Cancer, Cancer Genetics, Chromatin, Diabetes, Epigenetics, Epithelial Cells, Gene Regulation, Growth Factors and Receptors, IGF-1 Receptor, Insulin, Insulin Receptor, Knockout Mice, Lipid Signaling, Mass Spectrometry, Microarray, Molecular Biology, Oncogenes, Phosphorylation, Protein Kinases, Protein Phosphatases, Tumor Suppressor Genes, Tumorigenesis
Biophysics and Systems Pharmacology [BSP], Cancer Biology [CAB], Genetics and Genomic Sciences [GGS]
AB, Columbia University
MD, PhD, State University of New York at Stony Brook
Postdoctoral Training, Johns Hopkins University
Society of Scholars of the Johns Hopkins University
AACR Outstanding Investigator Award for Breast Cancer Research
The Parsons laboratory seeks to investigate tumor suppressor and oncogene signaling pathways that are altered in human solid tumors using a multidisciplinary approach that includes genetics, biochemistry, bioinformatics, and pathology. Thematic topics that are currently under investigation include dissection of the regulation and function of the PTEN tumor suppressor, determination of the impact of altered PTEN signals in cancer progression and altered energy metabolism, molecular pathogenesis of breast carcinoma initiation and progression, and examination of epigenetic and chromatin reprogramming as consequence of altered cancer signal pathways. Past accomplishments include discovery of PTEN, elucidation of the frequent alteration of the PI3K/PTEN pathway in a wide variety of cancers, generation of mouse models of cancer due to PTEN mutation, and identification of PREX2 as a regulator of PTEN function.
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Parsons R, Li GM, Longley MJ, Fang WH, Papadopoulos N, Jen J, de la Chapelle A, Kinzler KW, Vogelstein B, Modrich P. Hypermutability and mismatch repair deficiency in RER+ tumor cells. Cell 1993 Dec; 75(6).
Parsons R, Li GM, Longley M, Modrich P, Liu B, Berk T, Hamilton SR, Kinzler KW, Vogelstein B. Mismatch repair deficiency in phenotypically normal human cells. Science (New York, N.Y.) 1995 May; 268(5211).
Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science (New York, N.Y.) 1997 Mar; 275(5308).
Liaw D, Marsh DJ, Li J, Dahia PL, Wang SI, Zheng Z, Bose S, Call KM, Tsou HC, Peacocke M, Eng C, Parsons R. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nature genetics 1997 May; 16(1).
Tashiro H, Blazes MS, Wu R, Cho KR, Bose S, Wang SI, Li J, Parsons R, Ellenson LH. Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies. Cancer research 1997 Sep; 57(18).
Myers MP, Stolarov JP, Eng C, Li J, Wang SI, Wigler MH, Parsons R, Tonks NK. P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase. Proceedings of the National Academy of Sciences of the United States of America 1997 Aug; 94(17).
Bose S, Wang SI, Terry MB, Hibshoosh H, Parsons R. Allelic loss of chromosome 10q23 is associated with tumor progression in breast carcinomas. Oncogene 1998 Jul; 17(1).
Li J, Simpson L, Takahashi M, Miliaresis C, Myers MP, Tonks N, Parsons R. The PTEN/MMAC1 tumor suppressor induces cell death that is rescued by the AKT/protein kinase B oncogene. Cancer research 1998 Dec; 58(24).
Podsypanina K, Ellenson LH, Nemes A, Gu J, Tamura M, Yamada KM, Cordon-Cardo C, Catoretti G, Fisher PE, Parsons R. Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems. Proceedings of the National Academy of Sciences of the United States of America 1999 Feb; 96(4).
Simpson L, Li J, Liaw D, Hennessy I, Oliner J, Christians F, Parsons R. PTEN expression causes feedback upregulation of insulin receptor substrate 2. Molecular and cellular biology 2001 Jun; 21(12).
Podsypanina K, Lee RT, Politis C, Hennessy I, Crane A, Puc J, Neshat M, Wang H, Yang L, Gibbons J, Frost P, Dreisbach V, Blenis J, Gaciong Z, Fisher P, Sawyers C, Hedrick-Ellenson L, Parsons R. An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice. Proceedings of the National Academy of Sciences of the United States of America 2001 Aug; 98(18).
Bose S, Crane A, Hibshoosh H, Mansukhani M, Sandweis L, Parsons R. Reduced expression of PTEN correlates with breast cancer progression. Human pathology 2002 Apr; 33(4).
Puc J, Keniry M, Li HS, Pandita TK, Choudhury AD, Memeo L, Mansukhani M, Murty VV, Gaciong Z, Meek SE, Piwnica-Worms H, Hibshoosh H, Parsons R. Lack of PTEN sequesters CHK1 and initiates genetic instability. Cancer cell 2005 Feb; 7(2).
Saal LH, Holm K, Maurer M, Memeo L, Su T, Wang X, Yu JS, Malmström PO, Mansukhani M, Enoksson J, Hibshoosh H, Borg A, Parsons R. PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer research 2005 Apr; 65(7).
