Victoria Pereplitsa BelancioVictoria P. Belancio, Ph.D.
Associate Professor

vperepe@tulane.edu

Research Interests:

Only a small proportion of the human genome actually codes for proteins, begging the question of what the rest of our genetic material actually does.  Human retrotransposons, long dismissed as inert repetitive sequences of "junk DNA," are quite active and can profoundly influence our genomes.  Our lab studies one type of these sequences, termed Long Interspersed Element 1 (LINE1 or L1 for short).  Through the use of its two proteins encoded in its bicistronic mRNA (ORF1p and ORF2p), L1 is able to copy and paste itself into new genomic locations.  L1 proteins (particularly ORF2p, which contains two enzymatic functions endonuclease and reverse transcriptase) are also used by other parasitic elements (SINEs, Short Interspersed Elements, and SVA) to move about the genome. Furthermore, L1 machinery is responsible for the generation of processed pseudogenes. L1 is thus the direct and indirect progenitor of a sizable chunk of our genome. Until recently, retrotransposition was believed to take place predominantly in the germ line. The current view is that L1 expression and retrotransposition also occurs in somatic cells, with tumors being particularly permissive for L1 activity.  

Retrotransposition is only one of (albeit the best studied) ways L1 can damage our genome. L1 ORF2p, through its endonuclease, can induce DNA double strand breaks that can introduce a spectrum of mutations if not repaired faithfully, trigger cellular senescence, or even lead to apoptotic cell death.

L1, SINE, and SVA sequences can influence gene function and genome organization long after integration by bringing along their functional promoters, polyadenylation signals, and splice sites; usage of which can alter gene expression or generate novel chimeric transcripts. Additionally, all repetitive sequences can undergo homologous recombination, leading to deletion or duplication of genetic material which can at times be mutagenic. Over the course of evolution, the human genome accumulated a staggering 500,000 copies of L1 and over 1,000,000 copies of the human SINE Alu. Fortunately for our cells, most of these loci are inactive. However,  non-allelic homologous recombination between these highly-related  sequences still causes a wide spectrum of human diseases.

Despite its ubiquity and evolutionary influence, many details of L1 replication cycle,  as well as the  basic functions and interaction profiles of the L1 proteins remain unknown.  Our lab is working to elucidate some of these unknowns from a number of angles and fronts.  Our research interests are focused on the contribution of L1 to human disease (particularly cancer and other age-associated diseases) and include:

  • the RNA and protein biology of L1 as well as the influence of the circadian system (how cells in a complex organism tell time) on L1 activity
  • characterization of the cytotoxic properties of the ORF2p endonuclease domain and cellular response to L1 activity
  • characterization of L1 protein expression and regulation in the mammalian environment

Our lab is unique in that we employ a wide array of basic science strategies to study the L1 replication cycle, from basic molecular biology all the way unto animal models. We routinely perform DNA, RNA,and protein analyses, in addition to tissue culture-based experiments and Next Generation Sequencing approaches.

My lab is a part of the Tulane Cancer Center, Tulane Circadian Cancer Biology group, and COMET, the Consortium of Transposable Elements at Tulane.  If you would like more specifics on any of our many projects, please do not hesitate to contact me.

Education:

Cytology and Genetics Novosibirsk State University, Novosibirsk, Russia
Medical Genetics UAB, Birmingham, AL
Molecular and Cellular Biology  Tulane University, New Orleans, LA

Selected publications:

