Rene Opavsky, PhD
Professor
Teaching Profile
Courses Taught
2017,2019-2025
GMS6647 Transcriptional and Translational Control of Cell Growth and Proliferation
2020-2025
GMS6691 Special Topics in Cell Biology and Anatomy
2020-2025
GMS6421 Cell Biology
2017,2023-2025
GMS6061 Nuclear Structure and Dynamics
2021-2025
GMS6064 Tumor Biology
2022-2025
GMS6001 Fundamentals of Biomedical Sciences I
2023-2024
GMS6335 Advanced Stem Cell Biology: Tissue Engineering
Research Profile
Cytosine methylation is a heritable epigenetic modification affecting gene transcription and the integrity of the genome. In human malignancies, aberrant DNA methylation is the most commonly observed epimutation, often manifested by promoter hypermethylation of tumor suppressor genes and hypomethylation of intergenic non-coding regions. The DNA methyltransferases (DNMTs) DNMT1, DNMT3A, and DNMT3B are the enzymes primarily responsible for methylation of CpG dinucleotides in mammalian DNA. Mutations in the coding sequence of DNMT3A are frequently found in human hematologic malignancies indicating that decreased DNMT3A activity may promote tumorigenesis in multiple hematopoietic lineages. Using targeted inactivation of Dnmt3a in mice Opavsky lab showed that Dnmt3a plays a tumor suppressor role in prevention of chronic B-cell lymphocytic leukemia, peripheral T cell lymphoma and myeloproliferative disease. Furthermore, Dnmt3b is a tumor suppressor gene in prevention of MYC-induced T cell lymphomas. Promoter hypomethylation accompanied by increased gene expression was found to be a frequent event in both mouse and human hematologic malignancies.
RESEARCH PROJECTS
Current projects in Opavsky lab focus on evaluation of functions performed by DNMTs in normal and malignant hematopoiesis utilizing mouse models, genome-wide approaches and in vivo functional studies of DNMT target genes. We are in particular interested in a role of promoter hypomethylation in cellular transformation in order to identify oncogenes for therapeutic targeting.
Publications
Academic Articles
2024
Genome-wide methylation profiling of Peripheral T-cell lymphomas identifies TRIP13 as a critical driver of tumor proliferation and survival.
Research square.
[DOI] 10.21203/rs.3.rs-3971059/v1.
[PMID] 38464090.
2024
Genome-Wide Methylation Profiling of Peripheral T-Cell Lymphomas Identifies TRIP13 as a Critical Driver of Tumor Proliferation and Survival.
Epigenomes.
8(3)
[DOI] 10.3390/epigenomes8030032.
[PMID] 39189258.
2024
Overcoming ABCB1 mediated multidrug resistance in castration resistant prostate cancer.
Cell death & disease.
15(8)
[DOI] 10.1038/s41419-024-06949-3.
[PMID] 39090086.
2022
DNMT3A Harboring Leukemia-Associated Mutations Directs Sensitivity to DNA Damage at Replication Forks.
Clinical cancer research : an official journal of the American Association for Cancer Research.
28(4):756-769
[DOI] 10.1158/1078-0432.CCR-21-2863.
[PMID] 34716195.
2021
A noncanonical microRNA derived from the snaR-A noncoding RNA targets a metastasis inhibitor.
RNA (New York, N.Y.).
27(6):694-709
[DOI] 10.1261/rna.078694.121.
[PMID] 33795480.
2021
Decreases in different Dnmt3b activities drive distinct development of hematologic malignancies in mice.
The Journal of biological chemistry.
296
[DOI] 10.1016/j.jbc.2021.100285.
[PMID] 33450231.
2021
Dnmt3b catalytic activity is critical for its tumour suppressor function in lymphomagenesis and is associated with c-Met oncogenic signalling
EBioMedicine.
63
[DOI] 10.1016/j.ebiom.2020.103191.
[PMID] 33418509.
2019
Catalytically inactive Dnmt3b rescues mouse embryonic development by accessory and repressive functions.
Nature communications.
10(1)
[DOI] 10.1038/s41467-019-12355-7.
[PMID] 31558711.
2016
Aberrant Promoter Hypomethylation in CLL: Does It Matter for Disease Development?
Frontiers in oncology.
6
[DOI] 10.3389/fonc.2016.00182.
[PMID] 27563627.
2016
Absence of caveolin-1 leads to delayed development of chronic lymphocytic leukemia in Eμ-TCL1 mouse model.
Experimental hematology.
44(1):30-7.e1
[DOI] 10.1016/j.exphem.2015.09.005.
[PMID] 26435347.
2016
Dnmt3a Is a Haploinsufficient Tumor Suppressor in CD8+ Peripheral T Cell Lymphoma.
PLoS genetics.
12(9)
[DOI] 10.1371/journal.pgen.1006334.
[PMID] 27690235.
2016
Loss of Dnmt3a induces CLL and PTCL with distinct methylomes and transcriptomes in mice.
Scientific reports.
6
[DOI] 10.1038/srep34222.
[PMID] 27677595.
2016
Promoter Hypomethylation and Expression Is Conserved in Mouse Chronic Lymphocytic Leukemia Induced by Decreased or Inactivated Dnmt3a.
Cell reports.
15(6):1190-201
[DOI] 10.1016/j.celrep.2016.04.004.
[PMID] 27134162.
2015
Methylation-independent repression of Dnmt3b contributes to oncogenic activity of Dnmt3a in mouse MYC-induced T-cell lymphomagenesis.
Oncogene.
34(43):5436-5446
[DOI] 10.1038/onc.2014.472.
[PMID] 25639876.
2014
Chronic lymphocytic leukemia cells in a lymph node microenvironment depict molecular signature associated with an aggressive disease.
