The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases

Center for Proteomics

The IMM is the hub of a new alliance connecting research efforts across the university in systems biology, clinical and translational sciences, protein chemistry, genomics, and proteomics. This new multidisciplinary science will link the efforts of various centers, bringing together people to promote intellectual exchange and the transfer of expertise in these key fields and beyond.

 

Phone 713.500.2233; fax 713.500.2420

David Gorenstein, Ph.D., Professor and Deputy Director
Kevin Rosenblatt, M.D., Ph.D., Associate Professor

Dr. David Gorenstein has major programs on development of novel technologies (chipand bead-based) for high throughput validation of proteomics biomarkers in cancer, asthma and infectious diseases as part of several major NIH proteomics center grants in biodefense, asthma and cancer. Opportunities for both biomarker discovery using 2D gel MS/MS and LC MS/MS and validation using aptamer-linked Luminex bead-based and microfluidics chip technologies are available for collaborative studies.

Dr. Kevin Rosenblatt's main focus of interest is in the discovery and validation of biomarkers and novel drug targets for molecular pathways of disease in animal and cell models and in human biological fluids and tissues. Mostly, he has focused on protein-based biomarkers and molecular targets because proteins are the "workhorses" of cells and tissues--i.e. proteins carry out the majority of the cell signaling and metabolic reactions necessary for normal physiology, and deranged protein networks are responsible for altered metabolism that results in disease. Thus, while studying the mutations of key genes in the genome and how these mutations effect gene expression is incredibly useful for understanding the molecular basis of many diseases, a knowledge of how protein expression is altered -- which proteins, their relative levels, and their altered regulation at the posttranslational
level -- is necessary for a more complete understanding of a disease process.

For the NIAID Clinical Proteomics Center, Dr. Rosenblatt has set up several protein microarray platforms for highthroughput verification and validation of markers within nanoliters to microliters of cell lyaste material or biological fluids. These innovative technologies include a quantum dot-based reverse phase array platform for analyzing over
10,000 samples in triplicate per microchip and several multiplexed array-based ELISA platforms suitable for rapid analysis of clinical and research samples. His work for the NLHBI Proteomics Center is more discovery based: using several emerging mass spectrometry and micro/nano-flow chromatography dependent systems to find novel protein markers and drug targets within cells, tissues, and biofluids. Using such techniques, Dr. Rosenblatt has discovered several
regulatory pathways downstream of Klotho activation. The Klotho gene produces a protein that regulates endogenous anti-oxidant proteins and modulates several important signaling pathways including the Wnt, IGF-1, FGF, insulin, and TGF-beta signaling pathways; Klotho activation prolongs life when over expressed and leads to rapid early aging when reduced in expression in mouse models. He has found through proteomics and functional genomics experiments that the Klotho protein also confers protective effects on the brain, kidneys, heart, and other organs when overexpressed in these models.