Stuart C Sealfon, MD
- PROFESSOR | Neurology
- PROFESSOR | Neuroscience
- PROFESSOR | Pharmacological Sciences
Research Topics:Addiction, Apoptosis/Cell Death, Basal Ganglia, Bioinformatics, Brain, Cellular Immunity, Cerebral Cortex, Mathematical and Computational Biology, Multiple Sclerosis, Neuro-degeneration/protection, Receptors, Reproductive Biology, Signal Transduction, Theoretical Biology, Vaccine Development, Viruses and Virology
Stuart C. Sealfon, M.D. is the Glickenhaus Professor and Chairman Emeritus of the Department of Neurology, Director of the Center for Genomics, Proteomics and Bioinformatics, Director of the Center for Translational Systems Biology, Professor of Neurobiology, and Professor of Pharmacology and Systems Therapeutics at Mount Sinai Hospital and School of Medicine.
Dr. Sealfon has made important contributions to research on receptor structure, cell signaling, mechanisms of drug specificity and systems biology. His work integrates experimental and theoretical approaches, encompasses several areas of brain research, and is supported by the National Institute of Drug Abuse, the National Institute of Diabetes, Digestive and Kidney Diseases and the National Institute of Allergy and Infectious Disease. He directs the multi-institutional Program for Research on Immune Modeling and Experimentation (PRIME), an NIH-funded Modeling Immunity for Biodefense Center.
Several of his research studies have been recognized by the Faculty of 1000 Biology and the Faculty of 1000 Medicine. His laboratory has pioneered numerous research approaches including techniques for microarray design and analysis, transcription-based assays for profiling drug responses, single cell assays of cellular signaling and quantum dot-based assays of gene and protein expression in single brain cells. Significant research accomplishments include: identifying the primary structure of the gonadotropin releasing hormone receptor, finding new signaling pathways activated by drugs for Parkinson's disease, elucidating the mechanism of action of hallucinogens and finding a new brain receptor complex implicated in schizophrenia and as a novel target for antipsychotic drugs.
A graduate of Princeton University and Columbia University College of Physicians and Surgeons, Dr. Sealfon in a member of Phi Beta Kappa and Alpha Omega Alpha. He received his residency training at Massachusetts General Hospital, Boston. He has been associated with the Mount Sinai School of Medicine for more than two decades, initially as a postdoctoral trainee in Neuroscience and subsequently as a member of the faculty. He holds board certification in Neurology.
Dr. Sealfon has contributed to more than 100 patents and original research articles, primarily related to receptors, cell signaling and brain disease. He is a noted mentor and educator. Dr. Sealfon has served on the editorial boards of numerous peer-reviewed journals and scientific advisory boards, and has lectured at universities and conferences throughout the world.
Neurology, American Board of Psychiatry and Neurology
Multi-Disciplinary Training AreasImmunology [IMM], Neuroscience [NEU], Pharmacology and Therapeutics Discovery [PTD]
MD, Columbia-Presbyterian Medical Center
MD, Columbia University College of Physicians & Surgeons
Internship, Internal Medicine, Massachusetts General Hospital
Residency, Neurology, Massachusetts General Hospital
''Identification of a serotonin/glutamate receptor complex implicated in psychosis'' rated ''Exceptional'' by Faculty of 1000, Biology, and ''Must Read'' by Faculty of 1000, Medicine
''BioPP: a tool for web-publication of biological networks'' rated ''Highly Accessed,'' BMC Bioinformatics
''Cortical 5-HT2A receptor signaling modulates anxiety-like behaviors in mice'' rated ''Recommended'' by Faculty of 1000, Biology
''Early single cell bifurcation of pro-and anti-apoptotic states during oxidative stress'' rated ''Must Read'' by Faculty of 1000, Biology
Alpha Omega Alpha
Sciarra Prize in Neurology
Sandoz Award for Neuroscience Research
Phi Beta Kappa
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.
Viswanathan G, Jayaprakash C, Sealfon SC, Hayot F. Shared kinase fluctuations between two enzymatic reactions. Phys Biol 2008; 5: 46002-46011.
Borderia AV, Hartmann BM, Fernandez-Sesma A, Moran TM, Sealfon SC. Antiviral-activated dendritic cells: a paracrine-induced response state. J Immunol 2008; 181: 6872-6878.
Gonzalez-Maeso J, Ang RL, Yuen T, Chan P, Weisstaub NV, Lopez-Gimenez JF, Zhou M, Okawa Y, Callado LF, Milligan G, Gingrich JA, Filizola M, Meana JJ, Sealfon SC. Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature 2008 Mar; 452(7183): 93-97.
Ruf F, Hayot F, Park MJ, Ge Y, Lin G, Roysam B, Sealfon SC. Noise propagation and scaling in regulation of gonadotrope biosynthesis. Biophys J 2007 Dec 15; 93(12): 4474-4480.
