• PhD, Purdue University
• NIH International Postdoctoral, University of Freiburg, Germany
• Postdoctoral Associate, Johns Hopkins Medical School

Chromosome Organization and Function in the Cell Nucleus

We are taking a multi-disciplinary approach by combining the tools of cell biology, genomics, high resolution three dimensional microscopy and in-house developed state-of-the art computer imaging approaches to study the spatial organization and function of DNA replication sites, transcriptional sites and, most recently, chromosome territories inside the cell nucleus. Of major interest is to develop these studies in human cancer cells where perturbations occur in genomic organization and regulation and during differentiation of human skin cells where major switches in transcriptional programming occur.

Our studies of large subsets of chromosomes (8-10 chromosome pairs) have elucidated probabilistically preferred 3-D interchromosomal networks that are cell type specific in normal diploid human fibroblasts, keratinocytes and luminal epithelial breast cells. In addition, characteristic changes in the interchromosomal networks were found as the cells progressed through the cell cycle and during differentiation of keratinocytes into skin cells. Most strikingly, we discovered a nearly complete reorganization of the interchromosomal network in a malignant human breast cell (MCF10Ca1A) which was originally derived from a normal luminal ductal epithelial breast cell line (MCF10A). We propose that these alterations in chromosomal organization are reflecting corresponding alterations in the genomic programing of these cells. Consistent with this, gene expression microarray analysis revealed massive changes in gene expression between the normal and malignant cell lines.

In a related project, we are studying the 3-D organization (topology) of individual chromosome territories in the cell nucleus using a 6-probe multi-FISH approach that extends from one end of each chromosome to the other. We are particularly interested in determining whether the specific chromosomes in the malignant cells show characteristic alterations in their 3-D organization.

