation factors, and 601 kinases annotated in the human genome. 2)ARHGAP45 maintains leukemia stemness by regulating RhoA and CDC42 activity. We found that 'Goldilocks' effect of RhoA strikes a balance between a tumor suppressor and a tumor driver. 3)Our screens identified GMIP (also known as ARHGAP46) as a synergistic partner. GMIP, which clusters closely with ARHGAP45 in phylogenetic analyses, was shown to physically interact with ARHGAP45 by IP-MS analysis, suggesting that dual perturbation of these functionally redundant proteins may further impair leukemia cell growth. Unexpectedly, GTPases such as KRAS and CDC42, along with SOS1, the GEF of KRAS, showed synergistic genetic interactions with ARHGAP45, implying possible counteractive pathways of KRAS or CDC42 GTPase against RhoA. 4) We developed a novel and potent HA-1H–targeting single chain TCR T cells against ARHGAP45-derived minor histocompatibility antigen-presenting cancers. 5) CDC42 inhibition boosts HA-1H antigen presentation and ARHGAP45-targeted cell therapy for potent anti-leukemia effects in mice. Proud to see this work pave the way for precision immunotherapies in hematologic malignancies. Thanks to my postdoctoral mentor, @AbdelWahablab, for his great mentorship. The work was impossible without the guidance from @junwei_s, @TomZhendong, @DaniyanMd. Thanks to @Gravity_X_Pan for his expert analysis of patient single cell data.

Excited to announce a new paper in @CD_AACR with @junwei_s, @TomZhendong, @DaniyanMd and led by @PuZhang09980432. We perform screens of GAPs and GEFs in AML and discover a hematopoietic-specific GAP (ARHGAP45) required in AML: aacrjournals.org/cancerdiscover…

@MAF_Dawson Congrats!!! Well deserved

Incredibly humbled & grateful to @ASH_hematology for the honour of the William Dameshek Prize. A recognition that belongs to the awesome scientists I have the privilege of working with every day in @TheDawsonLab @PeterMacRes @GenCancerCentre

@EvanWeberPhD @Nature @alexdoan96 @kpmueller1 @andy_yhchen Congrats!!! This is amazing

Memory genes are enriched in CAR T cells that persist and control tumors in patients. But which transcription factors drive beneficial memory programs? We answer this in our lab’s first paper in @Nature led by @alexdoan96 @kpmueller1 @andy_yhchen. 1/ nature.com/articles/s4158…

@RogerRogergr @vidhya_k7 @RobertLDilley @FoglizzoMartina @zeqiraj congrats on another master piece!

We're excited to report a new mechanism of replisome proteostasis cell.com/cell/fulltext/…. 55LCC ATPase/unfoldase complex dependent replisome turnover prevents chromosome instability. Great collaboration by @vidhya_k7 and @RobertLDilley with @FoglizzoMartina and @zeqiraj.

The last lead author article from my PhD is out! In @NAR_open, we report our mechanistic study on how Cas9 and AID enzymes collaborate to shape base editing outcomes. Leveraging these insights, we create hyperactive BEs with the potential for targeted gene diversification. 1/

1/Excited to share my first author publication where we create split-engineered base editors (seBEs). Here, we place base editors under the control of a small-molecule to regulate the timing of genome editing and decrease off-target effects. To achieve it: nature.com/articles/s4158…