Kushner JA, Simpson L, Wartschow LM, Guo S, Rankin MM, Parsons R, White MF. Phosphatase and tensin homolog regulation of islet growth and glucose homeostasis. The Journal of biological chemistry 2005 Nov; 280(47).
Bayascas JR, Leslie NR, Parsons R, Fleming S, Alessi DR. Hypomorphic mutation of PDK1 suppresses tumorigenesis in PTEN(+/-) mice. Current biology : CB 2005 Oct; 15(20).
Saal LH, Johansson P, Holm K, Gruvberger-Saal SK, She QB, Maurer M, Koujak S, Ferrando AA, Malmström P, Memeo L, Isola J, Bendahl PO, Rosen N, Hibshoosh H, Ringnér M, Borg A, Parsons R. Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. Proceedings of the National Academy of Sciences of the United States of America 2007 May; 104(18).
Saal LH, Gruvberger-Saal SK, Persson C, Lövgren K, Jumppanen M, Staaf J, Jönsson G, Pires MM, Maurer M, Holm K, Koujak S, Subramaniyam S, Vallon-Christersson J, Olsson H, Su T, Memeo L, Ludwig T, Ethier SP, Krogh M, Szabolcs M, Murty VV, Isola J, Hibshoosh H, Parsons R, Borg A. Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair. Nature genetics 2008 Jan; 40(1).
Xia W, Nagase S, Montia AG, Kalachikov SM, Keniry M, Su T, Memeo L, Hibshoosh H, Parsons R. BAF180 is a critical regulator of p21 induction and a tumor suppressor mutated in breast cancer. Cancer research 2008 Mar; 68(6).
Yu JS, Koujak S, Nagase S, Li CM, Su T, Wang X, Keniry M, Memeo L, Rojtman A, Mansukhani M, Hibshoosh H, Tycko B, Parsons R. PCDH8, the human homolog of PAPC, is a candidate tumor suppressor of breast cancer. Oncogene 2008 Aug; 27(34).
Szabolcs M, Keniry M, Simpson L, Reid LJ, Koujak S, Schiff SC, Davidian G, Licata S, Gruvberger-Saal S, Murty VV, Nandula S, Efstratiadis A, Kushner JA, White MF, Parsons R. Irs2 inactivation suppresses tumor progression in Pten+/- mice. The American journal of pathology 2009 Jan; 174(1).
Maurer M, Su T, Saal LH, Koujak S, Hopkins BD, Barkley CR, Wu J, Nandula S, Dutta B, Xie Y, Chin YR, Kim DI, Ferris JS, Gruvberger-Saal SK, Laakso M, Wang X, Memeo L, Rojtman A, Matos T, Yu JS, Cordon-Cardo C, Isola J, Terry MB, Toker A, Mills GB, Zhao JJ, Murty VV, Hibshoosh H, Parsons R. 3-Phosphoinositide-dependent kinase 1 potentiates upstream lesions on the phosphatidylinositol 3-kinase pathway in breast carcinoma. Cancer research 2009 Aug; 69(15).
Fine B, Hodakoski C, Koujak S, Su T, Saal LH, Maurer M, Hopkins B, Keniry M, Sulis ML, Mense S, Hibshoosh H, Parsons R. Activation of the PI3K pathway in cancer through inhibition of PTEN by exchange factor P-REX2a. Science (New York, N.Y.) 2009 Sep; 325(5945).
Sosa MS, Lopez-Haber C, Yang C, Wang H, Lemmon MA, Busillo JM, Luo J, Benovic JL, Klein-Szanto A, Yagi H, Gutkind JS, Parsons RE, Kazanietz MG. Identification of the Rac-GEF P-Rex1 as an essential mediator of ErbB signaling in breast cancer. Molecular cell 2010 Dec; 40(6).
Shen-Li H, Koujak S, Szablocs M, Parsons R. Reduction of Pten dose leads to neoplastic development in multiple organs of Pten (shRNA) mice. Cancer biology & therapy 2010 Dec; 10(11).
Hopkins BD, Fine B, Steinbach N, Dendy M, Rapp Z, Shaw J, Pappas K, Yu JS, Hodakoski C, Mense S, Klein J, Pegno S, Sulis ML, Goldstein H, Amendolara B, Lei L, Maurer M, Bruce J, Canoll P, Hibshoosh H, Parsons R. A Secreted PTEN Phosphatase that Enters Cells to Alter Signaling and Survival. Science (New York, N.Y.) 2013 Jun;.
Hodakoski C, Hopkins BD, Barrows D, Mense SM, Keniry M, Anderson KE, Kern PA, Hawkins PT, Stephens LR, Parsons R. Regulation of PTEN inhibition by the pleckstrin homology domain of P-REX2 during insulin signaling and glucose homeostasis. Proceedings of the National Academy of Sciences of the United States of America 2014 Jan; 111(1).
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