B.S. Johns Hopkins University, 2010
M.S. Johns Hopkins University, 2011
8th Year MSTP
4th Year Medical
David L. Spector, PhD, Cold Spring Harbor Laboratory
Identification and Characterization of lncRNAs in Development and Cancer
Allen Yu1, Jan Bergmann2, David L. Spector2
1Stony Brook University, Stony Brook, NY 2Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
Genome-wide transcriptome analysis has uncovered the presence of thousands of long non-coding RNAs (lncRNAs). Although over 95% of putative lncRNAs are not strongly conserved on the sequence level, several studies have indicated roles of lncRNAs in cell cycle control, proliferation, and regulation of transcription. In order to determine the function of lncRNAs in cell-fate determination and how they modulate gene expression, we performed an RNA-seq screen to identify candidates that are differentially expressed between mouse embryonic stem cells versus neural progenitor cells. 46 uncharacterized lncRNAs of interest were identified and expression of a subset was validated by qPCR as well as RNA-FISH. RNA-seq was performed upon knockdown of selected candidates in order to assess potential transcriptome wide changes in gene expression. One lncRNA is of particular interest in that it is conserved in human and also enriched in hepatocellular carcinoma cell lines. Individual knockdown experiments validated downstream targets identified by RNA-seq, which included a panel of proliferation markers and cell cycle regulators. Further characterization of this novel lncRNA will include isoform identification and localization in different tissues. In addition, determining whether or not this lncRNA has an effect on proliferation and growth in liver development or mouse models of cancer, will allow us to potentially use this lncRNA as a marker for hepatocellular carcinoma and/or as a therapeutic target.
(MSTP-supported publications indicated with an *)
Yu AT, Berasain C, Bhatia S, Rivera K, Liu B, Rigo F, Pappin DJ, Spector DL. PHAROH lncRNA regulates Myc translation in hepatocellular carcinoma via sequestering TIAR. Elife. 2021 May 18;10:e68263. doi: 10.7554/eLife.68263. Epub ahead of print. PMID: 34002693.
Chang KC, Diermeier SD, Yu AT, Brine LD, Russo S, Bhatia S, Alsudani H, Kostroff K, Bhuiya T, Brogi E, Pappin DJ, Bennett CF, Rigo F, Spector DL. MaTAR25 lncRNA regulates the Tensin1 gene to impact breast cancer progression. Nat Commun. 2020 Dec 22;11(1):6438. doi: 10.1038/s41467-020-20207-y. PMID: 33353933; PMCID: PMC7755919.
Chang, K.C., Diermeier, S.D.*, Yu, A.T.*, Brine, L.D., Russo, S., Bhatia, S., Alsudani, H., Kostroff, K., Bhuiya, T., Brogi, E., Bennett, C.F., Rigo, F., Spector, D.L.. Assessing the role of the long non-coding RNA MaTAR25 in mammary tumor progression. Nature Communications. 2020, Oct; Pub Status: Accepted
*These authors contributed equally to the work
Yu, A.T., Coritsidis, A., Sharoha, N.. Video Game delusions and Methamphetamine Intoxication in a Suicidal Patient - A Case Report. Journal of the Royal Society of Medicine. 2020, Oct; Pub Status: Minor Revisions.
Maurer MJ*, Spear ED*, Yu AT, Lee EJ, Shahzad S, Michaelis S. Degradation Signals for Ubiquitin-Proteasome Dependent Cytosolic Protein Quality Control (CytoQC) in Yeast. G3: Genes|Genomes|Genetics. 2016;6(7):1853-1866. doi:10.1534/g3.116.027953.
Annaluru N, Muller H, Mitchell LA, Ramalingam S, Stracquadanio G, Richardson SM, Dymond JS, Kuang Z, Scheifele LZ, Cooper EM, Cai Y, Zeller K, Agmon N, Han JS, Hadjithomas M, Tullman J, Caravelli K, Cirelli K, Guo Z, London V, Yeluru A, Murugan S, Kandavelou K, Agier N, Fischer G, Yang K, Martin JA, Bilgel M, Bohutski P, Boulier KM, Capaldo BJ, Chang J, Charoen K, Choi WJ, Deng P, DiCarlo JE, Doong J, Dunn J, Feinberg JI, Fernandez C, Floria CE, Gladowski D, Hadidi P, Ishizuka I, Jabbari J, Lau CY, Lee PA, Li S, Lin D, Linder ME, Ling J, Liu J, Liu J, London M, Ma H, Mao J, McDade JE, McMillan A, Moore AM, Oh WC, Ouyang Y, Patel R, Paul M, Paulsen LC, Qiu J, Rhee A, Rubashkin MG, Soh IY, Sotuyo NE, Srinivas V, Suarez A, Wong A, Wong R, Xie WR, Xu Y, Yu AT, Koszul R, Bader JS, Boeke JD, Chandrasegaran S. Total synthesis of a functional designer eukaryotic chromosome. Science. 2014 Apr 4;344(6179):55-8. PMID: 24674868