Morgan Sammons

Sammons Lab
 

Areas of Interest

• Genomics and systems biology of the p53 transcriptional network
• Epigenetic and genetic variation in the p53 tumor suppressor response
• The TP53 family in development and human disease
• Chromatin biology and trancriptional enhancers

Research

The goal of the Sammons Laboratory is to advance a mechanistic understanding of p53 activity within variable genetic and epigenetic contexts. TP53 is the most frequently mutated gene in human cancer and genetic evidence across biological taxa implicates TP53 as a master tumor suppressor gene. The p53 protein is a DNA-binding transcription factor that responds to diverse intrinsic and extrinsic cellular stress signals by activating an anti-oncogenic gene expression program. Despite the critical nature of the p53 protein in tumor suppression, the mechanisms by which p53 elicits these cell-protective gene expression cascades are not well understood.

The lab is currently interested in two fundamental questions pertaining to the activity of p53 family member proteins. First, we are investigating how wild-type p53 exerts tumor suppressor activity in the context of genomic and epigenomic variability. Simply put, we want to better understand how p53 interacts with and functions on chromatin, the physiological template of DNA. Second, we are interested in elucidating the mechanisms underlying p53-dependent and cell lineage-specific tumor suppression. That is, why and how does p53 behave differently across different cells, tissues and organisms. Finally, the lab is fascinated with how the p53 family members p63 and p73 elicit radically different cellular responses, despite interacting with the same DNA sequences.

Our work on p53 spans multiple experimental paradigms, from traditional molecular and biochemical techniques to cutting-edge genetic and genomic technologies. We are currently recruiting excited and motivated undergraduate, graduate, and post-doctoral trainees to join the laboratory.

Publications

• Capell, B.C., Drake, A.M., Zhu, J., Shah, P.P., Dou, Z., Dorsey, J., Simola, D.F., Donahue, G., Sammons, M.A, Singh Rai, R., Natale, C., Ridky, T.W., Adams, P.D., and Berger, S.L. (2016). MLL1 is essential for the senescence-associated secretory pehotype Genes and Development, 30: 321-336
• Sammons, M.A., Zhu, J., Drake, A.M., and Berger, S.L. (2015). TP53 engagement with the genome occurs in distinct local chromatin environments via pioneer factor activity. Genome Research 25, 179-188.
• Zhu, J, Sammons, M.A, Donahue, G, Dou, Z, Vedadi, M, Geglik, M, Barsyte-Lovejoy, D, Al-Awar, R, Katona, B, Shilatifard, A, Huang, J, Hua, X, Arrowsmith, C, and Berger, S.L. (2015) Gain-of-function p53 mutants co-opt chromatin pathways to drive cancer growth. Nature, 525 (7568):206-11
• Dikovskaya, D, Cole J.J., Mason S.M., Nixon, C, Karim, S.A., McGarry, L, Clarke, W, Hewitt, R.N., Sammons, M.A, Zhu, J, Wu, H, Berger, S.L., Blyth, K, and Adams, P.D. (2015) Mitotic stress is an integral part of the oncogene-induced senescence program that promotes multinucleation and cell cycle arrest. Cell Reports. 12(9):1483-96
• Mushrush, D.J., Koteiche, H.A., Sammons, M.A., Link, A.J., McHaourab, H.S., and Lacy, D.B. (2011). Studies of the mechanistic details of the pH-dependent association of botulinum neurotoxin with membranes. J Biol Chem 286, 27011-27018.
• Sammons, M.A., Samir, P., and Link, A.J. (2011). Saccharomyces cerevisiae Gis2 interacts with the translation machinery and is orthogonal to myotonic dystrophy type 2 protein ZNF9. Biochem Biophys Res Commun 406, 13-19.
• Sammons, M.A., Antons, A.K., Bendjennat, M., Udd, B., Krahe, R., and Link, A.J. (2010). ZNF9 activation of IRES-mediated translation of the human ODC mRNA is decreased in myotonic dystrophy type 2. PLoS One 5, e9301.
• Elzie, C.A., Colby, J., Sammons, M.A., and Janetopoulos, C. (2009). Dynamic localization of G proteins in Dictyostelium discoideum. J Cell Sci 122, 2597-2603.
• Sammons, M., Wan, S.S., Vogel, N.L., Mientjes, E.J., Grosveld, G., and Ashburner, B.P. (2006). Negative regulation of the RelA/p65 transactivation function by the product of the DEK proto-oncogene. J Biol Chem 281, 26802-26812.