Lankupalle D. Jayanthi, Ph.D.
- Christian Medical College Hospital (University of Madras), India, 1992
- Medical College of Georgia, postdoctoral training
- Vanderbilt University School of Medicine, postdoctoral training
- Pharmacology and molecular neurobiology of monoamine transporters
Mood disorders like anxiety, depression and drug addiction are often linked to cardiovascular diseases, and the best way to ultimately develop effective therapeutics is through better understanding of the basic biological mechanisms involved. The catecholamine norepinephrine (NE) governs multiple functions from mood, attention, arousal and memory to cardiovascular control. Plasma membrane NE transporter (NET) is the primary regulator of NE signaling and a target for medications used in the treatment of depression and ADHD as well as for psychostimulant drugs. The overall goal of our research program is to determine the role of amine transporter phosphorylation in normal and pathophysiological settings. Both NE and neurokinin signals are implicated in cardiovascular diseases and mood disorders. In this regard, part of our research effort is focused on understanding the link between neurokinin signaling and NET modulation. Tricyclic antidepressants, and psychostimulants such as cocaine and amphetamine bind to amine transporters and differentially modulate transport function. These actions are attributed to the rewarding effects and abuse liability of these drugs. In this regard, our laboratory has been focused on understanding the differential regulation of NET by psychostimulants. Our research findings and studies of amine transporter phosphorylation represent a fundamental shift in the understanding of mechanisms underlying the actions of drugs of abuse and drug addiction.
Our laboratory has extensive experience in the use of advanced molecular and biochemical techniques, and has developed strong expertise in applying these techniques to investigate the role of transporter phosphorylation in the regulation of transport function. Ongoing research is now focused on translating our knowledge of amine transporter regulation to physiological settings. In this regard, transgenic animal models mimicking or lacking transporter phosphorylation are currently being developed. Our integrated multidisciplinary approach including electrochemical and behavioral studies will provide insights into signals regulating amine transporters and aid in the development of therapeutic strategies targeting these signals.
Annamalai B, Mannangatti P, Arapulisamy O, Shippenberg TS, Jayanthi LD and Ramamoorthy S. (2012) Tyrosine phosphorylation of the human serotonin transporter: a role in the transporter stability and function. Molecular Pharmacology. 81:73-85. PMID: 21992875; PMCID: PMC3250108
Jayanthi LD, Shippenberg TS and Ramamoorthy S. (2011) Regulation of monoamine transporters: role of transporter phosphorylation. Pharmacology and Therapeutics. 129: 220-38. PMID: 20951731; PMCID: PMC3031138
Mannangatti P, Arapulisamy O, Shippenberg TS, Ramamoorthy S and Jayanthi LD. (2011) Cocaine upregulation of the norepinephrine transporter requires threonine 30 phosphorylation by p38 mitogen-activated protein kinase. Journal of Biological Chemistry. 286:20239-50. PMID: 21498515
Annamalai B, Mannangatti P, Arapulisamy O, Ramamoorthy S and Jayanthi LD. (2010) Involvement of Threonine 258 and Serine 259 motif in amphetamine-induced norepinephrine transporter Endocytosis. Journal of Neurochemistry. 115: 23-35. PMID: 20626559; PMCID: PMC2939970
Ramamoorthy S, Samuvel DJ, Balasubraminiam A, See RE and Jayanthi LD. (2010) Altered dopamine transporter function and phosphorylation following chronic cocaine self-administration and extinction in rats. Biochemical and Biophysical Research Communications. 319:1517-21. PMID: 20035724; PMCID: PMC2812585