Viswanathan GA, Nudelman G, Patil S, Sealfon SC. BioPP: a tool for web-publication of biological networks. BMC Bioinformatics 2007 May 22; 8: 168.
Gonzalez-Maeso J, Weisstaub NV, Zhou M, Chan P, Ivic L, Ang R, Lira A, Ge Y, Zhou Q, Sealfon SC, Gingrich JA. Hallucinogens recruit specific cortical 5-HT (2A) receptor-mediated signaling pathways to affect behavior. Neuron 2007 Feb 1; 53(3): 439-452.
Ruf F, Park MJ, Hayot F, Lin G, Roysam B, Ge Y, Sealfon SC. Mixed analog/digital gonadotrope biosynthetic response to gonadotropin-releasing hormone. J Biol Chem 2006 Oct 13; 281(41): 30967-30978.
Weisstaub NV, Zhou M, Lira A, Lambe E, Gonzalez-Maeso J, Hornung JP, Sibille E, Underwood M, Itohara S, Dauer WT, Ansorge MS, Morelli E, Mann JJ, Toth M, Aghajanian G, Sealfon SC, Hen R, Gingrich JA. Cortical 5-HT2A receptor signaling modulates anxiety-like behaviors in mice. Science 2006; 313(5786): 536-540.
GE Y, Sealfon S, Speed T. Multiple testing and its applications to microarrays. Stat Methods Med Res 2009; 18(6): 543-563.
Hu J, Iyer-Biswas S, Sealfon SC, Wetmur J, Jayaprakash C, Hayot F. Power-laws in interferon-B mRNA distribution in virus-infected dendritic cells. Biophysical journal 2009 Oct; 97(7).
Sugár IP, Sealfon SC. Model of autocrine/paracrine signaling in epithelial layer: geometrical regulation of intercellular communication. The journal of physical chemistry. B 2009 Aug; 113(31).
Yuen T, Ruf F, Chu T, Sealfon SC. Microtranscriptome regulation by gonadotropin-releasing hormone. Molecular and cellular endocrinology 2009 Apr; 302(1).
Shimoni Y, Fink MY, Choi SG, Sealfon SC. Plato's cave algorithm: inferring functional signaling networks from early gene expression shadows. PLoS computational biology 2010 Jun; 6(6).
Nudelman G, Ge Y, Hu J, Kumar M, Seto J, Duke JL, Kleinstein SH, Hayot F, Sealfon SC, Wetmur JG. Coregulation mapping based on individual phenotypic variation in response to virus infection. Immunome research 2010; 6.
Zaslavsky E, Hershberg U, Seto J, Pham AM, Marquez S, Duke JL, Wetmur JG, Tenoever BR, Sealfon SC, Kleinstein SH. Antiviral response dictated by choreographed cascade of transcription factors. Journal of immunology (Baltimore, Md. : 1950) 2010 Mar; 184(6).
Qiao L, Phipps-Yonas H, Hartmann B, Moran TM, Sealfon SC, Hayot F. Immune response modeling of interferon beta-pretreated influenza virus-infected human dendritic cells. Biophysical journal 2010 Feb; 98(4).
Sugár IP, Sealfon SC. Misty Mountain clustering: application to fast unsupervised flow cytometry gating. BMC bioinformatics 2010; 11.
Sugár IP, Sealfon SC. Misty Mountain clustering: application to fast unsupervised flow cytometry gating. BMC bioinformatics 2010; 11.
Bowles R, Patil S, Pincas H, Sealfon SC. Validation of efficient high-throughput plasmid and siRNA transfection of human monocyte-derived dendritic cells without cell maturation. Journal of immunological methods 2010 Dec; 363(1).
Seto J, Qiao L, Guenzel CA, Xiao S, Shaw ML, Hayot F, Sealfon SC. Novel Nipah virus immune-antagonism strategy revealed by experimental and computational study. Journal of virology 2010 Nov; 84(21).
Fink MY, Pincas H, Choi SG, Nudelman G, Sealfon SC. Research resource: Gonadotropin-releasing hormone receptor-mediated signaling network in LbetaT2 cells: a pathway-based web-accessible knowledgebase. Molecular endocrinology (Baltimore, Md.) 2010 Sep; 24(9).
Choi SG, Ruf-Zamojski F, Pincas H, Roysam B, Sealfon SC. Characterization of a MAPK scaffolding protein logic gate in gonadotropes. Molecular endocrinology (Baltimore, Md.) 2011 Jun; 25(6).
Moreno JL, Holloway T, Albizu L, Sealfon SC, González-Maeso J. Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists. Neuroscience letters 2011 Apr; 493(3).
