Kynurenine as a metabolic biomarker in TSC

This seed-funded project from the national Tuberous Sclerosis Association will investigate metabolic biomarkers for tuberous sclerosis complex (TSC). Building on his expertise in cellular metabolism and disease signaling pathways, the researchers will focus on tryptophan metabolism with the project framed around kynurenine as a candidate metabolic biomarker in TSC.

The research seeks to characterize the metabolic landscape of cells affected by TSC to determine what supports their survival and growth, with the ultimate aim of identifying biomarkers that can inform diagnostics, disease monitoring, and development of sustainable therapeutic strategies. TSC is a genetic disease characterized by benign tumors across multiple organs — including brain, lungs, and kidneys — and can cause serious complications such as epilepsy and respiratory difficulties. Although not as aggressive as many cancers, TSC shares disruption of the mTOR pathway, a molecular mechanism implicated in various cancer types. By probing metabolic alterations specific to TSC cells, particularly within tryptophan pathways, the project intends to pinpoint active metabolites that distinguish patient samples from normal values. The project leverages samples acquired from the TS Alliance Biosample repository and applies metabolomic analysis to identify differential metabolites. Following broad metabolomic screening, the team will validate and further analyze promising candidates in the laboratory to confirm their relevance and mechanistic roles. A central component of the project is translational thinking: understanding metabolic dependencies of TSC cells could reveal vulnerabilities that, when targeted, deprive problematic cells of essential nutrients and lead to longer-lasting treatments beyond current options that primarily halt tumor progression.

Previous that discoveries in TSC metabolism may have broader implications; because TSC involves the mTOR pathway similarly implicated in more aggressive cancers, mechanistic insights and potential biomarkers such as kynurenine might inform therapeutic strategies across multiple disease contexts. The seed grant also supports collaboration and open science. Filippakis commits to making generated data publicly available after one year, accelerating research progress by enabling other investigators to build on the findings. The project integrates student training and mentorship:

The research team maintain close partnerships with individuals affected by TSC and their families, drawing on insights from interactions at the international Tuberous Sclerosis Alliance conference to ensure research questions remain aligned with patient needs, and highlighting the importance of centering patient lives alongside mechanistic lab research, aiming for discoveries that tangibly improve daily life for those living with TSC.

This seed-funded investigation into kynurenine and tryptophan metabolism represents a targeted effort to reveal metabolic signatures of TSC, train future clinician-scientists, and foster open, patient-centered research with potential applicability to broader cancer biology.