Yuri E. Nikiforov, MD, PhD
Professor of Pathology
Vice Chair of the Department of Pathology
Director, Division of Molecular & Genomic Pathology


Yuri 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 and clinical sign out in the Division. He also serves as Co-Director of Multidisciplinary Thyroid Center at UPMC.

Office Location:
Division of Molecular Genomic Pathology
Room 8031
Clinical Lab Building, 8th Floor
3477 Euler Way
Pittsburgh, PA 15213
Contact Information:
Office Telephone: 412-802-6083
Fax: 412-802-6799
Email: nikiforovye@upmc.edu

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Pathology material (see below for the required list) should be sent to:

Attn: Jessica Tebbets
3477 Euler Way, Room 8032
Pittsburgh, PA 15213
Telephone: 412-802-6797
Email: tebbetsjc2@upmc.edu

Bio

Yuri Nikiforov received his MD with Honor from Minsk State Medical Institute in Belarus in 1985 and PhD in Experimental Pathology from the same institution in 1991. He completed an internship in Pathology and served as Assistant Professor at the Department of Pathology at Minsk State Medical Institute until he moved to the U.S. in 1993. He completed his postdoctoral research fellowships in thyroid pathology with Dr. Douglas Gnepp at Rhode Island Hospital/Brown University (1993-1994) and in thyroid cancer genetics with Dr. James Fagin at the Division of Endocrinology, Cedars-Sinai Medical Center/UCLA School of Medicine (1994-1995) and Division of Endocrinology and Metabolism, University of Cincinnati (1995-1997). After completing residency in Anatomic Pathology at the University of Cincinnati in 2000, he joined the Department of Pathology as Assistant Professor and then Associate Professor of Pathology. In August of 2006, Dr. Nikiforov became Director of the Molecular Anatomic Pathology Division at the University of Pittsburgh Medical Center and, in 2013 was promoted to the Vice-Chair for Molecular Pathology and Director of the newly formed Division of Molecular & Genomic Pathology.

Clinical Interests

Dr. Nikiforov's clinical expertise is in thyroid tumors' pathology and genetics and molecular diagnostics of thyroid and other diseases. He serves as the co-director of the Multidisciplinary Thyroid Center at UPMC and as a national and international consultant on thyroid pathology. He is a senior editor of the textbook "Diagnostic Pathology and Molecular Genetics of the Thyroid," now in its 3rd edition. Aiming to decrease a large number of diagnostic thyroid surgeries performed for nodules with unclear cancer risk, he collaborated with Dr. Marina Nikiforova to invent a molecular test for thyroid nodules, the earliest version of which was launched clinically at UPMC in 2007. Now known as a ThyroSeq Genomic Classifier v.3, it is widely used in the U.S. and other countries. In 2014, Dr. Nikiforov formed and led an international group of pathologists and clinicians to reexamine a common type of low-grade thyroid cancer known as "Encapsulated Follicular Variant of Papillary Carcinoma." Based on the generated data, the group proposed in 2016 to reclassify this tumor as "Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP)", removing the word "cancer" from the diagnosis. The new entity was accepted by the World Health Organization in 2017. The reclassification is expected to affect annually >50,000 patients worldwide; it has contributed to the decreasing incidence of thyroid cancer in many countries observed over the last several years. Dr. Nikiforov served on the American Thyroid Association Taskforces that published the Anaplastic Thyroid Cancer Guidelines in 2012 and 2021, and Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer in 2016.

Research Interests

Dr. Nikiforov's research is focused on thyroid cancer genetics, molecular mechanisms of cancer development after exposure to ionizing radiation, and diagnostic molecular markers for thyroid and other cancers. Since 2000, his research lab has been continuously funded by the National Institute of Health and other funding agencies. Dr. Nikiforov's research has led to several scientific discoveries, described below, which have resulted in over 200 peer-reviewed publications and form the basis of Dr. Nikiforov's current work.

(1) The discovery that genes involved in recurrent chromosomal rearrangements in cancer are localized in close 3D proximity to each other in the nuclei of normal cells at the time of exposure to radiation or other genotoxic stresses, providing the structural basis for non-random occurrence of carcinogenic gene fusions in human cancer (Nikiforova Science 2000).

