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Palladino Lab

The Palladino laboratory uses a combined molecular and genetic approach to identify key proteins required for neural maintenance with age and understand the role of these gene products in human disease conditions. The projects in Dr Palladino’s laboratory are directed toward three main goals: 1) discovering and characterizing novel pathways that cause neurodegenerative diseases, 2) understanding the physiological, cellular and molecular dysfunctions that cause neurodegeneration in vivo, and 3) using our animal system in pharmacological screens to identify neuroprotective compounds for the treatment of human neurodegenerative diseases.


Keri J. Fogle, PhD

The ATP61 Drosophila model of mitochondrial encephalomyopathies shares common features with human diseases, including Maternally Inherited Leigh Syndrome (MILS) and Neuropathy, Ataxia, and Retinitis Pigmentosa (NARP). Some of the hallmarks of these diseases include neurodegeneration and seizure-like activity that is often unresponsive to commonly-used anti-epileptic drugs.
 
Dr. Fogle is using whole-cell patch clamp electrophysiology of the intact fly brain to explore the molecular mechanisms which underlie the neurobiological symptoms in the ATP61 model, specifically the membrane channel complexes which may couple metabolic disruption to neuronal dysfunction and hyperexcitability, and thus represent targets for novel therapeutic interventions.    

Michael J. Palladino, PhD

The Palladino lab uses Drosophila (the fruit fly) as a genetic model system, as well as mice and human cell culture to study progressive neurological and neuromuscular disorders. We are currently focusing on elucidating the mechanism by which mutations affecting Na/K ATPase, triose phosphate isomerase (TPI), and ATP6 function result in RDP (rapid-onset dystonia parkinsonism), glycolytic enzymopthy, and mitochondrial encephalomyopathy, respectively. Our research program is directed toward four main goals 1) discovering and characterizing novel pathways that cause progressive disease, 2) understanding the physiological, cellular and molecular dysfunction that causes dysfunction in vivo, 3) understanding the molecular basis of progressive diseases, and 4) using our animal model system to identify novel therapeutic approaches.

Headshot of Keri J. Fogle, PhD
Keri J. Fogle, PhD
Research Instructor

Headshot of Michael J. Palladino, PhD
Michael J. Palladino, PhD
Professor & Vice Chair for Faculty Affairs

Keri J. Fogle, PhD

Journal Articles

Fogle KJ, KP Parson, NA Damn and TC Holmes.  Cryptochrome is a blue light sensor that modulates neuronal activity.  Science 331:1409-1413, 2011.
Sheeba V, KJ Vogle and TC  Holmes. Persistence of morning anticipation behavior and high amplitude morning startle response following functional loss of small ventral lateral neurons in Drosophila.  PLoS ONE 5:e11628, 2010.
Rozario AO, HK Turbendian, KJ Fogle, NB Olivier and GR Tibbs.  Voltage-dependent opening of HCN channels:  Facilitation by the phytoestrogen, genistein, is determined by the activation status of the cyclic nucleotide gating ring.  Biochim Biophys Acta 88:1939-1949, 2009.
Ayaz D, M Leyssen, M Koch, J Yan, M Srahna, V Sheeba, KJ Fogle, TC Holmes and BA Hassan.  Axonal injury and regeneration in the adult brain of Drosophila. J Neurosci 28:6010-6021, 2008.
Sheeba V, KJ Fogle, M Kaneko, S Rashid, YT Chou, VK Sharma and TC Holmes.  Large ventral lateral neurons modulate arousal and sleep in Drosophila.  Current Biology 18:1537-1545, 2008.
Fogle KJ, AK Lyaschenko, HK Turbendian and GR Gibbs.  HCN pacemaker channel activation is controlled by acidic lipids downstream of diacylglycerol kinase and phospholipase A2.  J Neurosci 27:2802-2814, 2007.

Michael J. Palladino, PhD

Journal Articles

Hrizo SL and MJ Palladino.  Hsp70 and Hsp90 mediate proteasomal degradation of TPIsugarkill that underlies pathogenesis.  Neurobiology of Disease 40:676-683, 2010.
Palladino MJ.  Modeling mitochondrial encephalomyopathy in Drosophila.  Neurobiology of Disease 40:40-45, 2010.
Ashmore LJ, SL Hrizo, SM Paul, W Van Voorhies, GJ Beitel and MJ Palladino.  Novel mutations affecting the NA,K ATPase alpha model complex neurological diseases and implicate the sodium pump in increased longevity.  Human Genetics 126:431-447, 2009.
Celotto AM, AC Frank, JL Seigle and MJ Palladino. Drosophila model of human inherited TPI deficiency glycolytic enzymopathy. Genetics 174:1237-1246, 2006.
Celotto AM, AC Frank, SW McGrath, TJ Fergestad, WA Van Voorhies, K Buttle, CA Mannella and MJ Palladino. Mitochondrial encephalomyopathies in drosophila. Journal of Neuroscience 26(3):810-820, 2006.
Palladino MJ, JE Bower, R Kreber and Barry Ganetzky. Neural dysfunction and neurodegeneration in Drosophila Na+/K+ ATPase alpha subunit mutants. Journal of Neuroscience 23(4):1276-1286, 2003.
Palladino MJ, TJ Hadley and B Ganetzky. Temperature-sensitive paralytic mutants are enriched for those causing neurodegeneration in Drosophila.  Genetics 161(3):1197-1208, 2002.
Palladino MJ, LP Keegan, MA O’Connell and RA Reenan. A-to-I pre-mRNA editing in Drosophila is primarily involved in adult nervous system function and integrity. Cell 102(4):437-449, 2000.