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Research Interests:
Dr. Nikiforov's research is focused on two main areas: (1) understanding the molecular mechanisms of radiation-induced carcinogenesis and chromosomal rearrangements in human cells and (ii) studying molecular basis of thyroid cancer. The first direction, centered on the mechanisms of radiation-induced carcinogenesis, involves the studies of the role of nuclear architecture and interphase proximity between genetic loci in predisposition to chromosomal rearrangements after radiation exposure, dissecting the molecular mechanism of DNA damage and repair after radiation exposure, and studying genetic predisposition to radiation-induced carcinogenesis. The lab currently works to further prove the hypothesis (Science, 2000, 290:138-141) that nuclear architecture and proximity of gene loci in the nuclei of normal human cells predispose to recurrent chromosomal rearrangements after radiation exposure. A sub-direction in this general area involved the studies of the role of chromosome fragility in generation of chromosomal rearrangements, which are conducted in collaboration with Dr. Yuh-Hwa Wang (Wake Forest).
The second direction of Dr. Nikiforov's lab is centered on the identification of novel mutations in various types of thyroid cancer, development of molecular tests applicable to cancer diagnosis in thyroid fine-needle aspiration (FNA) samples, and finding correlations between specific mutations and tumor behavior. The recent efforts of his lab in this area resulted in cloning and characterization of AKAP9-BRAF rearrangement, which was the first demonstration of activation by recombination of an intracellular effector of the MAPK signaling pathway in vivo, and cloning of a novel type of RET rearrangement, HOOK3-RET. The current efforts are directed towards the identification of novel mutations and gene copy change in thyroid cancer and developing molecular tests for thyroid cancer diagnosis in preoperative FNA biopsies. The methodology allowing to perform molecular testing on thyroid FNAs and a panel of diagnostically and prognostically important mutation-based tests developed in his research lab have been recently introduced into routine clinical practice at UPMC.
Dr. Nikiforov's Research Laboratory Website: http://path.upmc.ed/people/ynlab/
Selected Publications:
Nikiforov YE, Biddinger PW, Thompson LDR (Editors). Diagnostic Pathology and Molecular Genetics of the Thyroid. Lippincott Williams & Wilkins, 2009.
Gandhi M, Stringer JR, Nikiforova MN, Medvedovic, M, Nikiforov YE. Gene position within chromosome territories correlates with their involvement in distinct rearrangement types in thyroid cancer cells. Genes, Chromosomes & Cancer 2009, 48: 222-228.
Nikiforov YE, Steward DL, Robinson-Smith TM, Haugen BR, Klopper JP, Zhu Z, Fagin JA, Falciglia M, Weber K, Nikiforova MN. Molecular testing for mutations in improving the fine needle aspiration diagnosis of thyroid nodules. J Clin Endocrinol Metab. 2009, 94(6): 2092-2098.
Chiosea S, Nikiforova M, Zuo H, Ogilvie J, Gandhi M, Seethala RR, Ohori NP, Nikiforov Y. A Novel Complex BRAF mutation Detected in a Solid Variant of Papillary Thyroid Carcinoma. Endocr Pathol. 2009, 20:122-126.
Nikiforova MN, Tseng GC, Steward D, Diorio D, Nikiforov YE. MicroRNA Expression Profiling of Thyroid Tumors: Biological significance and Diagnostic Utility. J Clin Endocrinol Metab. 2008, 93, 1600-1608. (PMCID: PMC2386678)
Nikiforov YE. Thyroid carcinoma: molecular pathways and therapeutic targets. Mod Pathol 2008, 21, Suppl 2:S37-43.
Nikiforov YE. Radiation-induced thyroid cancer: What we have learned from Chernobyl. Endocrine Pathology 2006, 17: 307-317.
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