Faculty / Research

Christopher Brownlee, PhD

Assistant Professor  440 Centers for Molecular Medicine
631-632-1593  Christopher.Brownlee@stonybrook.edu
Molecular mechanisms of spindle orientation, ciologenesis, polarity, cytokinesis and axonogenesis.

The Brownlee laboratory explores the interaction between two fundamental domains of the
cell: the plasma membrane and the cytoplasm. The lab’s interdisciplinary approach leverages
the powerful Xenopus system in which cytoplasmic extracts prepared from unfertilized frog
eggs can reconstitute various cellular processes, such as nuclear and mitotic spindle formation
and function, in vitro. To study the interaction between the plasma membrane and cytoplasm
as a function of cell size, we have adapted a method of encapsulating DNA-containing
cytoplasm in various lipid mixtures using microfluidics. This unique approach published recently
(Brownlee and Heald, Cell. 2019), has allowed for the discovery of a novel sensing mechanism
of the cellular surface area to volume ratio to regulate organelle size scaling. This pathway is
conserved in vivo during frog development as well as in human cells. This is particularly relevant
to our understanding of cancer pathology as loss of certain tumor suppressors or
overexpression of oncogenes frequently results in organelle size deregulation and can be used
diagnostically.

 

                       

                 Xenopus laevis                                  cell-like droplets encapsulating mitotic spindles

Current research utilizes microfluidic approaches while also employing the spatial-temporal
control obtained through the use of optogenetics. This research will provide new insight into
the underlying principles regulating such fundamental processes as mitotic spindle positioning,
cell polarity determination, ciliogenesis, axonogenesis and actin cortex formation. These processes
are essential for development and viability and defective in many human diseases such as cancer.

 

              

    Ciliogenesis                  Polarity                     Actin Cortex              Axonogenesis        Spindle positioning

Chris developed an interest in applying genetic and biochemical approaches to fundamental cell
biology questions as a graduate student in Gregory Roger’s lab at the University of Arizona
College of Medicine, culminating in a doctorate in the area of Cellular and Molecular Medicine.
As an NSF Graduate Research Fellow, he sought to answer the question of how a single
“mother” centriole gives birth to a single “daughter” centriole only once per cell cycle. Using
Drosphila and human cell culture, he studied how this process can be corrupted, contributing to
chromosome mis-segregation and tumorigenesis. He identified a phosphatase, PP2A-Twins,
which is integral in maintaining the careful balance of phosphorylation and dephosphorylation
of the master regulator of centriole duplication, the kinase Plk4. This work also identified the
mechanism by which a tumorigenic virus, SV40, subverts this pathway leading to centriole
amplification and tumorigenesis. In his postdoctoral research, within the lab of Rebecca Heald
at the University of California – Berkeley, he studied the mechanisms by which cells regulate
organelle size scaling using Xenopus and human cell culture. This research was supported by an
American Cancer Society Fellowship and led to Chris receiving the MCB Postdoctoral Award for
Research in 2018. Chris decided to join the faculty at the Stony Brook University School of Medicine 2019.

2020

Miller, K. E., Brownlee, C.W., & Heald, R. The power of amphibians to elucidate mechanisms of size control and scaling. Experimental Cell Research. 2020, July 1. DOI: 10.1016/J.YEXCR.2020.112036.

2019

Brownlee, C.W., Heald, R. Importin α partitioning to the plasma membrane regulates intracellular scaling. Cell. February 7, 2019. DOI: 10.1016/j.cell.2018.12.001.

2018

Brownlee, C.W., Heald, R. The Incredible Shrinking Spindle. Developmental Cell. 2018, May 21. DOI: 10.1016/j.devcel.2018.05.007.

Tiffany A. McLamarrah, Daniel W. Buster, Brian J. Galletta, Cody J. Boese, John M. Ryniawec, Natalie Ann Hollingsworth,  Amy E. Byrnes, Brownlee, C.W., Kevin C. Slep, Nasser M. Rusan, Gregory C. Rogers. An ordered pattern of Ana2 phosphorylation by Plk4 is required for centriole assembly. The Journal of Cell Biology.  2018, March 1. DOI: 10.1083/jcb.201605106.

2014

Galletta, B. J., Guillen, R. X., Fagerstrom, C. J., Brownlee, C. W., Lerit, D. a, Megraw, T. L., Rogers, G.C. Rusan, N. M. Drosophila Pericentrin requires interaction with Calmodulin for its function at centrosomes and neuronal basal bodies, but not at sperm basal bodies. Molecular Biology of the Cell. 2014, September 15. DOI:10.1091/mbc.E13-10-0617.

2012

Brownlee C.W., Rogers GC. Show me your license, please: deregulation of centriole du-plication mechanisms that promote amplification. Cell Mol Life Sci. 2012, Aug 15. DOI: 10.1007/s00018-012-1102-6.

2011

Brownlee C.W., Klebba JE, Buster DW, Rogers GC. The Protein Phosphatase 2A regulatory subunit Twins stabilizes Plk4 to induce centriole amplification. The Journal of Cell Biology. 2011, October 10. DOI: 10.1083/jcb.201107086.