Fusun Kilic, Ph.D.

Assistant Professor 

Associate Research Scientist at Yale University
NARSAD and AHA Postdoctoral Fellow, Yale University
Ph.D., University of Western Ontario
B.S., Bogazici University (Formerly known as Robert College)

Serotonin and serotonin transporter protein. 

The projects in my laboratories are focused on the relationship between serotonin (5HT) and the serotonin transporter (SERT) during health and disease stages.

5HT is a platelet-stored vasoconstrictor that also acts as a neurotransmitter and a developmental signal early in embryogenesis. Alterations in the levels of 5HT (i) in the nervous system are associated with a number of neuropsychiatric disorders; (ii) in blood plasma are associated with major heart and kidney diseases; (iii) in placenta causes maternal and prenatal morbidity and mortality via mediating high blood pressure, and neuroanatomical abnormalities. SERT on the membranes of trophoblast cells regulates extracellular 5HT levels and prevents vasoconstriction in the placental vascular bed, thereby securing a stable blood flow to the embryo. Also, the initial 5HT is derived from the maternal-embryonic circulation via placental SERT. Although neurons producing 5HT are among the first to develop in the mammalian central nervous system, the biosynthesis of 5HT within the embryo occurs after the serotonergic neurons are first detectable. The actions of 5HT are mediated by different types of receptors and terminated by a single transporter, SERT. Therefore, SERT plays a major role during health and disease stages.

The regulatory roles of substrates and inhibitors on their transporters are well established. However, the mechanism by which 5HT regulates SERT has remained elusive. The overall goal of our research projects is to explore the underlying mechanism by which exogenous 5HT regulates the structure and function of SERT.

Selected Publications

Ahmed, BA., Jeffus, B., Bukhari, IS., Harney, JT., Unal, R., Lupashin, VV.,  van der Sluijs, P., and Kilic, F. "Serotonin Transamidates Rab4 and Facilitates Its Binding to the C-Terminus of SERT." 2008 J. Biol. Chem (in press). [Abstract]

Brenner, B., Harney, JT., Ahmed, BA., Jeffus, BC., Unal, R., Mehta J.L., and Kilic, F. "Plasma serotonin level and the platelet serotonin transporter." 2007. J. Neurochem. 102(1):206-15 [Abstract]

Unal, R., Ahmed, BA., Jeffus, BA., Harney, J.T., Lyle, CS., Wu, Y-K. Chambers, TC., Reece, EA, and Kilic, F. "At diabetes-like concentration, glucose down-regulates the placental serotonin transport system by abolishing its homo-oligomerization." 2006 J. Neurochem. 101, 937-948 [Abstract]

Ozaslan D, Wang S, Ahmed BA, Kocabas AM, McCastlain JC, Bene A, Kilic F. Glycosyl modification facilitates homo- and hetero-oligomerization of the serotonin transporter. A specific role for sialic acid residues. J Biol Chem. 2003 278(45):43991-4000. [Abstract]

 Kocabas AM, Rudnick G, Kilic F. Functional consequences of homo- but not hetero-oligomerization between transporters for the biogenic amine neurotransmitters. J Neurochem. 2003 85(6):1513-20. [Abstract]

Kilic F., Murphy DL., Rudnick G. A human serotonin transporter mutation causes constitutive activation of transport activity. Mol Pharmacol. 2003 64(2):440-6. [Abstract]

Kilic F., Rudnick G. Oligomerization of serotonin transporter and its functional consequences. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3106-11. [Abstract]

Kilic F., Johnson DA., Sinensky M.  Subcellular localization and partial purification of prelamin A endoprotease: an enzyme which catalyzes the conversion of farnesylated prelamin A to mature lamin A. FEBS Lett. 1999 30;450(1-2):61-5. [Abstract]

Kilic F., Salas-Marco J, Garland J, Sinensky M. Regulation of prelamin A endoprotease activity by prelamin A. FEBS Lett. 1997 414(1):65-8. [Abstract]

Kilic F., Dalton MB, Burrell SK, Mayer JP, Patterson SD, Sinensky M. In vitro assay and characterization of the farnesylation-dependent prelamin A endoprotease. J Biol Chem. 1997 272(8):5298-304. [Abstract]