  1. Wertz GW, Perepelitsa VP, Ball LA. Gene rearrangement attenuates expression and lethality of a nonsegmented negative strand RNA virus. Proc Natl Acad Sci U S A. Mar 31; 95(7):3501-6. 1998 PMID:9520395
  2. Perepelitsa-Belancio V, Deininger P. RNA truncation by premature polyadenylation attenuates human mobile element activity. Nat Genetics. Dec; 35(4):363-6. 2003 [commentaries in 'The Scientist' and 'Nature Reviews Genetics'] PMID:14625551
  3. Belancio VP., Hedges DJ., Deininger P. LINE-1 RNA splicing and influences on mammalian gene expression. Nucleic Acids Research. Mar 22; 34(5):1512-1521 2006PMID:16554555
  4. Xing J., Wang H., Belancio VP., Cordaux R., Deininger P., and Batzer MA.. "Emergence of new primate genes by retrotransposon-mediated sequence transduction" Proc Natl Acad Sci USA. Nov 21;103(47):17608-13. 2006PMID:17101974
  5. Belancio VP., Roy-Engel AM., Pochampally RR., and Deininger P. Somatic expression ofLINE-1 elements in human tissues. Nucleic Acids Research.Jul 1;38(12):3909-22, 2010 PMID:20215437
  6. Belancio VP., Roy-Engel A., and Deininger. P. All y'all need to know 'bout retroelements in cancer. Seminars in Cancer Biology.Aug;20(4):200-102010 PMID:20600922 [among most cited Seminars in Cancer Biology articles published since 2010http://www.journals.elsevier.com/seminars-in-cancer-biology/most-cited-articles/]
  7. Sokolowski M., deHaro D., Kines KJ., Christian C., Belancio VP. Characterization of self-interaction and cellular localization of L1 ORF1p using mammalian two hybrid system. PLoS ONE. December 8(12): e82021, 2013
  8. Deharo DL., Kines KJ., Sokolowski M., Dauchy RT., Streva VA., Hill SM., Hanifin JP., Brainard GC., Blask DE., Belancio VP., Regulation of L1 expression and retrotransposition by melatonin and its receptor; implications for cancer risk associated with light exposure at night. Nucleic Acids Research. Aug 1;42(12):7694-707,2014
  9. Kines KJ., Sokolowski M., Christian C., Deharo D., Belancio VP.Potential for genomic instability associated with retrotranspositionally-incompetent L1 loci. Nucleic Acids Research.Aug 20;42(16):10488-502 2014
  10. Sokolowski M., deFreece C., Servant G., Kines KJ., Deharo DL., Belancio VP. Development of a monoclonal antibody specific to the endonuclease domain of the human LINE-1 ORF2. Mobile DNA Dec 10;5(1):29 2014
  11. Belancio VP., Deininger P., Blask DE., Hill SM., Jazwinski SM. The Aging Clock and Circadian Control of Metabolism and Genome Stability. Review. Frontiers in Genetics of Aging Jan 14;5:455 2015
  12. Hill SM., Belancio VP., Dauchy RT., Brimmer S., Xiang S., Mao L., Hauch A., Lundberg P., Sommers W., Yuan L., Frash T., Blask DE. Invited Review. Melatonin an inhibitor of breast cancer. Journal of Endocrine Related Cancer, Jun;22(3):R183-204, 2015 [recognized among best papers published by this journal in 2015]
  13. Belancio VP. LINE-1 activity as molecular basis for genomic instability associated with light exposure at night. Journal of Mobile Genetic Elements 2015
  14. Xiang S., Dauchy RT., Hauch A., Mao L., Wren MA., Yuan L., Belancio VP., Mondal D., Frasch T., Blask DE., Hill SM. =""> 2015
  15. Mao L., Dauchy RT., Blask DE., Slakey L., Zeringue S., Yuan L., Hauch A., Belancio VP., Dauchy EM., Hill SM. Melatonin suppression of aerobic glycolysis (Warburg effect), survival signaling, and metastasis in human leiomyosarcoma. Journal of Pineal Research, Mar;60(2):167-77,2016
  16. Christian CM., Kines KJ., Sokolowski M., deHaro D., Belancio VP. Identification of L1 ORF2p Sequence important to retrotransposition using Bipartile Alu Retrotransposition (BAR) assay. Nucleic Acids Research, Jun2;44(4818-34),2016
  17. Kines KJ., Sokolowski M., deHaro D., Smither ME., Christian CM., Belancio VP. The endonuclease domain of the LINE-1 ORF2 protein can tolerate multiple mutations. Mobile DNA, Apr 19;7:8, 2016
  18. Christian CM., Kines KJ., Belancio VP. The importance of L1 ORF2p cryptic sequence to ORF2p fragment-mediated cytotoxicity. Mobile Genetic Elements, Jun 20;6(4), 2016
  19. Dauchy R., Wren-Dail M., Hoffman A., Hanifin J., Warfield B., Brainard G., Hill S., Belancio VP., Dauchy E., Blask DE. Daytime Blue-Enriched LED Light Exposure Enhances the Nighttime Melatonin Amplitude: Consequences for CircadianRegulation of Rodent Metabolism and Physiology. Comparative Medicine, 66(5):373-383. 2016
  20. Deininger P. and Belancio VP. The complexity of LINE-related RNA expression. Retrotransposons and Transposons. Lab protocol series METHODS in MOLECULAR BIOLOGY (Springer), Jun 2;44(10):4818-34, 2016
  21. Servant G., Wagstaff BJ., Streva V., Derbes RS., Neeland M., Belancio VP., Gasior SL., Damert A., Schumann, Deininger P., Roy-Engel AM. Regulation of non-LTR Retrotransposon by the NER pathway is associated with L1 ORF1p. Genetics, Jan;205(1):139-153, 2017
  22. P. Deininger, ME. Morales, TB. White, M. Baddoo, DJ Hedges, G. Servant, ME. Smither, M. Concha, DL. DeHaro, EK. Flemington, VP. Belancio A comprehensive approach to expression of L1 loci. Nucleic Acids Research, Mar 17;45(5):e31, 2017
  23. Christian CM., Sokolowski M., deHaro D., Kines KJ., and Belancio VP. Involvement of conserved amino acid in the C-terminal region of LINE-1 ORF2p in retrotransposition. Genetics 2017
  24. Sokolowski M., Chynces TM., deHaro D., Christian CM., and Belancio VP. Truncated ORF1 proteins can suppress LINE-1 retrotransposition in trans. Nucleic Acids Research, May 19;45(9):5294-5308, 2017

Complete List of Published Work in MyBibliography:

http://www.ncbi.nlm.nih.gov/sites/myncbi/victoria.belancio.1/bibliograpahy/40556199/public/?sort=date&direction=ascending

