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The Department of Biomedicine

BBB seminar: Ruth Hogue Angeletti

Proteomics of cancer and signaling

Ruth Hogue Angeletti
Professor, Laboratory for Macromolecular Analysis and Proteomics, Albert Einstein College of Medicine, Bronx, New York, USA

Proteomics provides an unbiased, objective window on the workings of the cell, and is a necessary complement to microarray studies, since mRNA expression does not always correlate to protein expression. For proteomics efforts, whether small scale or large scale, interdisciplinary work is required, involving collaborations among biologists, protein mass spectrometrists, and bioinformatics and biostatistics specialists. The Laboratory for Macromolecular Analysis and Proteomics (LMAP) is organized as a proteomics platform for AECM research in basic science projects, and is collaborating with clinical departments to establish clinical proteomics research.

The projects focused on by the LMAP include: a rat model of liver carcinogenesis, tubulin proteomics and drug resistance, signaling mechanisms in colony stimulating factor-1 (CSF-1) in macrophages, and heterogeneity of glycosylation in therapeutic antibodies. In addition to mass spectrometry and bioinformatics analysis, these experiments also involve laser capture microdissection, affinity sample preparation methods, analysis of posttranslational modifications, and quantitative proteomics methods. Integrating these experimental approaches and facilitating the transition from discovery to hypothesis are works in progress.

 

Dr. Hogue Angeletti has been working with protein analysis and biology since her student days, first on structural and functional aspects of the nerve growth factor as member of Rita Levi Montalcini's group (1967-73). Since 1974 Dr. Hogue Angeletti has worked in the USA, first in the Laboratory of Neuropathology, University of Pennsylvania School of Medicine, in Philadelphia and since 1988 as head of the Department of Developmental and Molecular Biology at the Albert Einstein College of Medicine in Bronx, New York, a forerunner of the current Laboratory for Molecular Analysis and Proteomics at this institution. Her own research has been directed to structural and functional aspects of neuronal proteins, mostly on the adrenomedullary granule proteins chromogranin A, secretogranin II and dopamine beta-hydroxylase, specifically the regulation of parathyroid secretion by chromogranins, chemokines and calcium. Thanks to the wide range of site-specific antibodies developed by Dr. Hogue Angeletti to highly conserved sequences in chromogranin A and secretogranin II, she is today engaged in a continental-spanning network on granin research, which also includes Bergen. By use of these important tools it has been possible to unmask functional aspects of these proteins and their derived peptides in the diffuse neuroendocrine and the immune systems.

Key references:
Angeletti RH et al. 1999. Research technologies: fulfilling the promise. The FASEB Journal, 13: 595-601.
Angeletti RH, D'Amico T, Russell J. 2000. Regulation of parathyroid secretion. Chromogranins, chemokines and calcium. Adv Exp Med Biol, 482: 217-23.
Wang F, Nakouzi A, Angeletti RH et al. 2003. Site-specific characterization of the N-linked oligosaccharides of a murine immunoglobulin M by high performance liquid chromatography/electrospray mass spectrometry. Analytical Biochemistry, 314: 266-80.