John Lis is a Professor in the Department of Molecular Biology and Genetics. He did his graduate research at Brandeis University and received his Ph.D. in Biochemistry in 1975. His postdoctoral work focused on Drosophila gene regulation and chromosome structure at Stanford University, during which time he was supported by a fellowship from the Helen Hay Whitney Foundation. Dr. Lis joined the faculty at Cornell in 1978. His research program has been supported by the National Institutes of Health, including a MERIT Award, March of Dimes, American Cancer Society, Cornell Biotechnology Institute, and a Proctor and Gamble University Exploratory Research Grant.
The Lis Lab develops and uses a variety of strategies to study the structure of promoters and genes and the mechanisms of their regulation in living cells. Our main model system has been the heat shock genes. These genes can undergo a 200-fold activation of transcription in response to small change in temperature and other cellular stresses. Over the years, we have developed genetic, optical and biochemical approaches that can be applied to study gene transcription and regulation with high precision and specificity in vivo. These include approaches that view the underlying mechanisms at the molecular level and in their native cellular environment. While our studies in the past were focused on a few genes, new genome-wide methods, several which we have developed, allow the interrogation of the entire genome – often with higher precision and sensitivity than our older focused gene studies. The genome-wide approaches are allowing the generality of hypotheses to be tested, and they are providing massive data for generating new hypotheses of how genes are regulated.
We test our proposed molecular mechanisms by examining the consequences of targeted disruption of key protein factors or factor activities. This disruption of factors can be achieved by several strategies. Some strategies are easy and generally applied, such as RNAi, but are not effective at sorting primary from secondary effects. Others can be harder to implement, but are better at rigorously identifying the direct effects of a factor. We frequently use highly-specific small molecule inhibitors of the enzymes involved in transcription and regulation, when such molecules are available. Additionally, we have invested heavily in developing efficient selection methods for RNA aptamers that bind specific factors. RNA aptamers are of particular interest to us as they provide alternatives to small-molecular-weight "drugs" and can be selected in vitro from large combinatorial sequence pool for their affinity to a target protein. Next generation sequencing and use of our multiplex devices in selections have dramatically increased the rate production of RNA aptamers that bind target molecules with high affinity and specificity. These RNA aptamers are large enough to bind tightly to macromolecular surfaces and disrupt/inhibit interactions of a targeted macromolecule. Additionally, these aptamers can be targeted with precision by expressing the RNAs in cell under the control of specific promoters, allowing modulatation or perturbation of molecular interactions with high temporal and spatial precision in tissue culture cells or animals.
My main teaching is focused in BioBM6390, The Nucleus. This course focuses on the structure and function of the eukaryotic nucleus and covers the following topics: genome organization, chromatin structure, transcription factors, gene regulatory mechanisms, RNA processing, DNA replication, and nuclear architecture.
Two different seminar classes that are taught periodically:
1. "Genomics of Gene Regulation". Both an experimental version and a computational version, which was co-taught with Dr. Adam Siepel.
2. "Nucleic Acid Aptamers"
Awards and Honors
- Elected Fellow (2015) National Academy of Sciences
- Core, L. J., Martins, A. L., Danko, C. G., Waters, C. T., Siepel, A. C., & Lis, J. T. (2014). Analysis of nascent RNA identifies a unified architecture of initiation regions at mammalian promoters and enhancers. Nature genetics. 46:1311-20.
- Tome, J. M., Ozer, A., Pagano, J. M., Gheba, D., Schroth, G. P., & Lis, J. T. (2014). Comprehensive analysis of RNA-protein interactions by high-throughput sequencing-RNA affinity profiling. Nature methods. 11:683-688.
- Buckley, M. S., Kwak, H., Zipfel, W. R., & Lis, J. T. (2014). Kinetics of promoter Pol II on Hsp70 reveal stable pausing and key insights into its regulation. Genes & development. 28:14-19.
- Salamanca, H. H., Antonyak, M. A., Cerione, R. A., Shi, H., & Lis, J. T. (2014). Inhibiting heat shock factor 1 in human cancer cells with a potent RNA aptamer. PLoS One. 9:e96330.
- Buckley, M. S., & Lis, J. T. (2014). Imaging RNA Polymerase II transcription sites in living cells. Current Opinion in Genetics & Development. 25:126-130.
- Jonkers, I., Kwak, H., & Lis, J. T. (2014). Genome-wide dynamics of Pol II elongation and its interplay with promoter proximal pausing, chromatin, and exons. eLife. 3:e02407.
- Fuda, N. J., & Lis, J. T. (2013). A new player in Pol II pausing. EMBO Journal. 32:1796-1798.
- Lis, J. T., & Kwak, H. (2013). Control of transcriptional elongation. Annual Review of Genetics. 47:483-508.
- Guertin, M. J., & Lis, J. T. (2013). Mechanisms by which transcription factors gain access to target sequence elements in chromatin. Current Opinion in Genetic Development. 23:116-23.
- Latulippe, D. R., Szeto, K., Ozer, A., Duarte, F. M., Kelly, C. V., Pagano, J. M., White, B. S., Shalloway, D. I., Lis, J. T., & Craighead, H. G. (2013). Multiplexed microcolumn-based process for efficient selection of RNA aptamers. Analytical Chemistry. 85:3417-3424.