The figure below illustrates that two genes, RET (red) and CCDC6 (green), often forming an oncogenic fusion in thyroid cancer, are located in close spatial proximity in the nuclei of normal thyroid cells, predisposing to the RET-CCDC6 fusion as a result of incorrect repair of double-strand DNA breaks induced in these genes by radiation or other genotoxic exposures.

(2) The discovery of a novel mechanism of BRAF oncogene activation via chromosomal rearrangement leading to the loss of the autoinhibitory N-terminal portion of BRAF and demonstration that in thyroid cancer, chromosomal rearrangements leading to oncogenic gene fusions are the main mechanism of tumorigenesis associated with radiation exposure, in contrast to the same oncogene activation via point mutations in sporadic thyroid cancer (Ciampi J Clin Invest 2005). Later, Dr. Nikiforov and collaborators provided the first demonstration that gene fusions in thyroid cancer developed after the Chernobyl accident have a direct link with radiation dose received by thyroid (Efanov J Natl Cancer Inst 2018).

The figures below illustrate that the MAPK pathway, central for thyroid cancer initiation, is activated predominantly via chromosomal rearrangements leading to gene fusions in radiation-associated thyroid cancer or by point mutations in sporadic thyroid cancer (left panel) and distribution of I-131 dose in post-Chernobyl thyroid cancers with point mutations and gene fusions (right panel).

(3) The discovery of a common transcription-related and ATM kinase-dependent mechanism that rapidly induces contact between homologous chromosomes at the sites of double-strand DNA break (DSB) in human somatic G0/G1 cells, which may enable DSB repair by homologous recombination utilizing the homologous chromosome as a repair template (Gandhi PNAS 2012)

The figure below illustrates contact between p-arms or q-arms of homologous chromosomes in G0/G1 human thyroid cells and fibroblasts (left panel); contact between homologous chromosomes involves short segments of each chromosome, is centered on a DSB, and is preceded by aligning the two homologous regions of each chromosome (right panel).

(4) The discovery of a novel type of gene fusions in thyroid tumors involving the THADA gene on chromosome 2 fused to multiple sites in the region upstream of the IGF2BP3 gene on chromosome 7, and dissecting the mechanism of tumorigenesis which does not involve the formation of a chimeric protein, but rather relies on overexpression of the full-length IGF2BP3 mRNA and protein and increased IGF1 receptor (IGF1R) signaling (Panebianco PNAS 2017).

The figure below illustrates how IGF2BP3 activation via gene fusion and other alterations increases IGF2 translation and IGF1R signaling via PI3K and MAPK cascades, promoting cell transformation and that growth of IGF2BP3-driven tumors may be blocked by IGF1R inhibition, suggesting that IGF2BP3 overexpression in cancer cells may predict sensitivity to anti-IGF1R drugs.

(5) The discovery of the genetic mechanism of hyalinizing trabecular tumors of the thyroid. This tumor, described in 1987 as benign hyalinizing trabecular adenoma, was later reclassified as hyalinizing trabecular tumor and suspected to be a variant of papillary thyroid carcinoma (PTC) based on some reports suggesting that it harbored RET fusions, a hallmark of PTC. In 2019, Dr. Nikiforov's group reported the discovery of PAX8-GLIS3 and PAX8-GLIS1 fusions in these tumors, which are responsible for prominent hyalinization, the most distinct morphologic features of these tumors, and conclusively distinguish them from PTC (Nikiforova Thyroid 2019).

The figure below illustrates the two types of GLIS fusion discovered in hyalinizing trabecular tumors and upregulation of collagens and other extracellular matrix genes in these tumors with deposition of collagen leading to prominent hyalinization.

(6) The description of a new disease entity, "DICER1-positive poorly differentiated thyroid carcinoma of childhood and adolescence." In collaboration with colleagues, Dr. Nikiforov's group uncovered genetic mechanisms of poorly differentiated thyroid carcinomas occurring in young patients, reporting that most of these tumors are driven by DICER1 mutations and they may occur as a manifestation of DICER1 syndrome (Chernock Mod Pathol 2020).

The figure below illustrates the morphology of poorly differentiated carcinoma in children and adolescence (left panel) and detection of DICER1 mutations by Sanger sequencing (right panel).