Books:

Chronobiology and rhythms in relation to health, ageing and longevity. Edited by Belancio VP., Hill SM, and Jazwinski SM. Volume V in Healthy Ageing and Longevity series, Springer, series editor Rattan S. (2017)

Pending patents:

U.S. Patent application 60/445,945 (filed on February 7, 2003).
Deininger, Prescott L. and Victoria Perepelitsa Belancio

Entitled:Mammalian Retrotransposable Elements

U. S. Patent application 14/943,942 (filed on November 14, 2015).
Sokolowski Mark and Belancio Victoria P.
Entitled: ANTIBODIES THAT INHIBIT LONG INTERSPERSED ELEMENT-1 RETROTRANSPOSON ENDONUCLEASE

Selected Invited Talks:

  1. The National Institute on Aging Directors Regional Meeting on Aging Research, New Orleans, April, 2009
  2. Division of Aging Biology New Investigator Forum, Bethesda, MD, May 2009
  3. Melatonin Receptors: Action and Therapeutics. FASEB 2011 Summer Research Conference, Snowmass, CO, June26-July 1, 2011
  4. Mobile DNA and Mammalian Genomes. FASEB 2011 Summer Research Conference, Snowmass, CO, August 7-12, 2011
  5. A New Horizon of Retrotransposon Research, International Symposium, Kyoto, Japan, July 31-August 4, 2012
  6. The Biology of Aging Colloquium, Ellison Medical Foundation, Woods Hole, MA, August, 2012
  7. Mobile DNA and Mammalian Genomes. FASEB 2013 Summer Research Conference, Big Sky, MO, June 7-14, 2013
  8. 2013 Annual Meeting of Gerontological Society of America, New Orleans, November 19-22, 2013
  9. Carnegie Institution of Science, Department ofEmbryology, Baltimore, December 15, 2014
  10. Mobile DNA in Mammalian Genomes. FASEB 2015 Summer Research Conference, West Palm Beach, FL, June 7-14, 2015
  11. Duquesne University, Department of Pharmacology, March, 2016
  12. Masonic Cancer Center University of Minnesota, Center for Genome Engineering, February, 2017
  13. Mobile DNA and Mammalian Genomes. FASEB 2017 Summer Research Conference, Big Sky, MO, June, 2017
  14. Johns Hopkins University, Department of Pathology and Oncology, November, 2017

Honors and Awards:

2010-present - Director of the Tulane Cancer Center seminar Series

2010 - Louisiana Cancer Research Consortium Award for Outstanding Scientific Achievement in the Genetics program,

2012 - Kavli fellow, the U. S. National Academy of Scienceand Alexander von Humboldt Foundation 18th annual German-American Kavli Frontiers of Science symposium,Potsdam, Germany (by invitation only)

2015 - NCI-sponsored work-shop "The Role of Mobilome in Cancer" to identify and evaluate emerging research areas with high potential for advancing our understanding of cancer processes and contributing to the NCI research portfolio, NCI Shady Grove campus, Rockville, MD(by invitation only)

2015 - James de la Houssaye Mentor Award Greater New Orleans Science and Engineering Fair

2016-present - Emmy Noether Student to Scientist Award selection committee

2017 - Elected to serve as a co-organizer of the FASEB Mobile elements and Genomes conference in 2019

Current Funding:

NIH, Ladies Leukemia League, Edward G. Schlieder Foundation

Past Funding:

DOD, NIH, The Ellison Medical Foundation, Kay Yow Cancer Fund/V Foundation, Life Extension Foundation, BORSF

Current and former trainees:

2017- present - Ben Freeman, Tulane BMS graduate student

2015-2017 - May Chynces, Graduate student Multidisciplinary Program in Aging

2014-2017 - Madison Smither, Ben Franklin High School intern (Jefferson Scholar, The University of Virginia

2012-2017 - Dr. Mark Sokolowski, BMS graduate student (postdoc at Masonic Cancer Center, University of Minnesota, Minneapolis, MN)

2013-2016 - Dr. Claiborne M. Christian, BMS graduate program (postdoc at St. Jude Children's Research Hospital, Memphis, TN)

2009- 2016 - Dr. Kristine Kines, postdoc. (scientist at theCenters for Disease Control and Prevention, Atlanta, GA)

2009-2010 - Angela Liu, Environmental Health Science master student. (Ph.D. program in epidemiology at the University of North Carolina at Chapel Hill)

2011-2012 - Lakshya Bajaj, Hayward Human Genetics master student, (graduate studentat Baylor College of Medicine Graduate School of Biomedical Sciences

2013-2014 - James Flotken, Tulane undergraduate student intern (Tulane School of Medicine)

Member:

COMET (Consortium of Transposable Elements at Tulane)

Tulane Cancer Center
http://tulane.edu/som/cancer/research/people/victoria-p-belancio.cfm

Tulane Circadian Cancer Biology Group
http://tulane.edu/som/departments/scb/CCBG/members.cfm

Tulane Center for Aging
http://tulane.edu/som/aging/mission-vision.cfm