Grateful to @nature.com.web.brid.gy editors & reviewers for valuable guidance 🙏
Special thanks to our fantastic Starczynowski lab team👨‍🔬👩‍🔬
#Nature #CincyChildrens #CincyResearch #Aging #Leukemia #AML #MDS #ClonalHematopoiesis #hematopoiesis #Hematology #Oncology #GutHealth #microbiota #microbiome

How Bacteria in Our Aging Guts Can Elevate Risk of Leukemia and Perhaps More - Research Horizons

In summary, our findings open new avenues for preventing age-related blood cancers by modulating gut health or blocking the ADP-heptose–ALPK1 pathway. Stay tuned for more on this exciting frontier!!
scienceblog.cincinnatichildrens.org/how-bacteria...

To identify therapeutic target, we conducted parallel experiments involving inhibitor screen against all NF-kB effectors, and 🔥; UBE2N was the target!! Therefore, ADP-heptose-induced TIFAsomes and pre-leukemic cell growth was dependent on UBE2N!

Next, we determined the effect of ADP-heptose on pre-leukemic cells in vivo, and found it robustly expands both human & mouse pre-leukemic stem cells.

We dug deeper and focused on a sugar metabolite, ADP-heptose which is specifically secreted by gram negative bacteria, and triggers NF-kB via ALPK1 and TIFAsomes. Surprisingly, ADP-heptose was highly elevated in healthy aged, CHIP and MDS individuals; and correlated with age.

Aging often disrupts the gut permeability and lead to abundance of gram negative bacteria🦠. Using fecal microbiota transplantation and antibiotics🧪🧬, we found pre-leukemic stem cell expansion specifically required gram negative bacteria!

We set out to tackle the most loved and hot question in the field- what drives pre-leukemic cell expansion as we age? The answer may lie in our gut! By modeling CHIP using chimeric mice, we found gut injury (DSS) directly promotes pre-leukemic cell expansion and their function.

Big thanks🙏to my mentor, Daniel Starczynowski
for his unwavering guidance; and colleague, Avery Sampson for unlimited support; all our collaborators and funding agencies

Excited to share our latest research published today
@nature.com.web.brid.gy"Microbial metabolite drives aging-related clonal hematopoiesis via ALPK1"—study uncovering how diminished gut health and microbiome changes with age promote pre-leukemic cells & disease risk
www.nature.com/articles/s41...