Back to Main

Faculty Detail    
Name LUCAS D POZZO-MILLER
  
Campus Address SHEL 907
Phone  (205) 934-0739
E-mail  lucaspm@uab.edu
Other websites Google Scholar
Twitter
UAB Neurobiology page
UAB Faculty Page
Scholars@UAB
     

Education
Undergraduate  Universidad Nacional de Cordoba, Argentina    1986  BS, MS 
Graduate  Universidad Nacional de Cordoba, Argentina    1989  PhD 


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Neurobiology  Neurobiology Professor

Graduate Biomedical Sciences Affiliations
Cell, Molecular, & Developmental Biology 
Cellular and Molecular Biology Program 
Comprehensive Neuroscience Center 
Genetics, Genomics and Bioinformatics 
Hughes Med-Grad Fellowship Program 
Integrative Biomedical Sciences 
Medical Scientist Training Program 
Neuroscience 
Neuroscience Graduate Program 
Neurosciences 

Biographical Sketch 
Lucas Pozzo-Miller completed his undergraduate studies in Biology (MS, 1986) and earned his graduate degree in Neurobiology from the Universidad Nacional de Córdoba, Argentina (PhD, 1989). He trained as postdoctoral fellow at Case Western Reserve University, Cleveland OH, with Dr. Dennis Landis (1990-1992), and at the Roche Institute of Molecular Biology, Nutley NJ, with Dr. John Connor (1992-1995). He performed research at the Marine Biological Laboratory, Woods Hole MA, with Dr. Rodolfo Llinás (1994 Grass Foundation Fellow, and 1995 Lakian Foundation Fellow). He held a Senior Staff Fellow position at the National Institutes of Health, Bethesda MD, in the laboratory of Dr. Tom Reese (1995-1998), and joined the faculty of the Department of Neurobiology at the University of Alabama at Birmingham in 1998. He is Professor of Neurobiology, Co-Director of the Comprehensive Neuroscience Center, and Co-Director of the Neuroscience graduate program.

Society Memberships
Organization Name Position Held Org Link
Society for Neuroscience  Member  http://web.sfn.org/ 
The American Physiological Society  Member  http://www.the-aps.org/index.htm 
 



Research/Clinical Interest
Title
Neurotrophins in Synapse Development and Plasticity, Intellectual Disabilities, and Syndromic Autisms
Description
Our long-term interest is to characterize the functional role of different cellular compartments in neurons, such as dendritic spines and presynaptic terminals, and how they participate in the development, function, and plasticity of synapses as they relate to learning & memory and social behaviors. Neurotrophins, like brain-derived neurotrophic factor (BDNF), are secretory proteins that regulate the survival and differentiation of neurons during early brain development, and also synapse function and plasticity throughout the lifetime. We investigate the “BDNF hypothesis” of Rett syndrome, a neurodevelopmental disorder associated with autistic features and intellectual disabilities that is caused by mutations in MECP2, a transcriptional regulator of many genes, including Bdnf. We use transgenic mice that express mutant Mecp2 as experimental models to characterize the molecular and cellular pathophysiology of Rett syndrome, and to test novel therapeutic approaches. In our studies, we apply several experimental approaches, including intracellular whole-cell recordings, voltage-sensitive dye and intracellular Ca2+ imaging, confocal microscopy, time-lapse imaging, multiphoton excitation microscopy, electron microscopy, and machine-learning behavioral assays.

