Leo Tsiokas

Professor, Department of Cell Biology
John S. Gammill Endowed Chair in Polycystic Kidney Disease, Warren Medical Research Institute  

EDUCATION 

B.S., Pharmacy, Aristotle University, Greece 
Ph.D., Pharmacology, University of Medicine and Dentistry, New Jersey



RESEARCH SUMMARY

Project 1: Molecular and cellular basis of Autosomal Dominant Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic diseases affecting more than half a million Americans and 12.5 million people, worldwide. Mutations in two genes, PKD1 and PKD2 are responsible for ADPKD. Their protein products, originally called PKD1 and PKD2 or polycystin-1 and 2 (currently named, TRPP2), respectively, are plasma membrane-spanning proteins. It has been speculated that PKD1 and TRPP2 assemble into a receptor-channel complex linking extracellular stimuli to Ca2+ signaling. However, there are three major, yet unresolved questions that form the focus of our research interests: 1) What is the nature of the extracellular stimuli that activate the PKD1/TRPP2 receptor/channel complex? 2) How activation of PKD1 leads to the activation of TRPP2? 3) What are the downstream effectors of the PKD1/TRPP2 complex? These questions are being investigated using complementary approaches in cell culture and the mouse. 

Project 2: Role of primary cilia in cell division and development

Primary cilia are sensory, antenna-like organelles, present in virtually every cell type of the human body. Polycystic kidney disease, retinal degeneration, hydrocephalus, exencephaly, situs inversus, polydactyly, defects in skeletal and neural tube patterning, and cancer form only a partial list of pathological conditions associated with the primary cilium. A unique feature of the primary cilium is its ability to oscillate out of phase with the cell cycle, as primary cilia are formed when cells exit the cell cycle, whereas they are disassembled upon entry into the cell cycle. This feature enables cilia to coordinate multiple signaling pathways with the cell cycle. Cilia reach a defined length in G1/G0 and structural defects that cause abnormally short or long cilia have dire consequences in cells and organisms. My laboratory is interested in the mechanisms coordinating cilium biogenesis and length control with the cell cycle. 

Project 3: Ca2+ signaling in osteoclasts  

Osteoclasts are constantly made throughout life from hematopoietic stem cells residing in the bone marrow through a series of complex events involving cytokine signaling and the microenvironment. Ca2+ signaling has an essential role in the regulation of osteoclastogenesis. Ca2+ channels activated in response to the depletion of intracellular Ca2+ stores have been suggested to mediate Ca2+ signaling in early stages of osteoclast formation. However, the exact molecules and mechanism(s) by which these channels control Ca2+ signaling are largely unknown. Using a combination of molecular, cell biological and whole animal studies, we have been investigating the role of the Transient Receptor Potential channel 1 (TRPC1) in this process.

 

SELECTED PUBLICATIONS:

1. Kim S, Nie H, Nesin V, Tran U, Outeda P, Bai CX, Keeling J, Maskey D, Watnick T, Wessely O, Tsiokas L. The polycystin complex mediates Wnt/Ca2+ signaling. Nature Cell Biology, 18(7):752-64, 2016.

http://www.nature.com/nrneph/journal/v12/n7/pdf/nrneph.2016.77.pdf

http://f1000.com/prime/726375187

2. Keeling J., Tsiokas L., and Maskey D. Cellular mechanisms of ciliary length control. Cells, 5(1):6-25, 2016. Review article

3. Maskey D., Marlin MC, Kim S, Kim S, Ong EC, Li G, and Tsiokas L. Cell cycle-dependent ubiquitylation and destruction of NDE1 by CDK5-FBW7 regulates ciliary length. EMBO Journal, 34(19):2424-40,2015                                                                                                                               
"News and Views:" http://emboj.embopress.org/content/embojnl/34/19/2388.full.pdf

4. Nesin V, Wiley G, Kousi M, Ong EC, Lehmann T, Nicholl DJ, Suri M, Shahrizaila N, Katsanis N, Gaffney PM, Wierenga KJ, Tsiokas L. Activating mutations in STIM1 and ORAI1 cause overlapping syndromes of tubular myopathy and congenital miosis. Proceedings of the National Academy of Sciences (USA), 111(11):4197-202, 2014.

5. Ong EC, Nesin V, Long CL, Bai CX, Guz JL, Ivanov IP, Abramowitz J, Birnbaumer L, Humphrey MB, Tsiokas L. A TRPC1 Protein-dependent Pathway Regulates Osteoclast Formation and Function. Journal of Biological Chemistry, 288(31): 22219-32, 2013

6. Kim S., Zaghloul NA., Bubenshchikova E., Oh EC., Rankin S., Katsanis N., Obara T., and Tsiokas L. Nde-1 mediated suppression of ciliogenesis affects cell cycle re-entry. Nature Cell Biology, 13(4): 351-60, 2011.
“New and Views:”    http://www.nature.com/ncb/journal/v13/n4/pdf/ncb0411-340.pdf

7. Bai CX., Kim S., Li WP., Streets AJ., Ong AC., and Tsiokas L. Activation of TRPP2 through mDia1-dependent voltage gating. EMBO Journal, 27: 1345-1356, 2008.

8. Ma, R., Li, W. P., Rundle, D., Kong, J., Akbarali, H., and Tsiokas, L. PKD2 functions as an Epidermal Growth Factor-activated plasma membrane channel. Molecular and Cellular Biology 25(18): 8285-98, 2005.

featured article at Science’s STKE: (http://stke.sciencemag.org/cgi/content/abstract/sigtrans;2005/301/tw327?fulltext=tsiokas&searchid=QID_NOT_SET




MAILING ADDRESS

University of Oklahoma Health Sciences Center 
Stanton L. Young Biomedical Research Center 
Room 262A 
975 NE 10th Ave
Oklahoma City, OK 73104
Phone: (405) 271-8001 ext. 46211 
Fax: (405) 271-3548 

Leonidas-Tsiokas@ouhsc.edu

CV - Leonidas Tsiokas, Ph.D.