With mixed emotions, we said farewell to our @jax.org summer student Eva Rios. She was a JOY to have in the lab - thoughtful, engaged, creative, a dot-connector and with a great sense of humor and desire to learn and be challenged 🤩 #SSP26 #JAXGenomicEducation #JAXresearch #JAXstemcellsdev

Clearing senescent MSCs at the CH stage delayed progression to AML and extended survival. Targeting the niche, not just the mutant cells themselves, slowed malignant evolution.

Correlation isn't causation, so we tested it 3 independent ways: genetic depletion of p16-hi cells (p16-3MR mice), the BCL2/BCLxL-targeted ABT-263, and senolytics dasatinib + quercetin. All three depleted senescent MSCs and shrank Dnmt3a-mutant chimerism in vivo.

Mechanism: Dnmt3a-mutant HSPCs secrete TNFα and IL-6 that selectively activate Stat3 and ROS in MSCs, driving p53/p21-dependent senescence. Blocking TNFα, IL-6, or Stat3 each prevented it.

uried in Fig. 2 but important: transplant conditioning (irradiation/busulfan) can be a confound. Using non-conditioned transplants, we show mutant clones still gain a fitness edge with natural aging, the first demonstration that Dnmt3a-mutant clones can do this.

MSCs from Dnmt3a-mutant mice show upregulated p53 targets, ROS, SASP, and senescence signatures, and the same signal shows up in human bone marrow MSCs from CHIP carriers across 4 different driver mutations (DNMT3A, TET2, ASXL1, CCAR1).

We ran scRNA-seq across non-hematopoietic bone marrow populations (MSCs, osteoblasts, endothelial cells) in mice with Dnmt3a-mutant vs. control hematopoiesis. One population stood out: mesenchymal stromal cells (MSCs) had the most changes, dominated by a senescence signature.

A huge congratulations to the newest graduate of the Trowbridge lab at The Jackson Laboratory @jax.org, Dr. Shawn David!! Shawn did a fantastic job defending his thesis today. So proud! 🎉 👏 🎊 #JAXGenomicEducation #UMaineGSBSE #JAXresearch #JAXstemcellsdev

1/3 Delighted to have visited the University of Pennsylvania this week, hosted by the fantastic Dr. Bobby Bowman who has built an exciting research program on the origins of myeloid malignancies and leukemia relapse.

With gratitude to the dynamic Dr. Naveen Pemmaraju for the invitation and opportunity to share our data and discoveries with clinicians and scientists at University of Texas MD Anderson Cancer Center! It was a thought-provoking and fun Q&A discussion.

⏲️The clock is ticking.. submit your abstract to the @isehsociety.bsky.social annual meeting by April 17th. Join us and be (re-)introduced to this awesome group of leading hematologists/stem cell biologists in a close-knit environment where you will receive in depth feedback on your work! #ISEH2026

Fun lab lunch & farewell to postdoc Jayna Mistry as she leaves us to start her own lab at University of East Anglia!! 🎉 Watch this space - Jayna is a creative and passionate scientist, can't wait to hear about her lab's big discoveries 🤩

We find that MitoQ also targets elevated mitochondrial respiration and the selective advantage of human DNMT3A-mutant HSCs, supporting species conservation.

Exploiting elevated mitochondrial membrane potential, we used long-chain alkyl-TPP molecules (ex. MitoQ) that selectively accumulate in the mitochondria. These caused reduced mitochondrial respiration, apoptosis, and ablated the competitive advantage of Dnmt3a-mutant HSCs.

Dnmt3a-mutant HSCs have DNA hypomethylation and increased expression of oxidative phosphorylation gene signatures, increased functional OXPHOS capacity, high mitochondrial membrane potential & greater dependence on mitochondrial respiration versus wild-type HSCs.

Using a mouse model of Dnmt3a-mutant CH that our lab previously developed, we found that mutant HSCs sustain elevated mitochondrial respiration which is associated with their resistance to aging-induced changes in the bone marrow microenvironment.

Happy holidays from the Trowbridge lab! The festive games got a wee bit competitive this year 😅 Thanks James for the inspiration!

Lastly, a shout out to my co-chair Sant-Rayn Pasricha (whom I will nudge onto Bluesky!) for a lot of laughs, for keeping an at-times challenging job light and fun, & for literally sharing the spotlight with me. Wouldn't have wanted to partner with anyone else. Hope to see everyone at #ASH25!

#ASH24 badge has arrived ✅ Sant-Rayn Pasricha & I are delighted & excited to see everyone in San Diego. Getting ready for Best of ASH! During the meeting, stay tuned for posts about sessions you do not want to miss. 😎