Gender	Male
E-mail	stephen.salton@mssm.edu
Education and Training	B.A., University of Pennsylvania
	MD Ph.D., New York University
	Residency, Bellevue and NYU
	Postdoctoral Training, Columbia University and Mount Sinai
Awards	2006 - 2010 NARSAD Independent Investigator
	1994 - 1999 Irma T. Hirschl Career Scientist
	1991 - 1995 Pew Scholar in the Biomedical Sciences
	1989 - 1991 Pfizer Scholar
	1986 - 1988 Pfizer Postdoctoral Fellow

Visit Dr. Stephen Salton's Lab for more information.

Education and Training	B.A., University of Pennsylvania
	MD Ph.D., New York University
	Residency, Bellevue and NYU
	Postdoctoral Training, Columbia University and Mount Sinai

Research

Specific Clinical/Research Interest:
Molecular neurobiology; neurotrophin signaling; novel neuropeptides and obesity; neural cell adhesion molecules
Current Students: PhD: Angelo Garcia (MDT)
Postdoctoral Fellows: Samira Fargali
Research Personnel: Masato Sadahiro
Summary of Research Studies:
We are interested in understanding how neural genes are regulated by neurotrophic growth factors in the developing and adult mammalian central and peripheral nervous systems. We have identified several gene products that are relatively selectively regulated by neurotrophic growth factors in PC12 cells, a cell line that differentiates into neurons in response to nerve growth factor (NGF). Our laboratory is currently studying two of these gene products, the adhesion molecule L1 and the secreted polypeptide VGF. VGF expression is rapidly and robustly induced in neurons and PC12 cells, and is upregulated in the brain following seizure and cortical injury; this gene encodes a polypeptide that is released from dense core vesicles and is cleaved into bioactive peptides. Based on our studies of VGF knockout mice that are lean and hypermetabolic, and resistant to obesity and diabetes, this molecule appears to play a critical role in regulating energy expenditure. In addition, st! udies further suggest that VGF peptides injected into the brain have antidepressant characteristics, regulating hippocampal neurogenesis and synaptic plasticity, consistent with abnormalities noted in memory tasks and depressed behavior in VGF mutant mice. We are currently examining VGF function(s) in the developing and adult nervous system, identifying its mechanism(s) of action, screening for cell surface receptors, investigating association of the human VGF locus with obesity and depression, and trying to more broadly define the role that neurotrophins play in the adult to regulate feeding, energy expenditure, memory, and depression. L1, inducible by NGF-treatment in PC12 cells, is a cell surface protein of the immunoglobuline (Ig) superfamily that is expressed primarily in the nervous system where it regulates axonal outgrowth, pathfinding, and fasciculation as well as neuronal migration. Hereditary, X-linked mutations in L1 result in hydrocephalus and mental retardation, and similarities between fetal alcohol syndrome (FAS) and these neurological diseases have suggested that L1 may be a target for ethanol. We have been studying the function of L1 by trying to better understand how L1 is selectively targeted to axons and what intracellular signaling pathways are stimulated by L1-mediated adhesion. We have recently identified novel interactions between L1 and the Ezrin-Radixin-Moesin (ERM) family of actin linker proteins that regulate L1-dependant axonal branching and pathfinding. Additional L1 interacting proteins are currently being characterized and their role(s) in transducing L1 adhesion signals. In neurons, which are highly polarized cells, various proteins have to be very selectively targeted to different regions for functional expression and/or regulated release. For example, adhesion molecules such as NILE/L1 and telencephalin are selectively targeted to axons and dendrites, respectively, while the secreted polypeptide VGF is sorted into large dense core vesicles for regulated release. We are currently trying to identify the mechanisms, polypeptide signals, and sorting receptors that are responsible for targeting proteins into different intracellular compartments of the polarized neuron. In addition, we have recently initiated studies that examine the vulnerability of hippocampal neurons to hypoglycemia, as a model for understanding the mechanisms by which transient hypoglycemia during pregnancy can lead to cognitive damage in the adult.

Visit Dr. Stephen Salton's Lab for more information.

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.

Sakurai T, Gil OG, Whittard JD, Gazdoiu M, Joseph T, Wu J, Waksman A, Benson DL, Salton SR, Felsenfeld DP. Interactions between L1 cell adhesion molecule and ezrin support traction-force generation and can be regulated by tyrosine phosphorylation. J. Neurosci. Res 2008; 86: 2602-2614.

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.

Dickson TC, Mintz CD, Benson DL, Salton SR. Functional binding interaction identified between the axonal CAM L1 and members of the ERM family. J Cell Biol 2002 Jun 24; 157(7): 1105-12.

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.