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)

E-mailKilicFusun@uams.edu
Office:  (501)526-6488 – Biomedical Research Center B405D
Lab:  (501)686-5194 – Biomedical Research Center B410
FAX:  (501)686-8169

Serotonin and serotonin transporter.

Serotonin (5-HT) – a neurotransmitter, a vasoconstrictor compound that also acts as a mitogen, promotes cell division, mitosis, and a developmental signal early in embryogenesis.  The extracellular concentration of this multifunctional signaling molecule is associated with various diseases and must be regulated constantly by a single-gene product 5-HT transporter, SERT which is expressed on the plasma membrane of platelet, placenta and presynaptic terminals.  The 5-HT uptake capacity of the platelets depends on the number of SERT molecules on the plasma membrane.  Using a strategy of progressive integration, i.e., clinical (placentas, blood samples from term diabetic, episodic hypertensive and healthy/control subjects); and preclinical (peripheral 5-HT knock out TPH1-/-, SERT-/- and control mice), we explore to delineate the sequence of molecular events in the mechanism by which 5-HT- signaling facilitates the membrane trafficking, association with other proteins as well as post-translational modifications of SERT and how they are altered at pathophysiological conditions.

Please see our meeting announcement at: A new Keystone Meeting on Serotonin outside the brain:

http://www.keystonesymposia.org/17T5#utm_source=emaillink&utm_medium=banner&utm_campaign=T5email

Selected Publications

Lowery CL 3rd, Elliott C, Cooper A, Hadden C, Sonon RN, Azadi P, Williams DK, Marsh JD, Woulfe DS, Kilic F. Cigarette Smoking-Associated Alterations in Serotonin/ Adrenalin Signaling Pathways of Platelets. J. Am. Heart Assoc. 2017 18;6(5). pii: e005465. doi: 10.1161/JAHA.116.005465. https://www.ncbi.nlm.nih.gov/pubmed/28522678

Hadden C, Fahmi T, Cooper A, Savenka AV, Lupashin VV, Roberts DJ, Maroteaux L, Hauguel-de Mouzon S, Kilic F. Serotonin transporter protects the placental cells against apoptosis in caspase 3-independent pathway.  J. Cell Physiol. 2017 Jan 21. doi: 10.1002/jcp.25812 https://www.ncbi.nlm.nih.gov/pubmed/28109119

Joo JH, Wang B, Frankel E, Ge L, Xu L, Iyengar R, Li-Harms X, Wright C, Shaw TI, Lindsten T, Green DR, Peng J, Hendershot LM, Kilic F, Sze JY, Audhya A, Kundu M. The Noncanonical Role of ULK/ATG1 in ER-to-Golgi Trafficking Is Essential for Cellular Homeostasis. Mol. Cell. 2016. 62(6):982. doi: 10.1016/j.molcel.2016.05.030. https://www.ncbi.nlm.nih.gov/pubmed/27315557

Li Y, Cooper A, Odibo IN, Ahmed A, Murphy P, Koonce R, Dajani NK, Lowery CL, Roberts DJ, Maroteaux L, Kilic F. Discrepancy in insulin regulation between GDM-platelets and -placenta. J. Biol Chem. 2016. 291(18):9657-65. doi: 10.1074/jbc.M116.713693. PMID: 26921319https://www.ncbi.nlm.nih.gov/pubmed/26921319

Li Y, Hadden C, Cooper A, Ahmed A, Wu H, Lupashin VV, Mayeux PR, Kilic F. Sepsis-induced elevation in plasma serotonin facilitates endothelial hyperpermeability. Sci Rep. 2016. 6:22747. DOI: 10.1038/srep22747. https://www.ncbi.nlm.nih.gov/pubmed/26956613

Basnet, K., Bentley-Lewis, R., Wexler, D., Kilic, F., and Roberts, D.J. Intervillous thrombi are increased in placentas from pregnancies complicated by diabetes. Journal of Pregnancy & Child Health 2015. Dec 15.https://www.ncbi.nlm.nih.gov/pubmed/26669929

