faculty photo

Ben E. Black

Eldridge Reeves Johnson Foundation Professor of Biochemistry and Biophysics
Department: Biochemistry and Biophysics

Contact information
913A Stellar-Chance Laboratories
Philadelphia, PA 19104
Office: 215-898-5039
Fax: 215-573-7058
Education:
B.A. (Biology)
Carleton College, 1997.
PhD (Biochemistry and Molecular Genetics)
University of Virginia, 2002.
Post-Graduate Training
Postdoctoral Fellow, Ludwig Institute for Cancer Research; University of California, San Diego, 2002-2006.
Permanent link
 
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Description of Research Expertise

Description of Research:
The longest standing goal of my lab has been to understand how particular proteins direct accurate chromosome segregation at mitosis and meiosis. In humans, the chromosomal element—the centromere—that directs this process is not defined by a particular DNA sequence. Rather, the location of the centromere is dictated by an epigenetic mark generated by one or more resident proteins. These centromeric proteins interact directly with the DNA to create a specialized chromatin compartment that is distinct from any other part of the chromosome. By taking biophysical, biochemical, genetic, epigenomic, and cell biological approaches, our work is to define the composition and physical characteristics of the protein and protein/DNA complexes that epigenetically mark the location of the centromere on the chromosome. This work involves building centromeric chromatin from its component parts for analysis of its physical characteristics, developing biochemical assays to reconstitute steps in the process of establishing and maintaining the epigenetic mark, exploiting emerging genomic and epigenomic technologies to investigate the structure of centromeric chromatin, and using cell and organismal approaches to study the behavior of proteins involved in centromere inheritance and other essential aspects related to chromosome segregation at cell division. We are using the understanding gained from this work to advance technologies for building synthetic chromosomes for applications in research and medicine. An exciting new area of interest for my group to emerge in the last several years has been with the enzyme PARP-1: a key component for signaling DNA damage and an important clinical target for small molecule inhibition. Our work with PARP-1 has defined the allosteric network that potently activates the enzyme upon binding to a DNA break. Most recently, we have discovered that clinical PARP inhibitor (PARPi) compounds fall into three distinct types, depending on their allosteric modulation of DNA binding affinity. Our collaborative team is using this understanding to develop ‘designer’ PARPi compounds where the allosteric effects they confer are tuned for either strong DNA retention (i.e. potent for cancer cell killing) or strong DNA release (i.e. for inhibiting PARP-1 activity in neuroinflammatory and cardiovascular disease where preserving cell viability is the goal).

Lab personnel:
Praveen Allu - Postdoctoral Researcher
Ramya Billur - Postdoctoral Researcher
Nikaela Bryan - Ph.D. Student, BMB
Arunika Das - Postdoctoral Researcher (co-mentored by Mike Lampson)
Jennine Dawicki-McKenna - Senior Research Investigator
Craig Gambogi - Ph.D. Student, BMB
Viridiana Herrera - Postdoctoral Researcher
Nick John - Research Specialist
Katie Kixmoeller - MD/Ph.D. Student
Nootan Pandey - Postdoctoral Researcher
Ye Yang - Postdoctoral Researcher (co-mentored by Mike Lampson)
Qiupeng Zheng - Postdoctoral Researcher

Selected Publications

Zandarashvili, L., Langelier, M.F., Velagapudi, U.K., Hancock, M.A., Steffen, J.D., Billur, R., Hannan, Z.M., Wicks, A.J., Krastev, D.B., Pettitt, S.J., Lord, C.J., Talele, T.T., Pascal, J.M., Black, B.E.: Structural basis for allosteric PARP-1 retention on DNA breaks. Science 368: eaax6367, 2020 Notes: Zandarashvili (Black Lab) and Langelier are co-first authors. Pascal and Black are co-corresponding authors.

Allu, P.K., Dawicki-McKenna, J.M., Van Eeuwen, T., Slavin, M., Braitbard, M., Xu, C., Kalisman, N., Murakami, K., Black, B.E.: Structure of the human core centromeric nucleosome complex. Current Biology 29: 2625-2639, 2019.

Logsdon, G.L., Gambogi, C.W., Liskovykh, M.A., Barrey, E.J., Larionov, V., Miga, K.H., Heun, P., Black, B.E.: Human artificial chromosomes that bypass centromeric DNA. Cell 178: 624-639, 2019.

Iwata-Otsubo, A., Dawicki-McKenna, J.M., Akera, T., Falk, S.J., Chmatal, L., Yang, K., Sullivan, B.A., Schultz, R.M., Lampson, M.A., Black, B.E.: Expanded satellite repeats amplify a discrete CENP-A nucleosome assembly site on chromosomes that drive in female meiosis. Current Biology 27: 2365-2373, 2017 Notes: Iwata-Otsubo and Dawicki-McKenna (Black Lab) are co-first authors. Lampson and Black are co-corresponding authors.

Guo, L.Y., Allu, P.K., Zandarashvili, L., McKinley, K.L., Sekulic, N., Dawicki-McKenna, J.M., Fachinetti, D., Logsdon, G.A., Jamiolkowski, R., Cleveland, D.W., Cheeseman, I.M., Black, B.E.: Centromeres are maintained by fastening CENP-A to DNA and directing an arginine anchor-dependent nucleosome transition. Nature Communications 8: 15775, 2017.

Falk, S.J., Guo, L.Y., Sekulic, N., Smoak, E.M., Mani, T., Logsdon, G.A., Gupta, K., Jansen, L.E.T., Van Duyne, G.D., Vinogradov, S.A., Lampson, M.A., Black, B.E.: CENP-C reshapes and stabilizes CENP-A nucleosomes at the centromere. Science 348: 699-703, 2015 Notes: Falk (Black Lab), Guo (Black Lab), Sekulic (Black Lab), and Smoak (Black/Lampson Labs) are co-first authors.

Hasson, D., Panchenko, T., Salimian, K.J., Salman, M.U., Sekulic, N., Alonso, A., Warburton, P.E., Black, B.E.: The octamer is the major form of CENP-A nucleosomes at human centromeres. Nature Structural & Molecular Biology 20: 687-695, 2013 Notes: Hasson, Panchenko (Black Lab), and Salimian (Black Lab) are co-first authors.

Salimian, K.J., Ballister, E.R., Smoak, E.M., Wood, S., Panchenko, T., Lampson, M.A., Black, B.E.: Feedback control in sensing chromosome biorientation by the Aurora B kinase. Current Biology 21: 1158-1165, July 2011 Notes: Lampson and Black are co-corresponding authors.

Black, B.E., Cleveland, D.W.: Epigenetic centromere propagation and the nature of CENP-A nucleosomes. Cell 144: 471-479, Feb 2011 Notes: Black and Cleveland are co-corresponding authors.

Sekulic, N., Bassett, E.A., Rogers, D.J., Black, B.E.: The structure of (CENP-A/H4)(2) reveals physical features that mark centromeres. Nature 467: 347-351, September 2010.

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Last updated: 04/29/2020
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