Specific Clinical/Research Interest: Systems biology of cellular signaling specificity in response to drugs or viruses

Current Students: Tony Yuen, Rosalind Ang, Soon-Gang Choi, David Braun

Postdoctoral Fellows: Jeremy Seto, Boris Hartmann, Joanna Gonzalez, Robert Bowles, Liang Qiao, Laura Abizu

Research Personnel: Science Admin: Lidija Ivic, Bioinformatics: Hanna Pincus, Computer Systems: German Nudelman, Techs: Ke Jiang, Esther Rhee, Ming Chen

Associated Faculty: Fernand Hayot, Robert Pfeffer, YongChao Ge Istvan Sugar

Summary of Research Studies:
We use high throughput experiments and modeling to study signaling systems that are important for understanding cellular responses relevant to Parkinson's disease, drug abuse, viral infection and neuroendocrine reproductive function. We are interested in elucidating the molecular mechanisms underlying receptor activation and coupling to signal transduction and in placing these events in a cellular and neurobiological context. The ultimate neurobehavioral effects of an agonist evolve from the specific molecular events that accompany the interaction with its receptor and the pattern of signal transduction that is elicited. How does a specific chemical stimulus lead to the resulting downstream cellular response? In order to address this deceptively simple question we have developed new approaches to study the mechanisms underlying signal coding and signaling specificity of G-protein coupled receptors and to study responses at the single cell level in complex systems. We are investigating these issues in several experimental systems.

1) Frequency-dependent Responses of the Gondotropin-Releasing Hormone Receptor. The GnRH-R is a key mediator of the reproductive neuroendocrine system and represents a key pharmaceutical target for neoplastic and reproductive disorders. The downstream gene responses obtained in the pituitary gonadotrope depend on the frequency of receptor activation. Using gene profiling technologies, we are probing the modulation of the signaling space induced by GnRH receptor activation and developing mathematical models to explain the basis for the frequency-dependence of the pattern of gene induction.

2) Receptor Determinants of Hallucinogen Effects. Hallucinogenic drugs of abuse, such as LSD, generate their psychotropic effects through their interaction with 5-HT2 subtype receptors and the serotonin-glutamate receptor complex we have recently identified.

3) Experiment-based modeling of dendritic cell responses to viruses: We are developing experimental-data based predictive mathematical models of dendritic cell responses to pathogenic viruses.

For more information, please visit the Sealfon Laboratory website.