Hugh P. Cam
assistant professor of biology
Ph.D., Harvard University
Fields of Interest
Epigenetics, functional genomics, gene regulatory networks, molecular mechanisms of genome plasticity.
Available genome sequences of many organisms within the last decade and rapid development of new biological tools have offered unprecedented opportunities to peer, in one swoop, essentially into all the molecular innards of life. As we enter this genomic era of biology, one of the grand challenges will be to illuminate the general factors, themes and rules that give life to genomes. Our lab is interested in utilizing a broad range of approaches, from the precision of traditional molecular biology techniques to the power of high-throughput analyses to uncover novel emergent properties of genomes.
Transposon Impact on Gene Regulatory Networks
Genomes are highly dynamic structures, constantly being molded by internal and external forces that could greatly influence cellular functions and the development and evolution of organisms. One of these forces is due to the activity of transposable elements (TEs) or transposons, genetic parasites that could propagate themselves throughout their host genomes. Eukaryotic genomes are replete with TEs that often insert themselves near gene regulatory sequences, and thus, could influence the expressions of nearby genes. We are interested in uncovering the extent to which TEs and their remnants could influence the overall cellular gene regulatory networks. We have recently discovered in the fission yeast Schizosaccharomyces pombe that a family of proteins similar to the human centromeric protein CENP-B could target extant and "extinct" TEs via a host genome surveillance mechanism. In addition to promoting higher-order organization of retrotransposons and suppressing Tf transcription, recombination and transposition, fission yeast CENP-B proteins could bind to hundreds of Tf remnants in the form of solo LTRs that could have a regulatory effect on nearby genes. We hypothesize that CENP-B bound to LTR may act as a versatile regulatory module that could provide "plasticity" to gene networks, helping cells cope with adverse changing environmental conditions. We are employing a combination of genetic and genomic approaches to elucidate the players and mechanisms involved in CENP-B/LTR-mediated gene regulatory networks.
Regulatory Controls of Epigenomes
While the complete sequencing of many eukaryotic genomes including that of human has provided numerous insights into the landscapes of genomes, it is still not clear how genomes of higher eukaryotes with a relatively small set of genes in proportion to their larger genome sizes could sustain complex development and generation of diverse cell types. It has been proposed that a greater repertoire and elaboration of gene regulatory mechanisms could account for the complexity seen in higher eukaryotes. Inheritance and stable maintenance of cellular states by epigenetic means, which do not depend on changes or reshufflings in genomic content, are thought to contribute to the establishment of distinct cell types. Our lab is interested in deciphering factors and mechanisms that allow cells to maintain their overall epigenetic profiles or epigenomes that are essential for their cellular identity under environmental onslaughts such as stress. We are focusing on candidate factors that may have dual roles in epigenetic regulation and stress response. We hypothesize that these factors may behave as "epigenome stabilizers" by facilitating cells to quickly cope with sudden stressful stimuli without permanent modifications to their epigenomes. These epigenome stabilizers could be the critical players that act as "barriers" to nuclear reprogramming and epigenetic deregulation often observed in many cancers.
Lorenz, D.R., Mikheyeva, I.V., Johansen, P., Meyer, L., Berg, A., Grewal, S.I., Cam. H.P. CENP-B cooperates with Set1 in bidirectional transcriptional silencing and genome organization of retrotransposons. Mol. Cell. Biol. 32: 4215-4225 (2012).
Cam, H.P. Roles of RNAi in chromatin regulation and epigenetic inheritance. Epigenomics 2: 613-626 (2010).
Cam, H.P., Chen, E.S., Grewal, S.I. 2009. Transcriptional scaffolds for heterochromatin assembly. Cell 136: 610–614.
Chen, E.S., Zhang, K., Nicolas, E., Cam, H.P., Zofall, M., Grewal, S.I. 2008. Cell cycle control of centromeric repeat transcription and heterochromatin assembly. Nature 451: 734–737.
Cam, H.P., Noma, K., Ebina, H., Levin, H.L., Grewal, S.I. 2008. Host genome surveillance for retrotransposons by transposon-derived proteins. Nature 451: 431–436.
Cromie, G., Randy, W.P., Cam, H., Farah, J.A., Grewal, S.I., Smith, G.R. 2007. A discrete class of intergenic DNA dictates meiotic DNA break hotspots in fission yeast. PLoS Genetics 3: 1496–1507.
Nicolas, E., Yamada, T., Cam, H.P., Fitzgerald, P.C, Kobayashi, R., Grewal, S.I. 2007. Distinct roles of HDAC complexes in promoter silencing, antisense suppression and DNA damage protection. Nature Structural & Molecular Biology 14: 372–380.
Sugiyama, T., Cam, H.P., Sugiyama R., Noma, K., Zofall, M., Kobayashi, R., Grewal, S.I. 2007. SHREC, an effector complex for heterochromatic transcriptional silencing. Cell 128: 491–504.
Noma, K., Cam, H.P., Maraia, R.J., Grewal, S.I. 2006. A role for TFIIIC transcription factor complex in genome organization. Cell 125: 859–872.
Cam, H.P., Sugiyama, T., Chen, E.S., Chen, X., Fitzgerald, P.C., Grewal, S.I. 2005. Comprehensive analysis of heterochromatin- and RNAi-mediated epigenetic control of the fission yeast genome. Nature Genetics 37: 809–819.
Sugiyama, T., Cam, H., Verdel, A., Moazed, D., Grewal, S.I. 2005. RNA-dependent RNA polymerase is an essential component of a self-enforcing loop coupling heterochromatin assembly to siRNA production. Proceedings of the National Academy of Sciences of the USA 102: 152–157.
Cam, H., Balciunaite, E., Blais, A., Spektor, A., Scarpulla, R.C., Young, R., Kluger, Y., Dynlacht, B.D. 2004. A common set of gene regulatory networks links metabolism and growth inhibition. Molecular Cell 16: 399–411.