Yuri Nikiforov, MD, PhD
Professor of Pathology
Vice Chair of Department of Pathology
Dr. Yuri E. Nikiforov, MD, PhD is Vice-Chair for Molecular Pathology and Director, Division of Molecular and Genomic Pathology. Dr. Nikiforov oversees the operations of the Molecular and Genomic Pathology laboratory in the Clinical Lab Building; he oversees and participates in clinical sign out in the Division. He also serves at Co-Director, Multidisciplinary Thyroid Center at UPMC.
Division of Molecular Genomic Pathology
Clinical Lab Building, 8th Floor
3477 Euler Way
Pittsburgh, PA 15213
Office Telephone: 412-802-6083
Clinical ExpertiesDr. Nikiforov's clinical expertise is in surgical pathology of the thyroid gland and in molecular testing of thyroid, brain, colon, melanoma, pancreas, lung, and other tumors.
Research InterestsDr. Nikiforov's research is focused on thyroid cancer genetics and mechanisms of chromosomal rearrangements and other mutations induced by ionizing radiation in thyroid cells and other cell types. Since 2000, Dr. Nikiforov's research activities have led to four scientific discoveries. These discoveries described below have resulted in more than 100 published papers and form the basis of Dr. Nikiforov's current work.
- The discovery that genes involved in recurrent chromosomal rearrangements in cancer cells are localized in proximity to each other in the nuclei of normal human cells at the time of exposure to ionizing radiation or other genotoxic stress (Science, 2000, 290:138-141).
- The discovery that BRAF oncogene can be activated as a result of chromosomal rearrangement (J Clin Invest, 2005,115:94-101).
- The discovery that in thyroid cancer, chromosomal rearrangements represent the main mutational mechanism in tumors arising as a result of exposure to ionizing radiation, whereas point mutations are a mechanism of spontaneous (chemical) carcinogenesis (J Clin Invest, 2005,115:94-101).
- The discovery of ALK activation in thyroid cancer as a result of STRN-ALK fusion (PNAS, 2014).
Current research activities of Dr. Nikiforov's lab are focused on further understanding the molecular mechanisms of radiation-induced carcinogenesis and chromosomal rearrangements in human cells. Specifically, the studies aim to establish the number of double-strand DNA breaks required for the formation of a chromosomal rearrangement after exposure to ionizing radiation and identify the DNA repair mechanisms involved in this process. The results of this research will allow better understanding of carcinogenesis induced by ionizing radiation and help to develop measures for alleviating and preventing the carcinogenic effect of radiation exposure.
Another direction of Dr. Nikiforov's research is centered on finding novel mutations and gene fusions in thyroid cancer using next-generation sequencing and applying the current knowledge in molecular genetics of thyroid cancer to the clinical management of patients with thyroid nodules. Specifically, the studies in progress aim to define the diagnostic utility of molecular markers for preoperative diagnosis of cancer in thyroid fine-needle aspiration (FNA) biopsies and to characterize several novel chromosomal rearrangements discovered in thyroid cancer by next generation sequencing.
Dr. Nikiforov's Research Laboratory Website: http://path.upmc.edu/people/ynlab/index.htm
Awards and Honors
- 2007 - Van Meter Award from American Thyroid Association
- 2010 - Thomas Jefferson Medical College, 2010 Pathology Resident Award Lecture
- 2012 - The Endocrine's Society International Award for Publishing Excellence in The Journal of Clinical Endocrinology & Metabolism (JCEM) in 2011
Selected PublicationsView Dr. Nikiforov's publications on PubMed
Nikiforova MN, Stringer JR, Blough R, Medvedovic M, Fagin JA, Nikiforov YE. Proximity of chromosomal loci that participate in radiation-induced rearrangements in human cells. Science 2000, 290,138-141.
Ciampi R, Knauf JA, Kerler R, Gandhi M, Zhu Z, Nikiforova MN, Rabes HM, Fagin JA, Nikiforov YE. Oncogenic AKAP9-BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer. J Clin Invest 2005,115: 94-101.
