Excited to share our paper out today in @CellPressNews discovering RNA mis-splicing derived neoantigens & their cognate T cell receptors (TCRs) as well as characterization of endogenous neoantigen T cells in leukemia patients. https://t.co/hVucfdL0oZ

Our phase II trial of Ulixertinib in adults with histiocytosis is open and enrolling so please reach out with any referrals!!: https://t.co/7bTsy5l5ob

Importantly both mice and patients with class 3 MEK mutations respond to ERK inhibition with Ulixertinib. Through FDA compassionate use and help of @BioMedValley, we treated 5 MEK1 E102_I103del mutant patients with Ulixertinib and saw partial or complete responses:

We then created a conditional knockin mouse model of the most common MEK mutation – MEK1 E102_I103del and fund that these mice develop a high penetrance histiocytosis affecting the skin and hematopoietic organs:

Now across an international cohort of 498 patients we identify that RAF-independent MEK mutations (which are common amongst histiocytosis patients) are associated with progression to MEK inhibition:

Clinically led by Eli Diamond and former Abdel-Wahab lab member (now @RutgersCancer) Benjamin Durham + Takeshi Fujino. Prior work by our group led to FDA-approval of vemurafenib for BRAFV600E mutant histiocytosis followed by Cobimetinib for BRAF WT: https://t.co/iDY6seLEl2

Excited to announce a new publication from our @MSKCancerCenter Histiocytosis group identifying a predictor for impaired response to MEK inhibition in histiocytosis patients and the potential for ERK inhibition. Out today in @Cancer_Cell. https://t.co/ajXBBXm3eM

Congratulations to @DaniyanMd & team from @MSKCancerCenter on publication of the initial data from AML patients treated with IL-18 secreting CD371 CAR T cells @MSK. https://t.co/1Ai6kwl7HR 3 / 5 patients experienced MRD-negative morphologic leukemia free state.

If you’re interested in the interplay between regulation (or mis-regulation) of RNA processing and cancer, please check out the 2025 FASEB RNA Processing in Cancer meeting Oct 5-9 2025 in Sacramento CA! https://t.co/nF6SDK7vwB

Excited to share our new study, in close collaboration with @AbdelWahablab and @DaniyanMd led by the exceptionally talented scientists @PuZhang09980432 and @TomZhendong https://t.co/JLSNt1putl

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 https://t.co/bnQmzrEg6f @PennCancer @MSKCancerCenter

It turns out that ARHGAP45 also encodes the first identified minor histocompatibility antigen (HA-1) and we present a new cell therapeutic approach to target HA-1 and upregulate ARHGAP45 derived epitopes. Thanks to @LLSusa, @theNCI, @MSKCancerCenter for their support.

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: https://t.co/sxxdNVQyt1

Amazing speaker lineup with @SKousteni, @rosslevinemd, @The_Will_Lab, @GitlinLab_MSK, @TheDoctorIsVin, @zha_lab, @Amitvermamds, @Doulatov_lab, and others.

Excited to announce our annual New York City Edward P. Evans MDS Centers Symposium across @MSKCancerCenter & @Columbia on Monday, July 14, 2025. This year to be held at @MSKCancerCenter. See this flyer below and register here: https://t.co/uNeFLh0O2z

We are now excited to develop this approach for myeloid leukemia patients with mutations in splicing factors. Thank you to @break_cancer, @ASH_hematology, @LLSusa, @nih_nhlbi, @theNCI, @parkerici, and the Edward P. Evans MDS Foundation

Importantly we were able to identify neoantigen-specific CD8 T cells in patients with active MDS and AML. However, these neoantigen specific T cells had clear evidence of dysfunction, likely explaining the initiation/maintenance of these malignancies

We now find that MDS and AML patients with mutations in the splicing machinery create endogenous mis-splicing derived immunogenic peptides which are shared across patients (“public”) and can be used to isolate tumor-selective TCRs.

In 2021, @bradleybio and our lab identified that pharmacologic modulation of splicing creates bona fide RNA mis-splicing derived neoantigens which can augment immune checkpoint blockade efficacy in syngeneic solid tumor models:

Mutations in genes encoding RNA splicing factors occur in 50-80% of patients with myelodysplastic neoplasms and create stereotyped changes in RNA splicing consistent across patients.

@fredhutch.bsky.social and with amazing TCR expertise from @KlebanoffLab @mskcancercenter.bsky.social. Also wonderful help from Jeff Molldrem group @MDAndersonNews