Education
BS, Microbiology Immunology & Molecular Genetics, UCLA, 2012
PhD Candidate, Pharmacology, Rutgers University, 2015 - present
CRC system: a flexible, module base editing platform.Research Interests
Genetics, genetic engineering, gene editing, molecular biology, immunology.
Research Summary
Currently, most gene editing technologies rely on the generation of DNA double strand breaks (DSB) to introduce the desired genomic modification. Precise changes to the genome, such as correction of point mutations, require activation of homology dependent repair (HDR). Unfortunately, this process is unreliable due to competing non-homologous end joining (NHEJ) repair mechanisms. DSB can also potentiate genomic instability.
We seek to engineer a precision gene editing system that can be programmed to edit the genome at the nucleotide level. This base editing technology would also bypass the need for DSB. We take advantage of the CRISPR/Cas9 platform in order to recruit activation-induced cytidine deaminase (AID) to serve as our effector protein. Normally, AID is a DNA editing enzyme that catalyzes C to T conversions for somatic hypermutation. In our system, AID serves as the base editor to introduce precise changes at the nucleotide level. The recruitment mechanism is mediated by gRNAs synthetically fused to RNA scaffolds which then bind to specific RNA-interacting proteins to recruit the effector proteins. Our base editing platform will serve as a new and promising method for correcting genetic mutations without the introduction of DSB and HDR. Therapeutic applications include monogenetic diseases such as cystic fibrosis and sickle cell.
Awards & Honors
Member, American Association for Cancer Research
Gallo Award for Scientific Excellence: Podium Presentation, 2017 & 2018
Martin L. Yarmush Award: 1st place, Poster Presentation 2017
Joint student, Rutgers Institute of Quantitative Biomedicine
UCLA Dean's Honor List, 2012
Publications
Nickols NG, Nazarian R, Zhao SG, Tan V, ..., Rettig MB. (2019). “MEK-ERK signaling is a therapeutic target in metastatic castration resistant prostate cancer.” Prostate Cancer Prostatic Dis. https://www.ncbi.nlm.nih.gov/pubmed/30804427
Yue, X., C. Zhang, Y. Zhao, J. Liu, A. W. Lin, V. M. Tan, J. M. Drake, L. Liu, M. N. Boateng, J. Li, Z. Feng and W. Hu (2017). "Gain-of-function mutant p53 activates small GTPase Rac1 through SUMOylation to promote tumor progression." Genes Dev 31(16): 1641-1654. PMC5647935 https://www.ncbi.nlm.nih.gov/pubmed/28947497
Xi, Y., T. Kim, A. N. Brumwell, I. H. Driver, Y. Wei, V. Tan, J. R. Jackson, J. Xu, D. K. Lee, J. E. Gotts, M. A. Matthay, J. M. Shannon, H. A. Chapman and A. E. Vaughan (2017). "Local lung hypoxia determines epithelial fate decisions during alveolar regeneration." Nat Cell Biol 19(8): 904-914. PMC5600325 https://www.ncbi.nlm.nih.gov/pubmed/28737769
Cheng, L. C., V. M. Tan, S. Ganesan and J. M. Drake (2017). "Integrating phosphoproteomics into the clinical management of prostate cancer." Clin Transl Med 6(1): 9. PMC5309189 https://www.ncbi.nlm.nih.gov/pubmed/28197968
V. M. Tan, L. C. Cheng and J. M. Drake (2016). "Complementing genomics and transcriptomics: Phosphoproteomics illuminates systems biology in prostate cancer." Mol Cell Oncol 3(6): e1246075. PMC5160408 https://www.ncbi.nlm.nih.gov/pubmed/28090583
Vaughan, A. E., A. N. Brumwell, Y. Xi, J. E. Gotts, D. G. Brownfield, B. Treutlein, K. Tan, V. Tan, F. C. Liu, M. R. Looney, M. A. Matthay, J. R. Rock and H. A. Chapman (2015). "Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury." Nature 517(7536): 621-625. PMC4312207 https://www.ncbi.nlm.nih.gov/pubmed/25533958
Representative Graduate Courses Taken
Cell and Molecular Pharmacology
Cancer Pharmacology
Bioinformatics
Biostatistics
Biophysical Chemistry
Bioengineering in Biotechnology and Pharmaceutical Industries
Innovation and Entrepreneurship for Science and Technology
Kinetics, Thermodynamics, & Transport Theory
Leadership & Outreach
President, Rutgers Molecular Biosciences Graduate Student Organization, 2016-2018
Student instructor, Citylab at UCLA, 2010-2012