Stephen Salton, MD, PhD
- PROFESSOR | Geriatrics and Palliative Medicine
- PROFESSOR | Neuroscience
Research Topics:Adipose, Aging, Apoptosis/Cell Death, Axon Guidance, Brain, Cell Adhesion, Chromogranins and Secretogranins, Cognitive Neuroscience, Cytoskeleton, Depression, Diabetes, Growth Cone, Growth Factors and Receptors, Hormones, Memory, Neuropeptides, Neurotrophins, Obesity, Protein Phosphatases, Protein Trafficking & Sorting, Signal Transduction, Synapses
Research in the Salton lab is focused on understanding the mechanisms by which neurotrophic growth factors, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), regulate nervous system development, adult function, and the response to injury and degenerative disease.
Multi-Disciplinary Training AreaNeuroscience [NEU]
BA, University of Pennsylvania
Fellowship, Columbia Presbyterian and Mount Sinai School of Medicine
Internship and Residency, Bellevue and NYU School of Medicine
MD, New York University
PhD, New York University
NARSAD van Ameringen Investigator
NARSAD Independent Investigator
Irma T. Hirschl Career Scientist
Pew Scholar in the Biomedical Sciences
Pfizer Postdoctoral Fellow
Specific Clinical/Research Interests: Molecular Neuroscience; Neurotrophin Signaling; Neuropeptides; Neural Cell Adhesion Molecules; Obesity; Diabetes; Depression.
Current Students: PhD: Cheng Jiang (Neuroscience), MS: Masato Sadahiro, Amy Frick
Postdoctoral Fellows: Samira Fargali, Wei-Jye Lin, Jelle Welagen
Research Personnel: Valeria Cogliani
Summary of Research Studies: Our research is focused on understanding the mechanisms by which neurotrophic growth factors, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), regulate nervous system development and function. BDNF and NGF have been implicated in the pathophysiology of neurodegenerative disease, neuropsychiatric illness, CNS injury, and obesity. The contributions made by specific neurotrophin-regulated gene products to depression, memory, and energy balance, are being being examined using novel knockout, transgenic, and knockin mouse models. The lab has identified VGF, a secreted peptide precursor and granin family member, and the cell adhesion molecule (CAM) L1 or NILE, as important gene products that are induced by neurotrophin exposure during neural differentiation. Cultured neurons, neural and endocrine cell lines, and hippocampal slices are all utilized to study effects of these proteins on synaptic plasticity, neurogenesis, axonal outgrowth, and axonal pathfinding. Conservation of function of neurotrophin-regulated proteins, including VGF and L1, in simpler vertebrate models such as zebrafish, is also under investigation. We are currently determining the potential functional roles and signaling pathways of these and other neurotrophin-regulated molecules in clinically relevant diseases, including major depression, neuropathic pain, obesity, and fetal alcohol syndrome.
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Lin WJ, Jiang C, Sadahiro M, Bozdagi O, Vulchanova L, Alberini CM, Salton SR. VGF and Its C-Terminal Peptide TLQP-62 Regulate Memory Formation in Hippocampus via a BDNF-TrkB-Dependent Mechanism. J Neurosci 2015 Jul; 35(28): 10343-10356.
Sadahiro M, Erickson C, Lin WJ, Shin AC, Razzoli M, Jiang C, Fargali S, Gurney A, Kelley KA, Buettner C, Bartolomucci A, Salton SR. Role of VGF-derived carboxy-terminal peptides in energy balance and reproduction. Endocrinology 2015 May; 156(5): 1724-1738.
Fairbanks CA, Peterson CD, Speltz RH, Riedl MS, Kitto KF, Dykstra JA, Braun PD, Sadahiro M, Salton SR, Vulchanova L. The VGF-derived peptide TLQP-21 contributes to inflammatory and nerve injury-induced hypersensitivity. Pain 2014 Mar; 155(7): 1229-1237.