Li Y, Hadden C, Singh P, Mercado CP, Murphy P, Dajani NK, Lowery CL, Roberts DJ, Maroteaux L,Kilic F. GDM-associated insulin deficiency hinders the dissociation of SERT from ERp44 and down-regulates placental 5-HT uptake. Proc. Natl. Acad. Sci USA. 2014. 111(52):E5697-705. doi: 10.1073/pnas. https://www.ncbi.nlm.nih.gov/pubmed/25512553

Fraer M, Kilic F. Serotonin: A Different Player in Hypertension-Associated Thrombosis. Hypertension. 2015. Mar 9. pii: Hypertension-AHA.114.05061. [Abstract]

Ziu, E., Hadden, C., Li, Y., Lowery III, CL., Singh, P., Ucer, SS., Mercado, C., Gu, HH., Kilic, F. Effect of serotonin on platelet function in cocaine exposed blood.  Sci. Rep. 2014. 4, 5945. DOI: 10.1038/srep05945.  [Abstract]

Mercado CP, Quintero MV, Li Y, Singh P, Byrd AK, Talabnin K, Ishihara M, Azadi P, Rusch NJ, Kuberan B, Maroteaux L, Kilic F. A serotonin-induced N-glycan switch regulates platelet aggregation.  Sci. Rep. 2013 3, 2795. DOI: 10.1038/srep02795.  [Abstract]

Mercado CP., Byrum S., Beggs ML., Ziu E., Raj VR., Haun RS., Kilic F. Impact of Elevated Plasma Serotonin on Global Gene Expression of Murine Megakaryocytes PLoSONE, 2013. 8(8):e72580. PMID: 24013211.  [Abstract]

Freyaldenhoven, S., Li, Y., Kocabas, A.M., Ziu, E., Ucer, S., Ramanagoudr-Bhojappa, R., Miller, G.P., and Kilic, F. “The Role of ERp44 on the Maturation of Serotonin Transporter proteins. J. Biol. Chem. 2012. 287: 17801-17811. [Abstract]

Ziu, E., Freyaldenhoven, S., Mercado, C.P., Ahmed, B.A., Preeti, P., Lensing, S., Ware, J., and Kilic, F. Down-regulation of the Serotonin Transporter in hyperreactive platelets counteracts the pro-thrombotic effect of serotonin. 2012. J. Mol. Cell. Cardiol52:1112-21. PMID: 22366712.PMC3327821.  [Abstract]

Mercado, C., Ziu, E., Kilic, F. Communication between 5-HT and small GTPases Current Opinion in Pharmacology.  2011. 11:23-28. NIHMS271607.  [Abstract]

Mercado, C., and Kilic, F. “Molecular mechanisms of SERT in platelets: regulation of plasma serotonin levels.”   Molecular Interventions. 2010. 10:231-241. PMID: 20729489 PMC20729489.  [Abstract]

Ahmed, BA., Jeffus, B., Harney, JT., Bukhari, IS., Unal, R., Lupashin, VV.,  van der Sluijs, P., and Kilic, F. Serotonin transamidates Rab4 and facilitates binding to the C-terminus of hSERT. J  Biol Chem. 2008. 283:9388-9398. PMID: 18227069.  [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. J. Neurochem. 2007. 102:206-216. PMID:17506858.  [Abstract]

Ozaslan, D., Wang, S., Ahmed, B., Bene, A., Kocabas, AM., and Kilic, F. Glycosyl Modification Facilitates Homo- and Hetero-Oligomerization of Serotonin Transporter. A Specific Role for the Sialic Acid Residues. J. Biol. Chem. 2003. 278:43991-44000. PMID: 12944413.  [Abstract]

Kilic F, Murphy D, Rudnick G. A human serotonin trans­porter mutation cau­ses constitutive activation of trans­port activity.  Mol.  Pharm. 2003. 64:4-12. PMID: 12869649.  [Abstract]

Kilic F, Rudnick G.  Oligomerization of the serotonin transporter and its functional consequences. Proc. Natl. Acad. Sci USA 2000. 97:3106-3111. PMID: 10716733.  [Abstract]

 

Complete List of Publication

http://www.ncbi.nlm.nih.gov/sites/myncbi/14c-rKhQrsy5u/bibliography/41662594/public/?sort=date&direction=descending