Molecular medicine (Cambridge, Mass.).
20(1):290-301
[DOI] 10.2119/molmed.2012.00303.
[PMID] 24800836.
2014
Immature truncated O-glycophenotype of cancer directly induces oncogenic features.
Proceedings of the National Academy of Sciences of the United States of America.
111(39):E4066-75
[DOI] 10.1073/pnas.1406619111.
[PMID] 25118277.
2014
Inactivation of Rb and E2f8 synergizes to trigger stressed DNA replication during erythroid terminal differentiation.
Molecular and cellular biology.
34(15):2833-47
[DOI] 10.1128/MCB.01651-13.
[PMID] 24865965.
2014
Tumor suppressor functions of Dnmt3a and Dnmt3b in the prevention of malignant mouse lymphopoiesis.
Leukemia.
28(5):1138-42
[DOI] 10.1038/leu.2013.364.
[PMID] 24292811.
2013
Dormant cancer cells contribute to residual disease in a model of reversible pancreatic cancer.
Cancer research.
73(6):1821-30
[DOI] 10.1158/0008-5472.CAN-12-2067.
[PMID] 23467612.
2013
Essential role for Dnmt1 in the prevention and maintenance of MYC-induced T-cell lymphomas.
Molecular and cellular biology.
33(21):4321-33
[DOI] 10.1128/MCB.00776-13.
[PMID] 24001767.
2012
Loss of Dnmt3b function upregulates the tumor modifier Ment and accelerates mouse lymphomagenesis.
The Journal of clinical investigation.
122(1):163-77
[DOI] 10.1172/JCI57292.
[PMID] 22133874.
2011
E2f1-3 are critical for myeloid development.
The Journal of biological chemistry.
286(6):4783-95
[DOI] 10.1074/jbc.M110.182733.
[PMID] 21115501.
2009
E2f3a and E2f3b contribute to the control of cell proliferation and mouse development.
Molecular and cellular biology.
29(2):414-24
[DOI] 10.1128/MCB.01161-08.
[PMID] 19015245.
2008
Mouse development with a single E2F activator.
Nature.
454(7208):1137-41
[DOI] 10.1038/nature07066.
[PMID] 18594513.
2007
CpG island methylation in a mouse model of lymphoma is driven by the genetic configuration of tumor cells.
PLoS genetics.
3(9):1757-69
[PMID] 17907813.
2007
E2f1, E2f2, and E2f3 control E2F target expression and cellular proliferation via a p53-dependent negative feedback loop.
Molecular and cellular biology.
27(1):65-78
[PMID] 17167174.
2007
Intestinal hyperplasia induced by simian virus 40 large tumor antigen requires E2F2.
Journal of virology.
81(23):13191-9
[PMID] 17855529.
2007
Rb-mediated neuronal differentiation through cell-cycle-independent regulation of E2f3a.
PLoS biology.
5(7)
[PMID] 17608565.
2007
Specific tumor suppressor function for E2F2 in Myc-induced T cell lymphomagenesis.
Proceedings of the National Academy of Sciences of the United States of America.
104(39):15400-5
[PMID] 17881568.
2005
Cloning and characterization of mouse E2F8, a novel mammalian E2F family member capable of blocking cellular proliferation.
The Journal of biological chemistry.
280(18):18211-20
[PMID] 15722552.
2004
A NotI-EcoRV promoter library for studies of genetic and epigenetic alterations in mouse models of human malignancies.
Genomics.
84(4):647-60
[PMID] 15475242.
2002
Linkage on chromosome 10 of several murine retroviral integration loci associated with leukaemia.
The Journal of general virology.
83(Pt 4):819-827
[DOI] 10.1099/0022-1317-83-4-819.
[PMID] 11907331.
2001
Molecular characterization of the mouse Tem1/endosialin gene regulated by cell density in vitro and expressed in normal tissues in vivo.
The Journal of biological chemistry.
276(42):38795-807
[PMID] 11489895.
2000
HTLV-I Tax transrepresses the human c-Myb promoter independently of its interaction with CBP or p300.
Oncogene.
19(17):2155-64
[PMID] 10815807.
2000
Tax oncoprotein trans-represses endogenous B-myb promoter activity in human T cells.
AIDS research and human retroviruses.
16(16):1629-32
[PMID] 11080802.
1998
Up-regulation of p53 by antisense expression of HPV18 E6 oncogene does not influence the level of MN/CA IX tumor-associated protein in HeLa cervical carcinoma cells.
International journal of oncology.
13(5):1081-6
[PMID] 9772303.
Grants
Jun 2022
ACTIVE
Dnmt3b activities in mouse development
Role: Principal Investigator
Funding: NATL INST OF HLTH NIGMS
Dec 2016
– Mar 2021
The Tumor Suppressor Function of Dnmt3a in Chronic Lymphocytic Leukemia
Role: Principal Investigator
Funding: NATL INST OF HLTH NCI
Feb 2015
– Oct 2023
UF Health Cancer Center Pilot Project Grants funded through the Florida Consortium of National Cancer Institute Centers Program
Role: Project Manager
Funding: UF HEALTH SHANDS HOSPITAL
Education
PhD, Molecular Biology
1996
·
Department of Molecular Biology, Institute of Virology, Slovak Academy of Sciences, Bratislava, Slovak Republic
MSc, Biochemistry
1991
·
Comenius University, Bratislava, Slovak Republic
Contact Details
Phones:
- Business:
- (352) 294-8596
Emails:
- Business:
- ropavsky@ufl.edu
Addresses:
- Business Mailing:
-
PO Box 103633
GAINESVILLE FL 32610 - Business Street:
-
CGRC 258
2033 MOWRY RD
Gainesville FL 32610