Brian David Dynlacht

Biosketch / Results /

Brian Dynlacht

Professor, Department of Pathology
Scientific Director -Genomics Facility

Contact Info

Address
522 First Avenue
New York, NY 10016

212/263-6162
Brian.Dynlacht@nyumc.org


Education

1992 — Univ of Calif Berkeley, Medical Education

Research Summary

Our research program has taken advantage of multiple, complementary approaches, each aimed at understanding the mechanisms underlying progression through the mammalian cell cycle. In particular, we have chosen to focus on transcriptional mechanisms that link gene expression with cell cycle progression.
These studies have largely centered on the retinoblastoma tumor suppressor protein, pRB, and the related proteins p107 and p130. pRB is a prototypical tumor suppressor known to be mutated in many human tumors. pRB and its relatives restrain cell growth by inhibiting the activity of a cellular transcription factor, E2F, that controls the expression of key components of the cell cycle and DNA replication machinery. Using a combination of biochemistry, cell biology, and mutant cell lines, we are attempting to understand how critical gene targets are regulated by E2F and pRB. We have combined the use of a technique known as chromatin immunoprecipitation (ChIP) with a genomic approach employing DNA microarray analysis in order to begin understanding how gene regulatory networks are controlled during the cell cycle and differentiation in living mammalian cells. The pRB family controls a number of developmental decisions as well as cell cycle arrest in response to DNA damage. We hope to uncover novel targets of pRB that reveal a regulatory pathway of biologically relevant, functional interactions that drive cells toward each of these fates.
In addition to studies aimed at addressing transcriptional control of the cell cycle, we are also focusing on understanding another event linked to the cell cycle, namely duplication of centrosomes. The centrosome, involved in organizing the mitotic spindle, is poorly understood, although it was first observed 100 years ago. We have identified a novel protein, CP110, that may link the duplication of this organelle to the cell cycle. Since genomic instability ensues when CP110 is mutated, we are investigating potential links between this protein and human cancer.

Supplementary figures for Balciunaite et. al., MCB, 2005.

Cilium assembly and disassembly
Sanchez, Irma; Dynlacht, Brian David. Cilium assembly and disassembly. Nature cell biology. 2016 Jun;18(7):711-717 (2165552)

Tethering of an E3 ligase by PCM1 regulates the abundance of centrosomal KIAA0586/Talpid3 and promotes ciliogenesis
Wang, Lei; Lee, Kwanwoo; Malonis, Ryan; Sanchez, Irma; Dynlacht, Brian D. Tethering of an E3 ligase by PCM1 regulates the abundance of centrosomal KIAA0586/Talpid3 and promotes ciliogenesis. eLife. 2016 May 5;5:?-? (2100872)

PAF Complex Plays Novel Subunit-Specific Roles in Alternative Cleavage and Polyadenylation
Yang, Yan; Li, Wencheng; Hoque, Mainul; Hou, Liming; Shen, Steven; Tian, Bin; Dynlacht, Brian D. PAF Complex Plays Novel Subunit-Specific Roles in Alternative Cleavage and Polyadenylation. PLoS genetics. 2016 Jan 14;12(1):e1005794-e1005794 e1005794 (1921242)

Nek2 activation of Kif24 ensures cilium disassembly during the cell cycle
Kim, Sehyun; Lee, Kwanwoo; Choi, Jung-Hwan; Ringstad, Niels; Dynlacht, Brian David. Nek2 activation of Kif24 ensures cilium disassembly during the cell cycle. Nature communications. 2015 Aug 20;6:8087-8087 (1732382)

The Microtubule-Depolymerizing Activity of a Mitotic Kinesin Protein KIF2A Drives Primary Cilia Disassembly Coupled with Cell Proliferation
Miyamoto, Tatsuo; Hosoba, Kosuke; Ochiai, Hiroshi; Royba, Ekaterina; Izumi, Hideki; Sakuma, Tetsushi; Yamamoto, Takashi; Dynlacht, Brian David; Matsuura, Shinya. The Microtubule-Depolymerizing Activity of a Mitotic Kinesin Protein KIF2A Drives Primary Cilia Disassembly Coupled with Cell Proliferation. Cell reports. 2015 Feb 4;:?-? (1462452)