Yuri E. Nikiforov, MD, PhD
Professor of Pathology
Vice Chair of the Department of Pathology
Director, Division of Molecular & Genomic 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 ExpertiseDr. 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.
Dr. 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. His research lab is currently funded by two R01 grants from the National Institute of Health. Since 2000, Dr. Nikiforov's research activities have led to four scientific discoveries. These discoveries described below have resulted in more than 150 published peer-reviewed 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 and demonstration that in thyroid cancer, chromosomal rearrangements represent the main mutational mechanism of tumorigenesis associated with radiation exposure (J Clin Invest, 2005,115:94-101)
- The discovery that homologous chromosomes make contact at the sites of double-strand breaks in genes in somatic G0/G1-phase human cells, suggest that DNA breaks in genes can be repaired in G0/G1 cells by homologous recombination, utilizing the homologous chromosome as a repair template (Proc Natl Acad Sci USA. 2012, 109:9454-59)
- The discovery of ALK activation in thyroid cancer via STRN-ALK fusion, which can serve as a therapeutic target (Proc Natl Acad Sci USA., 2014, 111:4233-8).
- The discovery of THADA fusions to the regions upstream of the IGF2BP3 gene that lead to overexpression of IGF2BP3 and represents a mechanism of increased IGF1R signaling and carcinogenesis for thyroid cancers a possible therapeutic target for IGF1R inhibitors in thyroid and several other cancer types (Proc Natl Acad Sci USA, 2017, 114:2307-2312).
- Dr. Nikiforov led an international multidisciplinary group of pathologists and clinicians to reexamine a common type of low-grade thyroid cancer, the encapsulated follicular variant of papillary carcinoma. Based on the generated follow-up data, the group reclassified this tumor as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), eliminating the word "cancer" from the diagnosis. The reclassification is expected to affect every year an estimated 10,000 patients in the U.S. and 45,000 worldwide who will lose the diagnosis of cancer (JAMA Oncol. 2016, 2(8):1023-9).
Current research activities of Dr. Nikiforov's lab are centered on the discovery and characterization of novel mutations and gene fusions in thyroid cancer using next-generation sequencing (NGS) 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 large NGS-based panels 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 as possible therapeutic targets for cancer treatment. Transgenic mice with thyroid-specific expression of STRN-ALK have been generated and are being characterized.
Another direction of Dr. Nikiforov's research is focused on further understanding the molecular mechanisms of radiation-induced carcinogenesis and chromosomal rearrangements in human cells. Specifically, the studies aim to establish the role of nuclear architecture and chromosome positioning within the nucleus on the generation and repair of double-strand DNA breaks induced by ionizing radiation. 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.Molecular & Genomic Pathology Laboratory Website: http://mgp.upmc.com
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
- 2014 - The Light of Life Foundation Honorary Award for Exemplary Work in Thyroid Cancer Research and Patient Care for 2014.
- 2016 - The Also Pinchera Award from the Italian Thyroid Carcinoma Observatory
NIH ResearchView Dr. Nikiforov's NIH RePORT on nih.gov
Selected PublicationsView Dr. Nikiforov's publications on PubMed
- 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/PPARγ 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): 1383-1389.
- Ohori NP, Wolfe J, Hodak SP, Lebeau SO, Yip L, Carty SE, Duvvuri U, Schoedel KE, Nikiforova MN, Nikiforov YE. "Colloid-Rich" follicular neoplasm/suspicious for follicular neoplasm thyroid fine-needle aspiration specimens: Cytologic, histologic, and molecular basis for considering an alternate view. Cancer Cytopathol. 2013; Dec; 121(12): 718-28.
- 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: 1586-1591.
- 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.
- Buryk MA, Monaco SE, Witchel SF, Mehta DK, Gurtunca N, Nikiforov YE, Simons JP. Preoperative cytology with molecular analysis to help guide surgery for pediatric thyroid nodules. Int J Pediatr Otorhinolaryngol. 2013, 77(10):1697-700.
- Dillon LW, Pierce LC, Lehman CE, Nikiforov YE, Wang YH. DNA topoisomerases participate in fragility of the oncogene RET. PLoS One. 2013 Sep 11;8(9):e75741.
- 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.
- Wharry LI, McCoy KL, Stang MT, Armstrong MJ, Lebeau SO, Tublin ME, Sholosh B, Silbermann A, Ohori NP, Nikiforov YE, Hodak SP, Carty SE, Yip L. Thyroid Nodules (>4 cm): Can Ultrasound and Cytology Reliably Exclude Cancer? World J Surg. 2014, 38:614-621.
- 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; Mar; 111(11): 4233-4238.
- Yip L, Wharry LI, Armstrong MJ, Silbermann A, McCoy KL, Stang MT, Ohori NP, LeBeau SO, Coyne C, Nikiforova MN, Bauman JE, Johnson JT, Tublin ME, Hodak SP, Nikiforov YE, Carty SE. A clinical algorithm for fine-needle aspiration molecular testing effectively guides the appropriate extent of initial thyroidectomy. Ann Surg. 2014 260:163-8.
- Armstrong MJ, Yang H, Yip L, Ohori NP, McCoy KL, Stang MT, Hodak SP, Nikiforova MN, Carty SE, Nikiforov YE. PAX8/PPARγ Rearrangement in Thyroid Nodules Predicts Follicular-Pattern Carcinomas, in Particular the Encapsulated Follicular Variant of Papillary Carcinoma. Thyroid. 2014 Dec;122(12): 873:82.
- Cancer Genome Atlas Research Network (Nikiforov YE among 243 co-authors). Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014 Oct 23;159(3):676-90.
- Nikiforov YE, Carty SE, Chiosea SI, Coyne C, Duvvuri U, Ferris RL, Gooding WE, Hodak SP, LeBeau SO, Ohori NP, Seethala RR, Tublin ME, Yip L, Nikiforova MN. Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay. Cancer. 2014, 120:3627-34.
- Radkay LA, Chiosea SI, Seethala RR, Hodak SP, LeBeau SO, Yip L, McCoy KL, Carty SE, Schoedel KE, Nikiforova MN, Nikiforov YE, Ohori NP. Thyroid nodules with KRAS mutations are different from nodules with NRAS and HRAS mutations with regard to cytopathologic and histopathologic outcome characteristics. Cancer Cytopathol. 2014, 122:873-82.
- Buryk MA, Simons JP, Picarsic J, Monaco SE, Ozolek JA, Joyce J, Gurtunca N, Nikiforov YE, Feldman Witchel S. Can malignant thyroid nodules be distinguished from benign thyroid nodules in children and adolescents by clinical characteristics? A review of 89 pediatric patients with thyroid nodules. Thyroid 2015 Apr;25(4):392-400.
- Buryk MA, Picarsic J, Creary SE, Shaw PH, Simons JP, Deutsch M, Monaco SE, Nikiforov Y, Witchel S. Identification of unique heterozygous germline mutation, STK11 (p.F354L), in a child with encapsulated follicular variant of papillary thyroid carcinoma within 6 months of completing treatment for neuroblastoma. Pediatr Dev Pathol. 2015 Mar 9. [Epub ahead of print]