The Research Metabolomics component of the Center is the keystone for Center structure. It encompasses three main thrusts to drive its success: Basic Science, Translational/Clinical efforts, and Technology Development.
Metabolomics is an approach crafted from basic research and the combining of information from systems in the domains of biology, chemistry, physics, statistics, and engineering. It covers a vast field of small molecule players in cells and tissues, such as sugars, lipids, vitamins, amino acids, lipids, and many other molecules such as those involved in environmental processes. Research performed at GUMC is invaluable to developing this field from a biomedical standpoint, however, active participation by faculty across campuses through the Center is encouraged to extend to important related areas including basic science, environmental science, astrobiology, instrumentation development, and others. There is the opportunity for a sharp increase in interactions with GU faculty with the development of the Center, as there are already requests for collaborations and metabolomics services that currently go unmet, often due to funding limitations; pilot projects will reduce this limitation. The Center can provide analytical capabilities to further strengthen research collaborations regarding environmentally important molecules, for example, and to create a synergy with the Georgetown Environment Initiative (GEI). Strong connections with College faculty adds value and enhances campus-wide partnerships in sciences from medicine to environment, chemistry, fundamental biology, math, and engineering and furthers the objective of systems medicine.
Metabolomics does not begin and end with basic research. Another key consideration is the translation of laboratory research to clinical practice and application. There are some projects currently underway working within these translational parameters, but with the proximity of the GUMC to the hospital, Lombardi Cancer Center and its location in the Greater Washington Area, many more collaborations and translational studies are being developed through the Center. Involving more clinicians in the metabolomics field boosts translational research, while also informing basic research. At the present time, there are many clinicians who are willing to contribute to the metabolomics field in terms of samples, research, and scholarship, but there is no funding to support any studies that may arise — even small pilot endeavors. The Center with its Translational/Clinical thrust makes an effort to strengthen these connections with the hospital, internal and external clinical collaborators, and maximize benefits that can lead to advancement in the field.
Metabolomics, as a relatively new and rapidly developing field, is driven by underlying technology that includes instrumentation, bioinformatics, database mining, and refinement. Drs. Fornace and Cheema have already demonstrated their ability to develop a successful and widely used core facility for metabolomics, the Metabolomics Shared Resource in the Lombardi Comprehensive Cancer Center. This is the only such metabolomics facility in the Washington, DC area and one of first such cores nationally. Leveraging the Waters Center of Innovation, faculty achievements and connections, and GUMC support, modern mass spectrometry (MS) instrumentation has been assembled to support more than 50 investigators and a large grant portfolio has been created. Other metabolomics instrumentation, such as NMR, is also offered in the MSR. Instrumentation is the nidus for modern metabolomics science and is critical for inclusion within the Center in terms of strengthening collaborations and broadening technological capacity and advancement. The MSR core itself, is separate from the Center, but strong connections benefit both the MSR and the Center. With the establishment of the Center, Research Metabolomics faculty are better positioned to further develop the discipline and supportive studies and funding.
The Center leverages collaborations with leading metabolomic laboratories as well as industry partners to promote a robust research arm directed at deepening metabolome coverage with sample enrichment and data acquisition strategies, and more importantly to develop tools for spectral data reduction and interpretation of the underlying biology. Strong collaborations, for example, enables metabolic labeling based metabolomics (IROA Technology). This includes developing quantitative targeted workflows for metabolite panels from several known and central metabolic pathways. Additionally, further partnership with Waters Corporation helps researchers improve targeted and untargeted metabolomics and lipidomics capabilities. Other industry partners have mentioned interest in assisting with equipment, grant writing, training, and pilot sample running and analysis. Other support opportunities in the Center, include specialized training, equipment, and development of certifications programs. The Center will also work on making the DMS (Differential Mobility Spectrometry) as an add-on capability available to investigators for enhancing the selectivity and sensitivity of targeted workflows. A DMS prototype is available to Dr. Fornace through his collaborations funded by separate NIAID R01 and U19 mechanisms. Collaborations with drug discovery programs will be beneficial for investigators interested in the structural elucidation of unknown compounds, as well as for synthesis of metabolomic standards for developing metabolite libraries. Overall this is likely to complement the Research Metabolomics effort directed towards Translational/Clinical research at GUMC and beyond, as well as promoting the systems medicine approach.
Regarding database mining and refinement, bioinformatics is a critical aspect of modern metabolomics, and is a necessity for the large gigabyte size datasets routinely generated in metabolomics profiling studies. In addition to commercial and open source software, the Fornace and Cheema laboratories are actively developing in-house computational tools to enable large-scale processing of metabolomic data. In addition, the CMS actively partners with bioinformatics experts with many years of combined experience in software development and data management, as well as the support for the Bioinformatics and Biostatistics Shared Resource at GUMC. The overall goal is to develop analytical, visualization methodologies, and tools for integration of metabolomics with multi-omics profiling data such as gene and miRNA expression, DNA copy number, whole genome, exome and RNA sequencing, and SNPs profiling data, as well as with clinical information and outcome attributes. Statistical groups can support metabolomic experimental design for cohort studies as well as for post-processing of metabolomics data using advanced statistical methodologies. All of these collaborations can be strengthened, augmenting the field exponentially through the Research Metabolomics-Technology Development elements of the Center. Additionally, grant proposals are increasing and support generated for more equipment to help develop, outside of the Center, the MSR of the GUMC Shared Resources, including augmenting revenue streams from services provided.