Nasser M. Rusan, Ph.D.
Laboratory of Molecular Machines and Tissue Architecture
Building 50, Room 2120
50 South Drive
Bethesda, MD 20814
The Rusan Lab studies the role of centrosomes during animal development. The centrosome is a non-membrane bound organelle that serves as the main microtubule (MT) organizing center of most animal cells. Centrosomes function to initiate and maintain cell polarity, guide cell migration, direct intracellular cargos, and properly distribute other organelles. In mitosis, centrosomes are critical for accurate construction of the mitotic spindle to ensure faithful chromosome segregation to the two daughter cells. Thus, it is not a surprise that defects in centrosome function lead to a wide range of failures at the cellular level, which in turn, leads to tissue defects and many human diseases. The lab aims to determine how centrosomes are properly constructed from their individual parts and how centrosomes function in a wide range of cell types to avoid human diseases such as polycystic kidney disease, microcephaly, cancer and many others.
To study the centrosome, the Rusan Lab uses Drosophila genetics, cell biology, super-resolution microscopy, biochemistry, and modern molecular biology. Most recently, the lab undertook a targeted yeast-2-hybrid to define the direct protein-protein interaction (PPI) landscape of the centrosome. This centrosome ‘interactome’, in combination with the above mentioned techniques, is used to dig deep into the mechanisms of centrosome protein function. A general theme has emerged from these studies, that is, protein-protein network diversity is responsible for the diversity of centrosome functions across cell types and cell cycle stages. In other words, not all centrosomes are made equally. Understanding this centrosome PPI diversity is a priority because it could help explain why different mutations in centrosome proteins affect specific cell types and manifest different diseases.
The Rusan Lab’s current work focuses on two proteins, Pericentrin-Like-Protein (PLP) and Asterless (Asl), referred to as ‘linker’ proteins because they bridge the two main components of the centrosome – centrioles and the Pericentriolar Material (PCM). The centrosome interactome truly highlights how little is known about these two proteins. PLP and Asl interact with a large number of partners and the Rusan Lab is in the process of defining the role of each of these interactions with respect to short timescales (cell cycle) and long timescales (different developmental stages) in a variety of cell types. This work will shed light on how mutations in Pericentrin, the human ortholog of PLP, lead to microcephalic osteodysplastic primordal dwarfism type II (MOPD II).
Nasser Rusan moved to the U.S. from Jordan in 1996. He graduated from the University of Massachusetts with a B.S. in molecular biology in 2000 and a Ph.D. in molecular and cellular biology in 2005. He conducted postdoctoral research at the University of North Carolina Chapel Hill from 2005-2011. He was awarded an American Cancer Society Postdoctoral fellowship in 2006, and received the University of North Carolina Postdoctoral Award for Research Excellence in 2009. Dr. Rusan joined the NHLBI in 2011 as an Earl Stadtman tenure-track Investigator. He is a member of the American Society for Cell Biology and serves on the editorial boards of Frontiers in Developmental and Cell Biology and Molecular Biology of the Cell (MBoC).
Galletta BJ, Fagerstrom CJ, Schoborg TA, McLamarrah TA, Ryniawec JM, Buster DW, Slep KC, Rogers GC, Rusan NM. A centrosome interactome provides insight into organelle assembly and reveals a non-duplication role for Plk4. Nat Commun. 2016;7:12476.
Galletta BJ, Jacobs KC, Fagerstrom CJ, Rusan NM. Asterless is required for centriole length control and sperm development. J Cell Biol. 2016;213(4):435-50.
Lerit DA, Rusan NM. PLP inhibits the activity of interphase centrosomes to ensure their proper segregation in stem cells. J Cell Biol. 2013;202(7):1013-22.
Schoborg T, Zajac AL, Fagerstrom CJ, Guillen RX, Rusan NM. An Asp-CaM complex is required for centrosome-pole cohesion and centrosome inheritance in neural stem cells. J Cell Biol. 2015;211(5):987-98.
Lerit DA, Jordan HA, Poulton JS, Fagerstrom CJ, Galletta BJ, Peifer M, Rusan NM. Interphase centrosome organization by the PLP-Cnn scaffold is required for centrosome function. J Cell Biol. 2015;210(1):79-97.
Related Scientific Focus Areas
Genetics and Genomics
This page was last updated on August 17th, 2016