Albizu L, Holloway T, González-Maeso J, Sealfon SC. Functional crosstalk and heteromerization of serotonin 5-HT2A and dopamine D2 receptors. Neuropharmacology 2011 Sep; 61(4).
Shimoni Y, Nudelman G, Hayot F, Sealfon SC. Multi-scale stochastic simulation of diffusion-coupled agents and its application to cell culture simulation. PloS one 2011; 6(12).
Hu J, Nudelman G, Shimoni Y, Kumar M, Ding Y, López C, Hayot F, Wetmur JG, Sealfon SC. Role of cell-to-cell variability in activating a positive feedback antiviral response in human dendritic cells. PloS one 2011; 6(2).
Sugár IP, González-Lergier J, Sealfon SC. Authors response to correspondence about an improved compensation method. Cytometry. Part A : the journal of the International Society for Analytical Cytology 2011 Dec; 79(12).
Fribourg M, Moreno JL, Holloway T, Provasi D, Baki L, Mahajan R, Park G, Adney SK, Hatcher C, Eltit JM, Ruta JD, Albizu L, Li Z, Umali A, Shim J, Fabiato A, MacKerell AD, Brezina V, Sealfon SC, Filizola M, González-Maeso J, Logothetis DE. Decoding the signaling of a GPCR heteromeric complex reveals a unifying mechanism of action of antipsychotic drugs. Cell 2011 Nov; 147(5).
Yuen T, Choi SG, Pincas H, Waring DW, Sealfon SC, Turgeon JL. Optimized amplification and single-cell analysis identify GnRH-mediated activation of Rap1b in primary rat gonadotropes. Molecular and cellular endocrinology 2012 Mar; 350(1).
Ge Y, Sealfon SC. flowPeaks: a fast unsupervised clustering for flow cytometry data via K-means and density peak finding. Bioinformatics (Oxford, England) 2012 Aug; 28(15).
Choi SG, Jia J, Pfeffer RL, Sealfon SC. G proteins and autocrine signaling differentially regulate gonadotropin subunit expression in pituitary gonadotrope. The Journal of biological chemistry 2012 Jun; 287(25).
Moreno JL, Muguruza C, Umali A, Mortillo S, Holloway T, Pilar-Cuéllar F, Mocci G, Seto J, Callado LF, Neve RL, Milligan G, Sealfon SC, López-Giménez JF, Meana JJ, Benson DL, González-Maeso J. Identification of three residues essential for 5-hydroxytryptamine 2A-metabotropic glutamate 2 (5-HT2A·mGlu2) receptor heteromerization and its psychoactive behavioral function. The Journal of biological chemistry 2012 Dec; 287(53).
Nair VD, Ge Y, Balasubramaniyan N, Kim J, Okawa Y, Chikina M, Troyanskaya O, Sealfon SC. Involvement of histone demethylase LSD1 in short-time-scale gene expression changes during cell cycle progression in embryonic stem cells. Molecular and cellular biology 2012 Dec; 32(23).
Moreno JL, Holloway T, Umali A, Rayannavar V, Sealfon SC, González-Maeso J. Persistent effects of chronic clozapine on the cellular and behavioral responses to LSD in mice. Psychopharmacology 2013 Jan; 225(1).
Braun DA, Fribourg M, Sealfon SC. Cytokine response is determined by duration of receptor and signal transducers and activators of transcription 3 (STAT3) activation. The Journal of biological chemistry 2013 Feb; 288(5).
Zaslavsky E, Nudelman G, Marquez S, Hershberg U, Hartmann BM, Thakar J, Sealfon SC, Kleinstein SH. Reconstruction of regulatory networks through temporal enrichment profiling and its application to H1N1 influenza viral infection. BMC bioinformatics 2013; 14 Suppl 6.
Moreno JL, Holloway T, Rayannavar V, Sealfon SC, González-Maeso J. Chronic treatment with LY341495 decreases 5-HT(2A) receptor binding and hallucinogenic effects of LSD in mice. Neuroscience letters 2013 Mar; 536.
Wang Q, Chikina M, Zaslavsky E, Pincas H, Sealfon SC. β-catenin regulates GnRH-induced FSHβ gene expression. Molecular endocrinology (Baltimore, Md.) 2013 Feb; 27(2).
Hartmann BM, Li W, Jia J, Patil S, Marjanovic N, Martínez-Romero C, Albrecht RA, Hayot F, García-Sastre A, Wetmur JG, Moran TM, Sealfon SC. Mouse dendritic cell (DC) influenza virus infectivity is much lower than that for human DCs and is hemagglutinin subtype dependent. Journal of virology 2013 Feb; 87(3).
Tabbaa OP, Nudelman G, Sealfon SC, Hayot F, Jayaprakash C. Noise propagation through extracellular signaling leads to fluctuations in gene expression. BMC systems biology 2013; 7.