Tumorigenesis in the Metabolically Aged Tissue Microenvironment
Aging reshapes the ecology of tissues. With time, the microenvironment no longer provides an even playing field: resources such as iron and other metabolites become scarce, immune cells lose their supply chains, and precancerous clones adapt to survive where normal cells cannot. These metabolic bottlenecks create ecological pressures that shift the balance from healthy tissue renewal toward cancer initiation and progression.
Our lab investigates how aging and prior cancer therapy — the two strongest predictors of cancer — converge on this problem. By mapping which metabolites become limiting in aged or therapy-altered tissues, and by uncovering how these scarcities influence clonal selection and immune surveillance, we aim to identify actionable bottlenecks. The ultimate goal: reprogram the aged microenvironment to delay cancer initiation, boost immunity, and open new paths for prevention and treatment.
Research projects
Colon metabolism and cancer promotion
How aging reshapes colon ecology to promote cancer?
Colorectal cancer remains one of the most common and deadly malignancies worldwide. We ask how aging processes in the colon microenvironment create metabolic bottlenecks that alter the balance between healthy epithelium and precancerous clones. Our preliminary findings suggest that iron homeostasis becomes disrupted with aging, creating an environment where precancerous cells gain a competitive advantage over normal tissue. We hypothesize that these ecological pressures accelerate tumorigenesis by shifting the fitness landscape of the colon. By identifying the key mechanisms and biomarkers of age-associated metabolic scarcities, we aim to open new avenues for prevention, early detection, and therapeutic intervention in colorectal cancer.
In the lab: Marc Guasch Piqueras, PhD student, leads this project.
Bone marrow metabolism and cancer promotion
How aging and therapy reshape bone marrow ecology to drive clonal evolution?
Myelodysplastic syndrome (MDS) is a clonal hematopoietic disorder with high risk of progression to acute myeloid leukemia (AML). Older age and prior chemotherapy are major risk factors — both act as ecological stressors that reshape the bone marrow microenvironment. We hypothesize that aging- and therapy-induced metabolic bottlenecks suppress normal blood cell renewal while favoring the expansion of precancerous clones. In this project, we investigate how these bottlenecks alter clonal diversity and immune balance, and whether restoring healthy metabolic supply chains can delay or prevent malignant progression.
In the lab: Ning Huang, PhD student, leads this project.