Gandhi M, Stringer JR, Medvedovic M, Nikiforov YE. Interphase chromosome folding determines spatial proximity of genes participating in carcinogenic RET/PTC rearrangements. Oncogene 2006, 25:2360-2366.
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, 94:2092-2098.
Zuo H, Gandhi M, Edreira MM, Hochbaum D, Nimgaonkar VL, Zhang P, Dipaola J, Evdokimova V, Altschuler DL, Nikiforov YE. Downregulation of Rap1GAP through epigenetic silencing and loss of heterozygosity promotes invasion and progression of thyroid tumors. Cancer Res. 2010, 70:1389-97.
Nikiforov YE, Ohori NP, Hodak SP, Carty SE, Lebeau SO, Ferris RL, Yip L, Seethala RR, Tublin ME, Stang MT, Coyne C, Johnson JT, Stewart AF, Nikiforova MN. Impact of Mutational Testing on the Diagnosis and Management of Patients with Cytologically Indeterminate Thyroid Nodules: A Prospective Analysis of 1056 FNA Samples. J Clin Endocrinol Metab. 2011, 96:3390-7. (Recipient the Endocrine Society's International Award for Publishing Excellence in the Journal of Clinical Endocrinology & Metabolism in 2011).
Niemeier LA, Kuffner Akatsu H, Song C, Carty SE, Hodak SP, Yip L, Ferris RL, Tseng GC, Seethala RR, Lebeau SO, Stang MT, Coyne C, Johnson JT, Stewart AF, Nikiforov YE. A combined molecular-pathologic score improves risk stratification of thyroid papillary microcarcinoma. Cancer. 2012, 118:2069-77.
Nikiforov YE, Nikiforova MN. Molecular genetics and diagnosis of thyroid cancer. Nat Rev Endocrinol. 2011, 30:569-80.
Nikiforova MN, Gandhi M, Kelly L, Nikiforov YE. MicroRNA dysregulation in human thyroid cells following exposure to ionizing radiation. Thyroid. 2011 Mar;21(3):261-6.
Knauf JA, Sartor MA, Medvedovic M, Lundsmith E, Ryder M, Salzano M, Nikiforov YE, Giordano TJ, Ghossein RA, Fagin JA. Progression of BRAF-induced thyroid cancer is associated with epithelial-mesenchymal transition requiring concomitant MAP kinase and TFG? signaling oncogene. Oncogene 2011, 30:3153-62.
Howell GM, Carty SE, Armstrong MJ, Lebeau SO, Hodak SP, Coyne C, Stang MT, McCoy KL, Nikiforova MN, Nikiforov YE, Yip L. Both BRAF V600E Mutation and Older Age (> 65 Years) are Associated with Recurrent Papillary Thyroid Cancer. Ann Surg Oncol 2011, 18:3566-71.
Yip L, Kelly L, Shuai Y, Armstrong MJ, Nikiforov YE, Carty SE, Nikiforova MN. MicroRNA signature distinguishes the degree of aggressiveness of papillary thyroid carcinoma. Ann Surg Oncol 2011, 18:2035-41.
Ghandi M, Nikiforov YE. Suitability of animal models for studying radiation-induced thyroid cancer in humans: evidence from nuclear architecture. Thyroid. 2011, 21:1331-1337.
Evdokimova V, Gandhi M, Rayapureddi J, Stringer JR, Nikiforov YE. Formation of carcinogenic chromosomal rearrangements in human thyroid cells after induction of double-strand DNA breaks by restriction endonucleases. Endocrine-Related Cancer 2012, 19:271-81.
Kabaker AS, Tublin ME, Nikiforov YE, Armstrong ME, Hodak SP, Stang MT, McCoy KL, Carty SE, Yip L. Suspicious ultrasound characteristics predict BRAFV600E-positive papillary thyroid carcinoma. Thyroid 2012, 22:585-9.
Yip L, Farris C, Kabaker AS, Hodak SP, Nikiforova MN, McCoy KL, Stang MT, Smith KJ, Nikiforov YE, Carty SE. Cost impact of routine molecular testing for indeterminate thyroid fine needle aspiration biopsies. J Clin Endocrinol Metab 2012, 97:1905-12.