• Fritz AJ, Sehgal N, Pliss A, Xu J and  Berezney R. (2019) Chromosome territories and the global regulation of the genome,  Genes Chromosomes Cancer 58, 407-426
• N. Sehgal, A. J. Fritz, J. Vecerova, H. Ding, Z. Chen, B. Stojkovic, S. Bhattacharya, J. Xu and R. Berezney (2016) Large-scale Probabilistic 3D Organization of Human Chromosome Territories, Human Molecular Genetics 25, 419-436 [awarded cover page and lead article; cited by the “Faculty of 1000” as being of special significance in the field]
• N. Sehgal, B. Seifert, H. Ding, Z. Chen, B. Stojkovic, S. Bhattacharya, J. Xu and R. Berezney (2016) Reorganization of the Interchromosomal Network During Keratinocyte Differentiation, Chromosoma,published online October, 2015: DOI 10.1007/s8004/2-015-0546-5
• H. Ding, B. Stojkovic, Z. Chen, A. Hughes, L.Xu, A. Fritz, N.Sehgal, R. Berezney and J. Xu (2016) Chromatic Kernel and its Applications, Journal of Combinatorial Optimization, in press
• F. Quintero-Rivera et. al [R. Berezney is the 13 author in a list of 22] (2015) MATR3 Disruption in Human and Mouse Associated with Bicuspid Aortic Valve, Aortic Coarctation and Patent Ductus Arteriosus, Human Molecular Genetics 24, 2375-2389.
• A. Pliss, A. N. Kuzmin, A. V. Kachynski, A. Baev, R. Berezney and P.N. Prasad (2015) Fluctuations and Synchrony of RNA Synthesis in Nucleoli, Integrative Biology 7, 681-692.
• Z. Chen, H. Ding, D. Chen, X. Wang, A. Fritz, N. Sehgal, R. Berezney, and J. Xu (2015) Mining k-Median Chromosome Association Graphs from a Population of Heterogeneous Cells, Proc. 6th ACM Conference on Bioinformatics, Computational Biology, and Health Informatics, 47-56. [peer reviewed proceedings]
• A. Pliss, A. J. Fritz, B. Stojkovic, H. Ding, L. Mukherjee, S. Bhattacharya, J. Xu and R. Berezney (2015) Non-Random Patterns in the Distribution of NOR-bearing Chromosome Territories in Human Fibroblasts: A Network Model of Interactions, Journal of Cellular Physiology, 130, issue 2, online (7/25/14) DOI: 10.1002/jcp.24726 [awarded editors choice and cover page]
• A. J. Fritz, B. Stojkovic, H. Ding, J. Xu, S. Bhattacharya, D. Gaile, and R. Berezney (2014) Wide-scale Alterations in Interchromosomal Organization in Breast Cancer Cells: Defining a Network of Interacting Chromosomes, Human Molecular Genetics, 23, 5133-5146.
• N. Sehgal, A. J. Fritz, K. Morris, I. Torres, Z. Chen, J. Xu, and R. Berezney (2014) Gene Density and Chromosome Territory Shape, Chromosoma, 123, 499-513.
• A. J. Fritz, B. Stojkovic, H. Ding, J. Xu, S. Bhattacharya, and R. Berezney (2014) Cell Type Specific Alterations in Interchromosomal Networks Across the Cell Cycle, PLOS Computational Biology, 10(10): e1003857. doi:10.1371/journal.pcbi.1003857
• A. Pliss, K. Malyavantham, S. Bhattacharya, and R. Berezney (2013) Chromatin Dynamics in Living Cells: Identification of Oscillatory Motion, Journal of Cellular Physiology, 228, 609-616. [awarded cover page]
• S. N. Zucker, T. Bancroft, D. Place, B. Des Soye, A. Bagati and R. Berezney (2013) A dominant negative Cx43 mutant differentially affects tumorigenic and invasive properties in human metastatic melanoma cells, Journal of Cellular Physiology, 228, 853-859.
• A. J. Fritz, S. Sinha, N.V. Marella and R. Berezney (2013) Alterations in Replication Timing of Cancer Related Genes in Malignant Human Breast Cancer Cells, Journal of Cellular Biochemistry, 114, 1074-1083. [awarded cover page]
• N. Bansal, M. Zhang, A. Bhaskar, P. Itotia, E. H. Lee, L. S Shlyakhtenko, T. T. Lam, A. Fritz, R. Berezney, Y. L. Lyubchenko, W. F. Stafford and R. Thapar (2013) Assembly of the SLIP1-SLBP Complex on Histone mRNA Requires Heterodimerization and Sequential Binding of SLBP Followed by SLIP1, Biochemistry, 52, 520-536.
• B. Stojkovic, R. Berezney and J. Xu, (2013) Gauging Association Patterns of Chromosome Territories via Chromatic Median, Proc. 2013 IEEE Computer Society Conference on Computer Vision and Pattern Recognition. CVPR, 2, 1296-1303.
