Human Immune Cell Signaling

1. Experimental Based Dendritic Cell modeling
   We have established a multidisciplinary Immune Modeling Center to develop mathematical models to elucidate the viral mechanisms of induction and subversion of type 1 interferon responses and maturation of dendritic cells by Category A-C viral pathogens. The objectives of the Center are:
   
   1. Develop robust cellular models that describe and predict the response of human myeloid dendritic cells to specific class A-C viral pathogens and their components.
   2. Experimentally constrain, test and refine the mathematical models.
   3. Develop a bioinformatics component for data management, model development, communication among investigators, and dissemination of models and data.
   4. Develop an education program for trainees working with the Center and visiting scientists. The closely coordinated research and educational efforts at four entities-Mount Sinai School of Medicine, Princeton University, Ohio State University, and BioAnalytics Group LLC-provide a unique opportunity to use computational approaches to advance the understanding of the molecular mechanisms of action of viral antagonism and to provide the foundation for improved vaccines and immunotherapeutics against Category A-C Priority Pathogens.
2. Technology Development for Studying Human Immune Cell Responses:
   

   As part of the Center for Viral Immunity and Antagonism at Mount Sinai (www.civia.org) we are developing genomic and proteomic approaches to characterize the human dendritic cell and T cell responses.

Gonadotrope Signaling

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 genomics, proteomics, single cell assays, and computational/mathematical approaches, we are probing the modulation of the signaling space induced by gonadotrope stimulation and developing models to explain the basis for the specificity of biosynthetic responses.

Pyramidal Neuron Signaling: Receptor Determinants of Hallucinogen Effects

Hallucinogenic drugs of abuse, such as LSD, generate their psychotropic effects through their interaction with 5-HT2 subtype receptors. The hallmark of this interaction, which is specific to their unique neuropsychological actions is unknown. Studies into the molecular mechanism of receptor activation by serotonin agonists, using mutagenesis, pharmacological evaluation, gene profiling techniques and knock-in in vivo model systems are being undertaken in order to elucidate the molecular and systemic actions of hallucinogens.

Brain Genome Anatomy

We are developing and using multiplex histological gene and protein expression assays to develop a multidimensional single cell map of selected regions of the mouse brain.