McCoy KL, Carty SE, Armstrong MJ, Seethala RR, Ohori NP, Kabaker AS, Stang MT, Hodak SP, Nikiforov YE, Yip L. Intraoperative Pathologic Examination in the Era of Molecular Testing for Differentiated Thyroid Cancer. J Am Coll Surg. 2012, 51:1037-44.
Gandhi M, Evdokimova VN, T Cuenco K, Nikiforova MN, Kelly LM, Stringer JR, Bakkenist CJ, Nikiforov YE. Homologous chromosomes make contact at the sites of double-strand breaks in genes in somatic G)/G1-phase human cells. Proc Natl Acad Sci U S A. 2012, 109:9454-9.
Monaco SE, Pantanowitz L, Khalbuss WE, Benkovich VA, Ozolek J, Nikiforova MN, Simons JP, Nikiforov YE. Cytomorphological and molecular genetic findings in pediatric thyroid fine-needle aspiration. Cancer Cytopathol. 2012, 120:342-50.
Aggarwal N, Swerdlow SH, Kelly LM, Ogilvie JB, Nikiforova MN, Sathanoori M, Nikiforov YE. Thyroid carcinoma-associated genetic mutations also occur in thyroid lymphomas. Mod Pathol. 2012, 25:1203-11.
Howell GM, Nikiforova MN, Carty SE, Armstrong MJ, Hodak SP, Stang MT, McCoy KL, Nikiforov YE, Yip L. BRAF V600E Mutation Independently Predicts Central Compartment Lymph Node Metastasis in Patients with Papillary Thyroid Cancer. Ann Surg Oncol. 2013 Jan: 20(1):47-52.
Ohori NP, Singhal R, Nikiforova MN, Yip L, Schoedel KE, Coyne C, McCoy KL, LeBeau, SO, Hodak SP, Carty SE, Nikiforov YE. BRAF mutation detection in indeterminate thyroid cytology specimens: Underlying cytologic, molecular, and pathologic characteristics of papillary thyroid carcinoma. Cancer Cytopathol. 2013, 20:47-52.
Bansal M, Gandhi M, Ferris RL, Nikiforova MN, Yip L, Carty SE, Nikiforov YE. Molecular and Histopathologic Characteristics of Multifocal Papillary Thyroid Carcinoma. Am J Surg Pathol. 2013, 37(10): 1586-91.
Smallridge RC, Ain KB, Asa SL, Bible KC, Brierley JD, Burman KD, Kebebew E, Lee NY, Nikiforov YE, Rosenthal MS, Shah MH, Shaha AR, Tuttle RM. For The American Thyroid Association Anaplastic Thyroid Cancer Guidelines Taskforce. American thyroid association guidelines for management of patients with anaplastic thyroid cancer. Thyroid. 2012, 22:1104-39.
Mehta V, Nikiforov YE, Ferris RL. Use of molecular biomarkers in FNA specimens to personalize treatment for thyroid surgery. Head & Neck. 2013 35(10):1499-506.
Yousem SA, Dacic S, Nikiforov YE, Nikiforova M. Pulmonary Langerhans Cell Histiocytosis: Profiling of Multifocal Tumors Using Next-Generation Sequencing Identifies Concordant Occurrence of BRAF V600E Mutations. Chest. 2013, 143(6):1679-84.
Dettmer M, Vogetseder A, Durso MB, Moch H, Komminoth P, Perren A, Nikiforov YE, Nikiforova MN. MicroRNA Expression Array Identifies Novel Diagnostic Markers for Conventional and Oncocytic Follicular Thyroid Carcinomas. J Clin Endocrinol Metab. 2013, 98:E1-7.
Gandhi M, Evdokimova VN, Cuenco KT, Bakkenist CJ, Nikiforov YE. Homologous chromosomes move and rapidly initiate contact at the sites of double-strand breaks in genes in G0-phase human cells. Cell Cycle. 2013, 12(4):547-52.
