Driving Biology Projects are selected specifically because they require the analysis of the spatial distribution of one or more biological compounds in native tissue, either to learn more about the unique biology of these systems or to characterize molecular signatures of selected cell types in patient biopsies. The projects will ultimately demand imaging at both cellular and sub-cellular dimensions, taking advantage of the current state of the art and driving the development of more advanced IMS technologies.
Retinoid Metabolite Imaging in Age-Related Macular Degeneration
This project seeks new insights into retinoid biology directly in human tissue specimens. For example, understanding the molecular basis of Age-Related Macular Degeneration will provide the basis for development of new treatments and approaches to management of the disease.
Research Partner: Rosalie Crouch, Ph.D. Medical University of South Carolina
Imaging Mass Spectrometry to Elucidate Prostate Cancer Development and Progression
This project addresses the need for better clinically validated markers that can assist clinicians with the diagnosis and management of prostate cancer. Using histology-directed molecular profiling and high-resolution imaging mass spectrometry, molecular signatures that distinguish prostate cancer disease states will be elucidated and clinically validated.
Research Partner: Richard M. Caprioli, Ph.D. Vanderbilt University
Molecular Profiling of Pancreatic Progenitor Cell Populations
There is an urgent need to find improved treatments for the growing problem of diabetes. One approach that is being pursued is to replace diseased pancreatic β cells with human embryonic stem cells to produce new insulin-producing cells. However, little is known about the molecular requirements of β cells to properly differentiate. The goal of this work is to elucidate the molecular events involved in the formation and differentiation of pancreatic β cells in order to better direct the differentiation of stem cells into insulin-producing β cells.
Research Partner: Mark A. Magnuson, M.D. Vanderbilt University
MALDI IMS of Semilunar Valve Maturation Towards Pediatric Tissue Engineered Valves
This project will apply high spatial resolution Imaging Mass Spectrometry to understand the developmental stages of heart valve formation. A more complete understanding of valve development guides the development of tissue engineering approaches to treat congenital valve defects.
Research Partner: John E. Mayer, M.D. Harvard Medical School
Proteomics Imaging of Neurotransmitter Transporter-Linked Signalling Networks
This project seeks to characterize the protein response to altered serotonin and choline transporter proteins in the brain. The understanding of these pathways have direct bearing on multiple neuropsychiatric disorders, including autism, depression, schizophrenia, and Alzheimer's disease. High resolution imaging mass spectrometry techniques that are capable of resolving protein expression changes withing brain areas smaller than 1 mm will be used to better characterize the protein level changes in models systems and provide potential new therapeutic drug targets.
Research Partner: Randy D. Blakely, Ph.D. Vanderbilt University
IMS Differentiation of High and Low Risk Breast Lesions
Presently, there is no way to predict the course of progression of breast lesions that may either become malignant disease or may remain indefinitely indolent. This knowledge could save enormous amounts of resources that are currently spent treating women unnecessarily. Molecular profiling techniques will be used to interrogate patient samples that were collected over the past decade to find distinct molecular signatures that can be used to distinguish aggressive from indolent lesions. These data will be used to aid in diagnosis, prognosis, and stratifying patient risk.
Research Partner: Craig Shriver, M.D. Walter Reed Army Medical Center
Cellular Mechanisms of Renal Glomerular Diseases
The mechanisms of glomerulosclerosis have been elusive due to the technical challenges of studying individual glomerular components in situ or due to artifacts inherent to cell cultures and isolation techniques. The goal of this project is to document macromolecular expression change to specific glomerular structural components, an important step towards understanding molecular mechanisms of glomerulosclerosis.
Research Partner: Billy G. Hudson, Ph.D. Vanderbilt University