Multiomics

Lipids are important chemical building blocks in the human body, particularly in the central nervous system (CNS) where the lipid content is the highest next to adipose tissue. Apart from roles as chemical building blocks, and perhaps more importantly, lipids function as signaling molecules in the regulation of cellular life span, inflammation, and immunity. Various lipidomic approaches are utilized for the identification and deciphering of the signaling roles of lipids.

A number of lipidomic approaches have been pioneered at the University of Pittsburgh, among them is oxidative lipidomics that focuses on oxidized lipids and analysis of single cell lipidome. Using these newly developed methods, specific oxidized lipids have been identified as cellular death signals, mediators of tumor immunity and inflammation.

These methods are also identified the brain mitochondria (the powerhouse of cells) as having a specific complement of lipids that are different and distinct from all other organs. When the brain is injured, these mitochondria-specific lipids are released into the blood, thus having the ability to aid in diagnosis and prognostication. Imaging lipids at a single-cell level or even subcellular level has become possible only recently. Approaches have been developed using mass spectrometry to detect and explore the localization of lipids in cells. A number of lipidomic approaches have been pioneered at the University of Pittsburgh, among them is oxidative lipidomics that focuses on oxidized lipids and analysis of single-cell lipidome. Using these newly developed methods, specific oxidized lipids have been identified as cellular death signals, mediators of tumor immunity and inflammation.

We envision coupling of the single cell lipidomics maps with protein and DNA maps to obtain a complete understanding of cellular metabolism and signaling. We believe this knowledge will have a transformative impact in diagnostic and therapeutic avenues for CNS disorders.

iPSC

This theme will use the latest techniques to reprogram, expand, and characterize human induced pluripotent stem cells (iPSC) from both healthy and diseased skin or blood tissue. The iPSC will then be turned into specific human cells, including specific components of the nervous system and other tissue cells.

Some applications of this technology include human diseases ‘modeling-in-a-dish’, developing human reporter cell lines via genetic modification, drug screening on pathological human cell types, and potentially developing cell replacement or regenerative therapies.

Bioinformatics

Next-generation sequencing, and other high-throughput technologies have revolutionized the field of medicine with the ability to personalize diagnosis, risk assessment and treatment of patients. Given the massive amount of data generated, there is a greater need for computational resources and tools to analyze, interpret, visualize, and store the information.

As an interdisciplinary science, bioinformatics leverages mathematics, statistics, and computer science to analyze and interpret biological information at the molecular, cellular, and genomic level. Bioinformatics has a profound impact in the better understanding of disease mechanisms, the identification of biomarkers of particular diseases or conditions, characterization of the patients' drug responses, and expediting the progress towards precision medicine.

The Bioinformatics Core is a resource to support the bioinformatics needs of investigators for sequencing datasets generated in house by the HSSC@CHP core at Rangos Research Center, as well as external sources. The essence of a bioinformatics core is to provide a variety of data analysis services, but she also believes in empowering others to be able to do their own analysis through training events and workshops.

Molecular Imaging

Using high-tech software and machinery, the imaging theme creates two- and three-dimensional images in addition to longitudinal quantification. Molecular images provide visualization, characterization and measurements of biological tissue and other living specimens at the cellular and molecular levels.

The Molecular Imaging Core provides the following services: (1) consultation for design of and implementation of in vivo organ/tissue imaging and image-guided interventions as part of investigator-initiated research grants or of inter-/intra-institutional program grants; (2) support to investigators in image acquisition and image-guided interventions; (3) assist in image process and data analysis; and (4) maintain instruments and provide standard supplies for the imaging.

Human Neurocognitive Development

Cognition and brain systems develop significantly from the newborn period through adolescence and into adulthood, establishing lifelong trajectories. Understanding the brain mechanisms that support neurocognitive development can inform how to detect risk for impaired development (e.g., psychopathology, sequelae from traumatic brain injury, stress, or illness) and approaches for supporting optimal development (e.g., cognitive therapy, training, pharmaceuticals, brain stimulation). Neuroimaging approaches including: task and resting state functional Magnetic Resonance Imaging (t- rs- fMRI), brain structural MRI (sMRI), Magnetic Resonance Spectroscopy (MRS), Diffusion Tensor Imaging (DTI), Electroencephalography (EEG), Magnetoencephalography (MEG), Functional near-infrared spectroscopy (fNIRS), and Positron Emission Tomography (PET) are used to map changes in brain structure, function, and neurochemistry that support cognitive development. Identifying normative development will establish a pediatric neurocognitive growth chart needed to assess the impact of impairments or trauma, build predictive models of recovery, and assess recovery progress enhancing life trajectories.