Chan JM, Bilodeau E, Celin S, Nikiforov Y, Johnson JT. Ewing sarcoma of the thyroid: Report of 2 cases and review of the literature. Head Neck. 2013 Mar 18. doi: 10.1002/hed.23240. [Epub ahead of print]
Gupta N, Dasyam AK, Carty SE, Nikiforova MN, Ohori NP, Armstrong M, Yip L, Lebeau SO, McCoy KL, Coyne C, Stang MT, Johnson J, Ferris RL, Seethala R, Nikiforov YE, Hodak SP. RAS Mutations in Thyroid FNA Specimens Are Highly Predictive of Predominantly Low-Risk Follicular-Pattern Cancers. J Clin Endocrinol Metab. 2013 98:E914-22.
Leeman-Neill RJ, Brenner AV, Little MP, Bogdanova TI, Hatch M, Zurnadzy LY, Mabuchi K, Tronko MD, Nikiforov YE. RET/PTC and PAX8/PPAR? chromosomal rearrangements in post-Chernobyl thyroid cancer and their association with iodine-131 radiation dose and other characteristics. Cancer. 2013, 119(10):1792-9.
Dettmer MS, Perren A, Moch H, Komminoth P, Nikiforov YE, Nikiforova MN. Comprehensive microRNA expression profiling identifies novel markers in follicular variant of papillary thyroid carcinoma. Thyroid. 2013, 23(11):1383-9.
Nikiforova MN, Wald AI, Roy S, Durso MB, Nikiforov YE. Targeted next-generation sequencing panel (ThyroSeq) for detection of mutations in thyroid cancer. J Clin Endocrinol Metab. 2013, 98(11): E1852-60.
Mehta RS, Carty SE, Ohori NP, Hodak SP, Coyne C, LeBeau SO, Tublin ME, Stang MT, Johnson JT, McCoy KL, Nikiforova MN, Nikiforov YE, Yip L. Nodule size is an independent predictor of malignancy in mutation-negative nodules with follicular lesion of undetermined significance cytology. Surgery. 2013 Oct;154(4):730-6; discussion 736-8.
Roy, S, Durso MB, Wald A, Nikiforov YE, Nikiforova MN. SeqReporter: Automating Next-Generation Sequencing Result Interpretation and Reporting Workflow in a Clinical Laboratory. J Mol Diagn. 2014 Jan;16(1):11-22.
Jung CK, Little MP, Lubin JH, Brenner AV, Wells SA Jr, Sigurdson AJ, Nikiforov YE. The increase in thyroid cancer incidence during the last four decades is accompanied by a high frequency of BRAF mutations and a sharp increase in RAS mutations. J Clin Endocrinol Metab. 2014, 99:E276-85.
Leeman-Neill RJ, Kelly LM, Liu P, Brenner AV, Little MP, Bogdanova TI, Evdokimova VE, Hatch M, Zurnadzy LY, Nikiforova MN, Yue NJ, Zhang M, Mabuchi K, Tronko MD, Nikiforov YE. ETV6-NTRK3 is a common chromosomal rearrangement in radiation-associated thyroid cancer. Cancer 2014, 120:799-807.
Dacic S, Luvison A, Evdokimova V, Kelly L, Siegfried JM, Villaruz LC, Socinski MA, Nikiforov YE. RET rearrangements in lung adenocarcinoma and radiation. J Thorac Oncol. 2014 Jan;9(1):118-20.
Dettmer MS, Perren A, Moch H, Komminoth P, Nikiforov YE, Nikiforova MN. MicroRNA profile of poorly differentiated thyroid carcinomas. J Mol Endocrinol. 2014, 2:181-9.
Kelly LM, Barila G, Liu P, Evdokimova VN, Trivedi S, Panebianco F, Gandhi M, Carty SE, Hodak SP, Luo J, Dacic S, Yu YP, Nikiforova MN, Ferris RL, Altschuler DL, Nikiforov YE. Identification of the transforming STRN-ALK fusion as a potential therapeutic target in the aggressive forms of thyroid cancer. Proc Natl Acad Sci U S A. 2014, 111(11); 4233-4238.