Cecilia Blair Levandowski
An Epigenetic Basis For ΔNp53-Induced Aging
ΔNp53 is a naturally occurring isoform of the transcription factor p53. During ER stress, oxidative stress, and serum deprivation ΔNp53 protein levels rise as this isoform is preferentially translated via an internal ribosomal entry site. When ΔNp53 is overexpressed in mice it results in an early aging associated phenotype with decreased life span, premature development of osteoporosis, decreased learning capacity, and synaptic dysfunction. Previous work in the lab showed that increased expression of ΔNp53 results in increased levels of mRNA coding for the histone H3K79 methyltransferase DOT1L and increased levels of the metabolite 2-hydroxyglutarate (2-HG) when compared to cells expressing wild-type p53. 2-HG is a competitive inhibitor of α-ketoglutarate dependent dioxygenases, which represent a class of enzymes important for demethylation of DNA and histones. These and other data suggest that expression of ΔNp53 may result in epigenetic changes that could accumulate over time and alter gene expression programs. My research focuses on how ΔNp53 might affect these fundamental epigenetic processes and whether similar changes accumulate during the normal aging process.
Research Gate Profile: https://www.researchgate.net/profile/Cecilia_Levandowski
Education
Doctorate of Philosophy Training
September 2014 to Present
Laboratory of Dr. Dylan Taatjes
University of Colorado at Boulder
Department of Chemistry and Biochemistry
Medical Scientist Training Program
August 2012 to Present
University of Colorado School of Medicine
Anschutz Medical Campus
Bachelor of Science in Biology
Graduated May 2008
Davidson College, Davidson, NC
Concentration in Genomics
Research Experience
University of Colorado Boulder
September 2014 to Present
University of Colorado, Boulder, CO
Department of Chemistry and Biochemistry
Position: Graduate Student
Laboratory: Dr. Dylan Taatjes
Project: An Epigenetic Basis For ΔNp53-Induced Aging
University of Colorado Denver
August 2010 to June 2012
University of Colorado Denver Anschutz Medical Campus, Aurora, CO
Position: Professional Research Assistant
Project: NALP1 functional study
PIs/Labs: Dr. Richard Spritz and Dr. Charles Dinarello
National Institute of Health
August 2008 to August 2010
National Health Genome Research Institute (NHGRI), Bethesda, MD
Position: Post-Baccalaureate IRTA fellow
Laboratory: Dr. Francis Collins
Project: Hutchinson-Gilford progeria syndrome (HGPS)
Publications (Note: Name was changed from Cecilia Diane Blair to Cecilia Blair Levandowski in 2012)
•Fant, CB; Levandowski, CB; Gupta, K; Maas, ZL; Moir, JT; Rubin, JD; Sawyer, A; Esbin, M; Rimel, JK; Luyties, O; Marr, MT; Berger, I; Dowell, RD; Taatjes, DJ. TFIID enables RNA polymerase II promoter-proximal pausing. Mol Cell 2020, 78: In Press. (May 21 issue)
•Steinparzer, I; Sedlyarov, V; Rubin, JD; Eislmayr, K; Galbraith MD; Levandowski, CB; Vcelkova, T; Sneezum, L; Wascher, F; Amman, F; Kleinova, R; Bender, H; Andrysik, Z; Espinosa, JM; Superti-Furga, G; Dowell, RD; Taatjes, DJ;* Kovarik, P.* Transcriptional responses to IFNg require Mediator kinase-dependent pause release and mechanistically distinct CDK8 and CDK19 functions. Mol Cell 2019, 76: 485 – 499.
•Dsouza RS, Levandowski C, Slavov D, Graw SL, Allen LA, Adler E, Mestroni L, Taylor MRG. Danon disease: clinical features, evaluation, and management. Circ Heart Fail. 2014 Sep;7(5):843–9. PubMed PMID: 25228319; PubMed Central PMCID: PMC4169002.
•Levandowski CB, Mailloux CM, Ferrara TM, Gowan K, Ben S, Jin Y, McFann KK, Holland PJ, Fain PR, Dinarello CA. NLRP1 haplotypes associated with vitiligo and autoimmunity increase interleukin-1β processing via the NLRP1 inflammasome. Proceedings of the National Academy of Sciences; 2013;110(8):2952–6. PubMed PMID: 23382179; PubMed Central PMCID: PMC3581876.
•Cao K, Graziotto JJ, Blair CD, Mazzulli JR. Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in Hutchinson-Gilford progeria syndrome cells. Sci Transl Med. 2011 Jun 29;3(89):89ra58. PubMed PMID: 21715679.
•Cao K, Blair CD, Faddah DA, Kieckhaefer JE, Olive M, Erdos MR, Nabel EG, Collins FS. Progerin and telomere dysfunction collaborate to trigger cellular senescence in normal human fibroblasts. J. Clin. Invest. 2011 Jul;121(7):2833–44. PubMed PMID: 21670498; PubMed Central PMCID: PMC3223819.
•Olive M, Harten I, Mitchell R, Beers JK, Djabali K, Cao K, Erdos MR, Blair C, Funke B, Smoot L, Gerhard-Herman M, Machan JT, Kutys R, Virmani R, Collins FS, Wight TN, Nabel EG, Gordon LB. Cardiovascular pathology in Hutchinson-Gilford progeria: correlation with the vascular pathology of aging. 2010 Nov;30(11):2301-9. PubMed PMID: 20798379; PubMed Central PMCID: PMC2965471.
•Önen NF, Overton ET, Presti R, Blair C, Powderly WG, Mondy K. Sub-optimal CD4 recovery on long-term suppressive highly active antiretroviral therapy is associated with favourable outcome. HIV Medicine. 2009 Aug;10(7):439–46. PubMed PMID: 19459993.