RNA interference (RNAi) and CRISPR are widely used to functionally investigate mammalian genomes. It is our goal to develop and optimize these gene perturbation platforms to improve their effectiveness in understanding the biology of diseases.
Loss-of-function genetics has proven essential for interrogating the functions of genes and for probing their roles within the complex circuitry of biological pathways. Kenneth Chang developed genetic approaches for perturbing genes using shRNAs (RNAi), optimized the effectiveness of these shRNA designs, and created shRNA infrastructure and resources for genetic screens in mammalian cells. These resources include shRNA libraries modeled after microRNAs (miRNAs) and algorithms for predicting highly potent shRNA designs. Dr. Chang has performed many genetic screens in cancer cells and has expanded his research to include a significant focus on CRISPR technologies and their applications. The lab’s goal is to leverage these technologies to promote a deeper understanding of cancer pathways and dependencies, with the potential for discovery of new therapeutic targets and generation of disease-relevant models for improving human health. As the Director of the Functional Genomics Shared Resource, Dr. Chang and his lab also provide access to advanced RNAi/CRISPR technologies, construction of custom RNAi/CRISPR libraries, and assists in the design and implementation of genetic screens to support research programs at CSHL and the scientific community.
- New research explains why even targeted therapies eventually fail in lung cancer
- CSHL team finds a way to make shRNA gene knockdown more effective
- New method powerfully boosts efficiency of RNA interference (RNAi) in shutting down genes
- CSHL scientists harness logic of “Sudoku” math puzzle to vastly enhance genome-sequencing capability
- Scientists at Cold Spring Harbor Laboratory hone method to selectively target cancer genes and cells
- RNA Interference Library covers entire human genome
Transcriptional silencing of ALDH2 confers a dependency on Fanconi anemia proteins in acute myeloid leukemia.
23 Apr 2021 | Cancer Discovery
Yang, Zhaolin, Wu, Xiaoli, Wei, Yiliang, Polyanskaya, Sofya, Iyer, Shruti, Jung, Moonjung, Lach, Francis, Adelman, Emmalee, Klingbeil, Olaf, Milazzo, Joseph, Kramer, Melissa, Demerdash, Osama, Chang, Kenneth, Goodwin, Sara, Hodges, Emily, McCombie, W, Figueroa, Maria, Smogorzewska, Agata, Vakoc, Christopher
Processing by RNase 1 forms tRNA halves and distinct Y RNA fragments in the extracellular environment
20 Aug 2020 | Nucleic Acids Research | 48(14):8035-8049
Nechooshtan, G, Yunusov, D, Chang, K, Gingeras, T
The human Origin Recognition Complex is essential for pre-RC assembly, mitosis and maintenance of nuclear structure
6 Aug 2020 | BioRxiv
Chou, H, Bhalla, K, El Demerdash, O, Klingbeil, O, Hanington, Kaarina, Aganezov, S, Andrews, P, Alsudani, H, Chang, K, Vakoc, C, Schatz, M, McCombie, W, Stillman, B
22 May 2020 | iScience | 23(5):101103
Gryder, B, Wachtel, M, Chang, K, El Demerdash, O, Aboreden, N, Mohammed, W, Ewert, W, Pomella, S, Rota, R, Wei, J, Song, Y, Stanton, B, Schafer, B, Vakoc, C, Khan, J
28 Sep 2018 | Science | 361(6409)
Albrengues, J, Shields, M, Ng, D, Park, C, Ambrico, A, Poindexter, M, Upadhyay, P, Uyeminami, D, Pommier, A, Kuttner, V, Bruzas, E, Maiorino, L, Bautista, C, Carmona, E, Gimotty, P, Fearon, D, Chang, K, Lyons, S, Pinkerton, K, Trotman, L, Goldberg, M, Yeh, J, Egeblad, M
22 Feb 2022 | Nature Communications | 13(1):1001
Gutbrod, M, Roche, B, Steinberg, J, Lakhani, A, Chang, K, Schorn, A, Martienssen, R
29 Jan 2022 | Oncogene
Bharathy, Narendra, Cleary, Megan, Kim, Jin-Ah, Nagamori, Kiyo, Crawford, Kenneth, Wang, Eric, Saha, Debarya, Settelmeyer, Teagan, Purohit, Reshma, Skopelitis, Damianos, Chang, Kenneth, Doran, Jessica, Kirschbaum, C, Bharathy, Suriya, Crews, Davis, Randolph, Matthew, Karnezis, Anthony, Hudson-Price, Lisa, Dhawan, Jyotsna, Michalek, Joel, Ciulli, Alessio, Vakoc, Christopher, Keller, Charles
16 Sep 2021 | Cancer Discovery | :candisc.1849.2020
Wei, Yiliang, Huang, Yu-Han, Skopelitis, Damianos, Iyer, Shruti, Costa, Ana, Yang, Zhaolin, Kramer, Melissa, Adelman, Emmalee, Klingbeil, Olaf, Demerdash, Osama, Polyanskaya, Sofya, Chang, Kenneth, Goodwin, Sara, Hodges, Emily, McCombie, W, Figueroa, Maria, Vakoc, Christopher
The human Origin Recognition Complex is essential for pre-RC assembly, mitosis and maintenance of nuclear structure.
1 Feb 2021 | eLife | 10
Chou, Hsiang-Chen, Bhalla, Kuhulika, Demerdesh, Osama, Klingbeil, Olaf, Hanington, Kaarina, Aganezov, Sergey, Andrews, Peter, Alsudani, Habeeb, Chang, Kenneth, Vakoc, Christopher, Schatz, Michael, McCombie, W, Stillman, Bruce
The role of thymocyte selection-associated HMG box protein (TOX) in CD8 T cell differentiation and dysfunction
1 May 2018 | Journal of Immunology | 200(1 Supp):57.36
Scott, A, Philip, M, Camara, S, Shakiba, M, Levy, O, Glickman, M, Chang, K, Schietinger, A