Saul Siller
Education:
B.A. Vanderbilt University, Nashville, TN (2011)
Current Position:
8th Year MSTP
4th Year Medical Student
Advisor:
Dr. Ken-Ichi Takemaru, Ph.D.
Graduate Program:
Molecular and Cellular Pharmacology
Research Interest:
Multicilia are microtubule-based cellular projections that provide the motive force to propel mucus and debris out of our airways, cerebrospinal fluid in our nervous system, and the ovum in the female reproductive tract. Dysfunctional multicilia have been linked to genetic disorders, such as primary ciliary dyskinesia and cystic fibrosis, and been implicated in the pathogenesis of chronic respiratory diseases, including emphysema, chronic obstructive pulmonary disorder, and asthma. While multicilia play an absolutely essential role in human health, very little is known about how multicilia form and function. However, work from primary cilia, which are responsible for cellular signaling, as well as mutation analysis from human patients, have shown that a structure at the base of cilia termed the transition fiber (or distal appendage) is important. Therefore, to gain greater insight into the function of the transition fiber, we utilized two unique mouse knockout models where expression of the two transition fiber proteins Chibby1 and CEP164 was lost. We employed various imaging modalities, including super-resolution and electron microscopy, tissue histology, and primary cell culture techniques to interrogate the function of Chibby1 and CEP164 in different stages of multicilia formation. Interestingly, we demonstrated that Chibby1 regulates intraflagellar transport, a process responsible for building and maintaining ciliary axonemes. Additionally, this work determined that CEP164 is necessary for mammalian development and multiciliogenesis through the generation and characterization of a novel mouse model. Through this novel mouse model, we extended the role of CEP164 in basal body docking and ciliary vesicle formation to multicilia formation; however, we also revealed intriguing differences in CEP164 function in primary and multiciliogenesis. In particular, CEP164 limited the types of cellular membranes and associated membrane proteins that compose multicilia. These findings provided increased understanding into the physiological functions of the transition fiber and shed light on how proteins localizing to this critical structure function to build multicilia.
Publications:
Siller SS, Sharma H, Li S, Yang J, Zhang Y, Holtzman MJ, Winuthayanon W, Colognato H, Holdener BC, Li F-Q, Takemaru K-I (2017). “Conditional Knockout 1 Mice for the Distal Appendage Protein CEP164 Reveal Its Essential Roles in Airway Multiciliated Cell Differentiation.” PLoS Genet 13 (12):e1007128.
Li F-Q,* Chen X,* Fisher C, Siller SS, Zelikman K, Kuriyama R, Takemaru K-I (2016). "BAR Domain-Containing FAM92 Proteins Interact with Chibby1 to Facilitate Ciliogenesis." Mol Cell Biol 36 (21): 2668-2680. *Authors contributed equally to this work.
Nemajerova A, Kramer D,* Siller SS,* Herr C,* Shomroni O, Pena T, Suazo CG, Glaser K, Wildung MW, Steffen H, Sriraman A, Oberle F, Wienken M, Hennion M, Vidal R, Royen B, Alevra M, Schild D, Bals R, Dönitz J, Riedel D, Bonn S, Takemaru K-I, Moll UM, and Lizé M (2016). TAp73 is a central transcriptional regulator of airway multiciliogenesis. Genes & Development 30 (11): 1300-1312. *Authors contributed equally to this work. Featured article.
Li F-Q, Siller SS, and Takemaru K-I (2015). Basal body docking in airway ciliated cells. Oncotarget 6 (24): 19944-19945.
Siller SS,* Burke MC,* Li F-Q, and Takemaru K-I (2015). Chibby functions to preserve normal ciliary morphology through the regulation of intraflagellar transport in airway ciliated cells. Cell Cycle 14 (19): 3163-3172. *Authors contributed equally to this work.
Burke MC, Li F-Q, Cyge B, Arashiro T, Brechbuhl HM, Chen X, Siller SS, Weiss MA, O’Connell CB, Love D, Westlake CJ, Reynolds SD, Kuriyama R, and Takemaru K-I (2014). Chibby promotes ciliary vesicle formation and basal body docking during airway cell differentiation. J Cell Biol 207 (1): 123-137.
Siller SS and Broadie K (2012). Matrix Metalloproteinases and Minocycline: Therapeutic Avenues for Fragile X Syndrome. Neural Plasticity, vol. 2012, Article ID 124548, 9 pages, 2012. doi:10.1155/2012/124548
Siller SS and Broadie K (2011). Neural circuit architecture defects in a Drosophila model of Fragile X syndrome are alleviated by minocycline treatment and genetic removal of matrix metalloproteinase. Disease Models & Mechanisms 4(5): 673-685.