Fargali S, Garcia AL, Sadahiro M, Jiang C, Janssen WG, Lin WJ, Cogliani V, Elste A, Mortillo S, Cero C, Veitenheimer B, Graiani G, Pasinetti GM, Mahata SK, Osborn JW, Huntley GW, Phillips GR, Benson DL, Bartolomucci A, Salton SR. The granin VGF promotes genesis of secretory vesicles, and regulates circulating catecholamine levels and blood pressure. FASEB J 2014 Feb; 28(5): 2120-2133.
Fargali S, Scherer T, Shin AC, Sadahiro M, Buettner C, Salton SR. Germline ablation of VGF increases lipolysis in white adipose tissue. J Endocrinol 2012 Nov; 215(2).
Bartolomucci A, Possenti R, Mahata SK, Fischer-Colbrie R, Loh YP, Salton SR. The extended granin family: structure, function, and biomedical implications. Endocr Rev 2011 Dec; 32(6).
Carcea I, Ma'ayan A, Mesias R, Sepulveda B, Salton SR, Benson DL. Flotillin-mediated endocytic events dictate cell type-specific responses to semaphorin 3A. J Neurosci 2010 Nov; 30(45).
Watson E, Fargali S, Okamoto H, Sadahiro M, Gordon RE, Chakraborty T, Sleeman MW, Salton SR. Analysis of knockout mice suggests a role for VGF in the control of fat storage and energy expenditure. BMC Physiol 2009; 9.
Moss A, Theodorou A, Low L, Ingram R, Kock S, Baccei M, Hathway GJ, Costigan M, Salton SR, Fitgerald M. Origins, actions and dynamic expression patterns of the neuropeptide VGF in rat peripheral and central sensory neurons following peripheral nerve injury. Mol Pain 2008 Dec; 4(1): 62.
Bozdagi O, Rich E, Tronel S, Sadahiro M, Patterson K, Shapiro ML, Alberini C, Huntley GW, Salton SR. The neurotrophin-inducible gene Vgf regulates hippocampal function and behavior through a BDNF-dependent mechanism. J Neurosci 2008; 28: 9857-9869.
Mintz CD, Carcea I, Burke ME, McNickle DG, Ge YC, Dickson TC, Salton SR, Benson DL. ERM proteins regulate response and adaptation to Sema3A. J Comp Neurol 2008; 510: 351-366.
Hunsberger JG, Newton SS, Bennett AH, Duman CH, Russell DS, Salton SR, Duman RS. Novel antidepressant actions of the exercise-regulated gene VGF. Nat Med 2007 Dec; 13(12): 1476-1482.
Watson E, Hahm S, Mizuno TM, Windsor J, Montgomery C, Scherer PE, Mobbs CV, Salton S. VGF ablation blocks the development of hyperinsulinemia and hyperglycemia in several mouse models of obesity. Endocrinology 2005 Dec; 146(12): 5151-63.
Garcia AL, Han SK, Janssen WG, Khaing ZZ, Ito T, Glucksman MJ, Benson DL, Salton SR. A prohormone convertase cleavage site within a predicted alpha-helix mediates sorting of the neuronal and endocrine polypeptide VGF into the regulated secretory pathway. J Biol Chem 2005 Dec 16; 280(50): 41595-608.
Hahm S, Fekete C, Mizuno TM, Windsor J, Yan H, Boozer CN, Lee C, Elmquist JK, Lechan RM, Mobbs CV, Salton SV. VGF is required for obesity induced by diet, gold thioglucose treatment and agouti, and is differentially regulated in POMC- and NPY-containing arcuate neurons in response to fasting. J Neurosci 2002; 22: 6929-6938.
Hahm S, Mizuno TM, Wu TJ, Wisor JP, Priest CA, Kozak CA, Boozer CN, Peng B, Mc Evoy RC, Good P, Kelley KA, Takahashi JS, Pintar JE, Roberts JL, Mobbs CV, Salton SR. Targeted deletion of the Vgf gene indicates that the encoded secretory peptide precursor plays a novel role in the regulation of energy balance. Neuron 1999 Jul; 23(3): 537-48.