• Krishnan, T.T. Lam, A Fritz, D. Rempinski, K. O’Loughlin, H. Minderman, R. Berezney, W.F. Marzluff and R. Thapar (2012) The Prolyl Isomerase Pin1 Targets Stem-Loop Binding Protein (SLBP) to Dissociate the SLBP-Histone mRNA Complex Linking Histone mRNA Decay with SLBP Ubiquitination. Molecular and Cellular Biology, 32, 4306-4322.
• S.N. Zucker, J. Zirnheld, A. Bagati, T. M. DiSanto, B. Des Soye, J. Wawrzyniak, K. Etemadi, M. Nikiforov, and R. Berezney (2012) Preferential Induction of Apoptotic Cell Death in Melanoma Cells as Compared to Normal Keratinocytes Using a Non-thermal Plasma Torch. Cancer Biology and Therapy, 13, 1299-1306. [awarded cover page]
• J.L. Zirnheld, S. N. Zucker, T. M. DiSanto, R. Berezney and K. Etemaldi (2010) Nonthermal Plasma Needle: Development and Targeting of Melanoma Cells. IEEE Transactions on Plasma Science, 38, 948-952.
• B. Stojkovic, Y. Zhu, J. Xu, A. J. Fritz, M. J. Zeitz, J. Vecerova and R. Berezney (2010) Computing Maximum Association Graph in Microscopic Nucleus Images. Medical Image Computing and Computer Assisted Intervention (MICCAI) 2: 530-537. [peer reviewed proceedings]
• K.S. Malyavantham, S. Bhattacharya and R. Berezney (2010) The architecture of functional neighborhoods within the Mammalian Cell Nucleus. Advances in Enzyme Regulation, 50, 126-134.
• M.J. Zeitz, N. V. Marella, K.S. Malyavantham, S. Goetze, J. Bode, I. Raska and R. Berezney (2009) Organization of the Amplified Type I Interferon Gene Cluster and Associated Chromosome Regions in the Interphase Nucleus of Human Osteosarcoma Cells. Chromosome Research, 17, 305-319.
• L. Mukherjee, V. Singh, J. Peng, J. Xu, M. J. Zeitz, and R. Berezney (2009) Generalized Median Graphs and Applications. Journal of Combinatorial Optimization, 17, 21-44.
• A.M. Pliss, K. S. Malyavantham, S. Bhattacharya, M.J. Zeitz and R. Berezney (2009) Chromatin Dynamics is Correlated With Replication Timing. Chromosoma, 118,459-470.
• N.V. Marella, S. Bhattacharya, L. Mukherjee , J. Xu and R. Berezney (2009) Cell Type Specific Chromosome Territory Organization in the Interphase Nucleus of Normal and Cancer Cells. Journal of Cellular Physiology, 221, 130-138.
• N.V. Marella, K. S. Malyavantham, J. Wang, S-I. Matsui, P. Liang and R. Berezney (2009) Cytogenetic and cDNA Microarray Expression Analysis of MCF10A Human Breast Cancer Progression Cell Lines. Cancer Research, 69, 5946-5953.
• M.J. Zeitz, K. S. Malyavantham, B. Seifert and R. Berezney (2009) Matrin 3: Chromosomal Distribution and Protein Interactions. Journal of Cellular Biochemistry, 108, 125-133. [awarded cover page]
• M.J. Zeitz, L. Mukherjee, J. Xu, S. Bhattacharya and R. Berezney (2009) A Probabilistic Model for the Arrangement of a Subset of Chromosome Territories in WI38 Human Fibroblasts. Journal of Cellular Physiology, 221, 120-129. [Awarded cover page for # 113, 114 and 115]
• N.V. Marella, B. Seifert, P. Nagarajan, S. Sinha and R. Berezney (2009) Chromosomal Rearrangements During Human Epidermal Keratinocyte Differentiation. Journal of Cellular Physiology, 221, 139-146.
• N.V. Marella, M. J. Zeitz, K.S. Malyavantham, A. Pliss, S.-I. Matsui, S. Goetze, J. Bode, I. Raska and R. Berezney (2008) Ladder-like Amplification of the Type I Interferon Gene Cluster in the Human Osteosarcoma Cell Line MG63. Chromosome Research, 16, 11,777-11,792.
• S. Bhattacharya, R. Acharya, A. Pliss, K. S. Malyavantham, and R. Berezney (2008). A Hybrid Registration Approach for Matching Genomic Structures in Multimodal Microscopic Images of Living Cells. Proceedings of the 2008 International Conference on Image Processing, Computer Vision, and Pattern Recognition (IPCV’08), Vol. II, pp. 217-221. [peer reviewed proceedings]
• K.S. Malyavantham, S. Bhattacharya, W.D. Alonso, R. Acharya and R. Berezney (2008) Spatio-temporal Dynamics of Replication and Transcription Sites in the Mammalian Cell Nucleus. Chromosoma, 117, 553-567.
• K.S. Malyavantham, S. Bhattacharya, M. Barbeitos, L. Mukherjee, J. Xu, F. O. Fackelmayer and R. Berezney (2008) Identifying Functional Neighborhoods within the Cell Nucleus: Proximity Analysis of Early S-Phase Replicating Chromatin Domains to Sites of Transcription, RNA Polymerase II, HP1γ, Matrin 3 and SAF-A. Journal of Cellular Biochemistry, 105, 391-403. [Awarded cover page]