References

View Dr. Nikiforov's publications on MyBibliography
  • 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; 290,138-41. PMID: 11021799 (subject of an editorial by Savage JR. Cancer. Proximity matters. Science 2000, 290:62-63).
  • 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. PMID: 15630448 (subject of a commentary by Fusco A, et al. A new mechanism of BRAF activation in human thyroid papillary carcinomas. J Clin Invest 2005, 115:20-23).
  • 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 G0/G1-phase human cells. Proc Natl Acad Sci U S A 2012. 109:9454-9. PMID: 22645362.
  • 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. PMID: 23130564.
  • Haugen BR Md, Alexander EK, Bible KC, Doherty G, Mandel SJ, Nikiforov YE, Pacini F, Randolph G, Sawka A, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward D, Tuttle RM Md, Wartofsky L. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 2016. 26:1-133. PMID: 26462967.
  • Nikiforov YE, Seethala RR, Tallini G, Baloch ZW, Basolo F, Thompson LD, Barletta JA, Wenig BM, Al Ghuzlan A, Kakudo K, Giordano TJ, Alves VA, Khanafshar E, Asa SL, El-Naggar AK, Gooding WE, Hodak SP, Lloyd RV, Maytal G, Mete O, Nikiforova MN, Nosé V, Papotti M, Poller DN, Sadow PM, Tischler AS, Tuttle RM, Wall KB, LiVolsi VA, Randolph GW, Ghossein RA. Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors. JAMA Oncol 2016. 2:1023-9. PMID: 27078145.
  • Panebianco F, Kelly LM, Liu P, Zhong S, Dacic S, Wang X, Singhi AD, Dhir R, Chiosea SI, Kuan SF, Bhargava R, Dabbs D, Trivedi S, Gandhi M, Diaz R, Wald AI, Carty SE, Ferris RL, Lee, AV, Nikiforova MN, Nikiforov, YE. THADA fusion is a mechanism of IGF2BP3 signaling in thyroid cancer. Proc Natl Acad Sci USA 2017. 114:2307-2312. PMID: 28193878.
  • Efanov AA, Brenner AV, Bogdanova TI, Kelly LM, Liu P, Little MP, Wald AI, Hatch M, Zurnadzy LY, Nikiforova MN, Drozdovitch V, Leeman-Neill R, Mabuchi K, Tronko MD, Chanock SJ, Nikiforov YE. Investigation of the Relationship Between Radiation Dose and Gene Mutations and Fusions in Post-Chernobyl Thyroid Cancer. J Natl Cancer Inst 2018. 110:371-78. PMID: 29165687.
  • Nikiforova MN, Nikitski AV, Panebianco F, Kaya C, Yip L, Williams MD, Chiosea SI, Seethala R, Roy S, Condello V, Santana-Santos L, Wald AI, Carty SE, Ferris RL, El-Naggar AK, Nikiforov YE. GLIS Rearrangement is a Genomic Hallmark of Hyalinizing Trabecular Tumor of the Thyroid Gland. Thyroid 2019. 29:161-73. PMID: 30648929.
  • Nikiforov YE, Biddinger PW, Thompson LDR (Editors). Diagnostic Pathology and Molecular Genetics of the Thyroid. 3rd Edition, Lippincott Williams & Wilkins, 2019.
  • Chernock RD, Rivera B, Borrelli N, Hill DA, Fahiminiya S, Shah T, Chong AS, Aqil B, Mehrad M, Giordano TJ, Sheridan R, Rutter MM, Dehner LP, Foulkes WD, Nikiforov YE. Poorly differentiated thyroid carcinoma of childhood and adolescence: a distinct entity characterized by DICER1 mutations. Mod Pathol 2020. 33:1264-1274. PMID: 31937902.PMID:
  • Bible KC, Kebebew E, Brierley J, Brito JP, Cabanillas ME, Clark TJ Jr, Di Cristofano A, Foote R, Giordano T, Kasperbauer J, Newbold K, Nikiforov YE, Randolph G, Rosenthal MS, Sawka AM, Shah M, Shaha A, Smallridge R, Wong-Clark CK. 2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer. Thyroid 2021. 31:337-386. PMID: 33728999.

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