Research interests in my laboratory focus on translational chemical biology using a cutting edge metabolomics-based systems biology approach for metabolic biomarker discovery
Metabolomics, the comprehensive analysis of all the detectable metabolites found within a biological sample, promises potential for early diagnosis, monitoring response to therapy and defining disease pathogenesis. By performing global metabolite profiling, new discoveries linking cellular pathways to biological mechanisms are being revealed and shaping our understanding of cell biology, physiology, and medicine.
Profiling of the metabolome is challenging due to the intrinsic heterogeneity of the compounds involved. Moreover, the combined use of high-resolution magnetic resonance spectroscopy and mass spectroscopy platforms allows us to identify and quantify hundreds/thousands of metabolites from cell lines and primary specimens. Therefore, my lab is constantly engaged in developing and optimizing data acquisition and analysis methodologies as well as data mining procedures.
Capitalizing on this expertise, my lab is involved in several collaborative projects:
- “Identification of Novel Metabolic Biomarkers to Predict Response to Therapy and Design Personalized Therapy Regimens in Pediatric Leukemia Patients”. In collaboration with Drs. Amy Fowler and Philip Neff from the Dell Children’s Medical Center Children’s Blood and Cancer Center, this project currently funded by the Hyundai Hope on Wheels Foundation aims to characterize the metabolic profiles of cancer cells and the sera of leukemia childhood patients to derive biomarkers for treatment stratification and therapeutic target identification.
- “Inhibiting Oxidative Phosphorylation: A Novel Strategy in Leukemia”. In collaboration with Dr. Marina Konopleva from UT MD Anderson, this project currently funded by the Cancer Prevention & Research Institute of Texas (CPRIT) aims to perform pre-clinical testing of a novel inhibitor of oxidative phosphorylation in acute myeloid leukemia models. Metabolic flux analysis using 13C stable isotopes are used for understanding drug mechanism
- “Novel 3D Co-Culture Systems as Models of the Bone Marrow Microenvironment for High-Content Metabolomic Drug Screening”. This project partially funded by SPORE Career Development Grant aims to develop high-throughput compatible 3D co-culture systems to examine interactions among cellular populations isolated from pediatric leukemia patients
- “Phase 2 Study of TH-302 for the Treatment of Glioblastoma”. This is a collaborative project with Dr. Andrew Brenner from the Cancer Therapy & Research Center (CTRC) of The University of Texas Health Science Center at San Antonio. The overall goal of this project, currently funded by FDA is to assess the benefit of TH-302, a nitroimidazole prodrug, in glioblastoma patients using molecular imaging and biomarker profiling to reveal which patients are the most likely to benefit from treatment with the agent.
- Collaborative projects focusing on amino acid depletion therapy targeting cysteine (Drs Georgiou, DiGiovanni, and Stone) and kynurenine (Dr. Georgiou) using engineered human enzymes are currently funded by NIH (RO1) and CPRIT, respectively. Metabolomics analysis of cell lines and mice samples are currently employed for monitoring the metabolic response following cancer treatment.
- Another area of intense research focuses on autoimmune diseases; high throughput screening of a library of natural products combined to current drug therapy is used to target the metabolome and define new treatment strategy in inflammatory arthritis and in other non-cancer conditions.