Research
Cancer cachexia is not the failure of a single tissue. It emerges from a network of signals and metabolic changes that connects a tumor with organs throughout the body. We study that network from organism-wide discovery to causal mechanism and preclinical intervention.
Systems-level discovery
Cancer cachexia is a systemic, multi-organ syndrome. Studies centered on a single organ can reveal local pathology, but they may miss the circulating signals, tissue responses, and metabolic exchanges that coordinate disease across the body.
We use whole-body single-nucleus RNA sequencing to capture cell states across many tissues in the same organism. In a Drosophila model of cancer cachexia, this approach produced an organism-wide view of disease progression and revealed conserved programs that can be tested in mouse models and human datasets.
Signals and metabolism
Tumors can behave like dysregulated signaling organs, releasing cytokines and other factors that alter distant tissues. We integrate transcriptomics with metabolomics and lipidomics to connect these inter-organ signals with their metabolic consequences.
We develop computational tools, including FlyPhoneDB2, to analyze whole-body single-nucleus RNA-sequencing datasets and reconstruct cell–cell communication across tissues. Complementary metabolic inference helps us determine how these signals redirect pathways across the liver-like fat body, renal tissues, adipose stores, nervous system, and other organs.
Translational discovery cycle
Our laboratory builds a bidirectional patient-to-model-to-patient discovery pipeline. Recurrent cancer-associated mutations and clinical datasets guide rapid Drosophila modeling to uncover early drivers of organ dysfunction, systemic signaling, and cachexia.
Conserved pathways and metabolic circuits identified in Drosophila are then tested in mouse models and evaluated in clinical datasets. This cross-species framework keeps mechanistic discovery anchored in human disease while helping prioritize candidate therapeutic targets for preclinical validation.
From maps to causality
By combining functional genetics with evidence across fly, mouse, and human systems, we prioritize conserved mechanisms with the strongest potential to become candidate therapeutic targets and preclinical intervention strategies.
Tumor-derived cytokine signaling activates an IL-6/JAK-STAT program that increases hepatic gluconeogenesis. Work across flies and mice identified PDK3 as a conserved node associated with disrupted amino-acid metabolism and systemic metabolic homeostasis.
Read the studyIL-6-driven lipid remodeling involving LPL and CERS5/6 promotes hepatic ceramide accumulation, with consequences for autophagy and organelle function. These pathways represent candidate intervention points that warrant further validation.
Read the preprintA Drosophila model revealed that the tumor-secreted ligand Pvf1 can act directly on renal cells, providing a genetically tractable system for studying paraneoplastic kidney dysfunction apart from the effects of cancer therapy.
Read the studyOur work examines how tumors co-opt host renal coenzyme A production to support proliferative metabolism. This organ-to-tumor exchange reveals potential metabolic vulnerabilities for further preclinical investigation.
Read the study