Stephen R Master, MD, PhD

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Associate Professor of Pathology and Laboratory Medicine at the Children's Hospital of Philadelphia
Department: Pathology and Laboratory Medicine

Contact information
Weill Cornell Medicine
525 E. 68th Street - F703
New York, NY 10065
Education:
A.B. (Molecular Biology)
Princeton University , 1990.
Ph.D. (Cell and Molecular Biology)
University of Pennsylvania School of Medicine, 2001.
M.D. (Medicine)
University of Pennsylvania School of Medicine, 2002.
M.S.T.R. (Translational Research)
University of Pennsylvania, 2011.
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Description of Research Expertise

The primary research focus of my laboratory is using systems biology to understand human tumor evolution. Specifically, I am interested in understanding how properties of cellular networks influence the specific sequence of mutations that can give rise to a tumor in a given cell type. Our primary approach utilizes bottom-up, high-resolution mass spectrometry in conjunction with protein microarrays to measure specific changes in the proteome and phospho-proteome characterizing cells at various points along the transformation pathway.

We are currently utilizing neuroblastoma as a model system. Neuroblastoma accounts for ~15% of childhood deaths due to cancer, and as such it is of substantial clinical significance. Additionally, neuroblastoma has several characteristic subtypes that appear to reflect alternative evolutionary pathways. For these reasons, it is an ideal model system in which to investigate the ways that cellular network properties influence and are influenced by specific genomic alterations. As an adjunct to these studies, we are analyzing changes in yeast protein-protein interactions resulting from telomere disruption in order to better understand the ways in which these types of data may contribute to our understanding of mammalian tumor behavior and aging.

A critical component of these investigations will be the ability to not only classify tumors on the basis of a proteomic and/or phospho-proteomic patterns but also to understand the combinations of changes in intracellular pathways that give rise to these patterns. We are currently designing studies that will allow us to create a library of proteomic patterns arising from defined cellular perturbations. We hypothesize that this library, in combination with an extension of bioinformatics techniques that we have previously used to interpret patterns in complex cellular mixtures, will allow us to detect disruption of a large set of known cellular pathways using MS-based proteomic profiling.

In addition to its use as a basic research tool for studying pathways of tumor evolution, such a library would also be of substantial clinical utility. Specifically, it would enable diagnostic interpretation of tumor specimens at the level of functional cellular subnetworks, thereby providing the necessary diagnostic platform on which a “personalized medicine” therapeutic approach can be based. Given the substantial potential of these approaches for clinical laboratory medicine, my laboratory is strongly interested in using this combination of proteomic profiling with novel bioinformatics analyses for both biomarker discovery and diagnostic translation in a number of disease states.

Description of Clinical Expertise

My clinical work is based within the Clinical Chemistry section of the Division of Laboratory Medicine. I have a particular clinical interest in quality control for highly multiplexed genomic (DNA microarray) and proteomic (tandem mass spectrometry or protein microarray) assays.

Selected Publications

Niazi MKK, Chung JH, Heaton-Johnson KJ, Martinez D, Castellanos R, Irwin MS, Master SR, Pawel BR, Gurcan MN, Weiser DA: Advancing clinicopathologic diagnosis of high-risk neuroblastoma using computerized image analysis and proteomic profiling. Pediatr Dev Pathol Jul, 2017 Notes: Epub ahead of print.

Wertheim GB, Luskin MR, Carroll M, Master SR: Microsphere-based assessment of DNA methylation for AML prognosis. Methods Mol Biol(1633), 125-136, 2017.

Storey EP, Master SR, Lockyer JE, Podolak OE, Grady MF, Master CL: Near Point of Convergence after Concussion in Children. Optom Vis Sci 94(1): 96-100, July 2016.

Master CL, Scheiman M, Gallaway M, Goodman A, Robinson RL, Master SR, Grady MF: Vision Diagnoses are Common after Concussion in Adolescents. Clin Pediatr 55(3): 260-7, Mar 2016.

Luskin ML, Gimotty PA, Smith C, Loren AW, Figueroa ME, Harrison J, Sun Z Tallman MS, Paietta EM, Litzow MR, Melnick A, Levine R, Fernandez HF, Luger SM, Carroll M, Master SR *, Wertheim GBW *. : A Clinical Measure of DNA Methylation Predicts Outcome in De Novo AML. JCI Insight 1(9), 2016 Notes: Both authors contributed equally.

DiNardo CD #, Luskin MR #, Carroll M, Smith C, Harrison J, Pierce S, Kornblau S, Konopleva M, Kadia T, Katarjian H, Wertheim GM *, Master SR : Validation of a Clinical Assay of Multi-Locus DNA Methylation for Prognosis of Newly Diagnosed AML Am J Hematol 8(10): 4362-67, 2016 Notes: #Both authors contributed equally.

Garrigan C, Han J, Tolomeo P, Johnson KJ, Master SR, Lautenbach E, Nachamkin I: Evaluation of a research use only luminex based assay for measurement of procalcitonin in serum samples. Am J Trasl Res 8(10): 4362-4369, 2016.

Arsenault PR, Heaton-Johnson KJ, Li LS, Song D, Ferreira VS, Patel N, Master SR (*), Lee FS (*): Identification of Prolyl Hydroxylation Modifications in Mammalian Cell Proteins. Proteomics 15(7): 1259-67, Apr 2015.

Liu KD, Yang W, Go AS, Anderson AH, Feldman HI, Fischer MJ, He J, Kallem RR, Kusek JW, Master SR, Miller ER, Rosas SE, Steigerwalt S, Tao K, Weir MR, Hsu CY: Urine Neutrophil Gelatinase-Associated Lipocalin and Risk of Cardiovascular Disease and Death in CKD: Results From the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis 65(2): 267-74, Feb 2015.

Wei S, Bing Z Yao Y, Master SRM: High Expression of miR-182 in Cytology Specimens of High-Grade Urothelial Cell Carcinoma: A Potential Diagnostic Marker. Acta Cytol 59(1): 109-12, Feb 2015.

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Last updated: 08/28/2017
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