Selected Publications 
Publication PUBMEDID
Larimore JL, Chapleau CA, Kudo S, Theibert A, Percy AK, Pozzo-Miller L. Bdnf overexpression in hippocampal neurons prevents dendritic atrophy caused by Rett-associated MECP2 mutations. Neurobiol Dis. 2009 May;34(2):199-211.  19217433 
Chapleau CA, Calfa GD, Lane MC, Albertson AJ, Larimore JL, Kudo S, Armstrong DL, Percy AK, Pozzo-Miller L. Dendritic spine pathologies in hippocampal pyramidal neurons from Rett syndrome brain and after expression of Rett-associated MECP2 mutations. Neurobiol Dis. 2009 Aug;35(2):219-33.  19442733 
Li Y, Calfa G, Inoue T, Amaral MD, Pozzo-Miller L. Activity-dependent release of endogenous BDNF from mossy fibers evokes a TRPC3 current and Ca2+ elevations in CA3 pyramidal neurons. J Neurophysiol. 2010 May;103(5):2846-56.  20220070 
Calfa G, Percy AK, Pozzo-Miller L. Experimental models of Rett syndrome based on Mecp2 dysfunction. Exp Biol Med (Maywood). 2011 Jan;236(1):3-19.  21239731 
Calfa G, Hablitz JJ, Pozzo-Miller L. Network hyperexcitability in hippocampal slices from Mecp2 mutant mice revealed by voltage-sensitive dye imaging. J Neurophysiol. 2011 Apr;105(4):1768-84.  21307327 
Calfa G, Chapleau CA, Campbell S, Inoue T, Morse SJ, Lubin FD, Pozzo-Miller L. HDAC activity is required for BDNF to increase quantal neurotransmitter release and dendritic spine density in CA1 pyramidal neurons. Hippocampus. 2012 Jul;22(7):1493-500.  22161912 
Chapleau CA, Pozzo-Miller L. Divergent roles of p75NTR and Trk receptors in BDNF's effects on dendritic spine density and morphology. Neural Plast. 2012;2012:578057.  22548193 
Hartmann D, Drummond J, Handberg E, Ewell S, Pozzo-Miller L. Multiple approaches to investigate the transport and activity-dependent release of BDNF and their application in neurogenetic disorders. Neural Plast. 2012;2012:203734.   22720171 
Amaral MD, Pozzo-Miller L. Intracellular Ca2+ stores and Ca2+ influx are both required for BDNF to rapidly increase quantal vesicular transmitter release. Neural Plast. 2012;2012:203536.  22811938 
Leuner K, Li W, Amaral MD, Rudolph S, Calfa G, Schuwald AM, Harteneck C, Inoue T, Pozzo-Miller L. Hyperforin modulates dendritic spine morphology in hippocampal pyramidal neurons by activating Ca(2+) -permeable TRPC6 channels. Hippocampus. 2013 Jan;23(1):40-52.  22815087 
Chapleau CA, Boggio EM, Calfa G, Percy AK, Giustetto M, Pozzo-Miller L. Hippocampal CA1 pyramidal neurons of Mecp2 mutant mice show a dendritic spine phenotype only in the presymptomatic stage. Neural Plast. 2012;2012:976164.   22919518 
Li W, Calfa G, Larimore J, Pozzo-Miller L. Activity-dependent BDNF release and TRPC signaling is impaired in hippocampal neurons of Mecp2 mutant mice. Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):17087-92.   23027959 
Li W, Pozzo-Miller L. BDNF deregulation in Rett syndrome. Neuropharmacology. 2014 Jan;76 Pt C:737-46.  23597512 
Li W, Pozzo-Miller L. Beyond Widespread Mecp2 Deletions to Model Rett Syndrome: Conditional Spatio-Temporal Knockout, Single-Point Mutations and Transgenic Rescue Mice. Autism Open Access. 2012;2012(Suppl 1):5  23946910 
Xu X, Kozikowski AP, Pozzo-Miller L. A selective histone deacetylase-6 inhibitor improves BDNF trafficking in hippocampal neurons from Mecp2 knockout mice: implications for Rett syndrome. Front Cell Neurosci. 2014 Mar 7;8:68.  24639629 
Calfa G, Li W, Rutherford JM, Pozzo-Miller L. Excitation/inhibition imbalance and impaired synaptic inhibition in hippocampal area CA3 of Mecp2 knockout mice. Hippocampus. 2015 Feb;25(2):159-68.  25209930 
Xu X, Miller EC, Pozzo-Miller L. Dendritic spine dysgenesis in Rett syndrome. Front Neuroanat. 2014 Sep 10;8:97.  25309341 
Phillips M, Pozzo-Miller L. Dendritic spine dysgenesis in autism related disorders. Neurosci Lett. 2015 Aug 5;601:30-40.  25767435 
Pozzo-Miller L, Pati S, Percy AK. Rett Syndrome: Reaching for Clinical Trials. Neurotherapeutics. 2015 Jul;12(3):631-40.  25861995 
Li W, Xu X, Pozzo-Miller L. Excitatory synapses are stronger in the hippocampus of Rett syndrome mice due to altered synaptic trafficking of AMPA-type glutamate receptors. Proc Natl Acad Sci U S A. 2016 Feb 29. pii: 201517244. [Epub ahead of print]  26929363 
Xu X, Pozzo-Miller L. EEA1 restores homeostatic synaptic plasticity in hippocampal neurons from Rett syndrome mice. J Physiol. 2017 Jun 16. doi: 10.1113/JP274450. [Epub ahead of print]  28621434 
Li W, Bellot-Saez A, Phillips ML, Yang T, Longo FM, Pozzo-Miller L. A small-molecule TrkB ligand restores hippocampal synaptic plasticity and object location memory in Rett syndrome mice. Dis Model Mech. 2017 Jul 1;10(7):837-845  28679669 
Xu X, Garcia J, Ewalt R, Nason S, Pozzo-Miller L. The BDNF val-66-met Polymorphism Affects Neuronal Morphology and Synaptic Transmission in Cultured Hippocampal Neurons from Rett Syndrome Mice. Front Cell Neurosci. 2017 Jul 13;11:203  28751857 
 

Keywords
BDNF, Ca2+, Synapse, Rett Syndrome, Hippocampus, Dendritic Spines, MeCP2, Autism, Intellectual Disability