Metabolic Systems Lab

The challenge

Metabolism is an integrated network of biochemical reactions that is essential for the proper functioning of living cells and, ultimately, of the human body as a whole. Disease-associated metabolic alterations, such as those occurring in cancer, reshape the cellular microenvironment by depleting essential nutrients and accumulating metabolic waste products, thereby promoting disease progression. By harnessing the tools of synthetic biology, metabolic engineering, and biomaterials science, we aim to reprogram the metabolic landscape of the cellular microenvironment to unlock new therapeutic opportunities.

Main Research Areas

Reprogramming tumor metabolism via cell-free antimetabolite synthesis

The accumulation of tumor-derived metabolites with immunosuppressive properties in the tumor microenvironment is increasingly recognized as a central feature of tumor progression. Metabolites such as lactate and succinate actively shape immune cell function, fostering an immunosuppressive environment that enables immune escape. Drawing on the principles of bottom-up synthetic metabolism, we engineer cell-free metabolic pathways that convert immunosuppressive metabolites into antimetabolites that selectively disrupt tumor metabolism. By coupling the consumption of immunosuppressive metabolites with the synthesis of therapeutic antimetabolites, this strategy exploits a defining feature of tumor metabolism to poison tumor cells using their own metabolic activity.

Engineering metabolically active biomaterials to reprogram the tumor microenvironment

The high metabolic demands of cancer cells drive the depletion of essential metabolites from the tumor microenvironment, as malignant cells compete for these molecules to sustain their growth and survival. The resulting metabolic imbalance impairs immune cell function, thereby promoting immune evasion. Recent studies have shown that the local replenishment of specific metabolites within tumors can restore immune cell function and enhance antitumor immunity. Building on this concept, we aim to engineer metabolically active biomaterials that function as “autonomous” systems programmed to sense local metabolic cues (sense), enzymatically synthesize target metabolites from locally available substrates (compute), and release the synthesized metabolites directly into the surrounding microenvironment (react). While our current focus is the tumor microenvironment, this strategy establishes a general framework for developing programmable biomaterials capable of reshaping the metabolic landscape of a broad range of disease-associated microenvironments.