Samuel Todd Lamitina, Ph.D.

faculty photo
Department: Physiology

Contact information
A700 Richards Research Building
Philadelphia, PA 19104
Office: 215-898-3223
Education:
BS (Biology)
Emory University, 1995.
PhD (Cell and Developmental Biology)
Emory University, 2002.
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Description of Research Expertise

Research Interests
Molecular mechanisms of ion transport pathways in C. elegans

Key words: Synaptic transmission, neuromuscular junction, muscular dystrophy, osmoregulation, salt and water balance, environmental stress, C. elegans, RNAi screening

Description of Research
Regulation of ion and water movement is a crucial feature of cell physiology and is utilized to drive important and diverse physiological events, such as cell growth, cell death, fertilization, and synaptic transmission, to name a few. In many cases, the molecular/cellular/organismal mechanisms that regulate ion transport activity are poorly understood. We are using the model organism C. elegans to explore theses mechanisms, with the hope of shedding new light on human physiology and disease. Several project are ongoing in the lab:

1)Molecular mechanisms of osmoregulation - Regulation of cell volume underlies almost all aspects of cell physiology, yet we have virtually no understanding of how cells regulate or maintain their size. Using genetic approaches in C. elegans, we have uncovered a novel pathway required for animal osmoregulation. Recently, we found that extracellular mucins play a critical role in this pathway, suggesting that monitoring of cell volume may involve mechanotransduction-like mechanisms.

2) A C. elegans model for Cystic Fibrosis - Mutations in the chloride ion channel CFTR cause Cystic Fibrosis. 90% of human CF patients carry the deltaF508 mutation, which forms a functional ion channel but fails to reach the plasma membrane due to misfolding and degradation of the mutant channel in the endoplasmic reticulum. A better understanding of the mechanisms that lead to channel degradation could lead to new therapeutic options for this currently incurable disease. Using a novel transgenic approach in C. elegans, we have created the first genetically accessible animal model that recapitulates the key phenotypic features of the deltaF508 mutation. Using this model, we are performing forward genetic screens for mutants that can stabilize deltaF508 CFTR. Human homologs of these genes may represent CF risk factors in humans, as well as potential therapeutic targets for CF therapy.

3) Functional genomic analysis of synaptic transmission - Muscle contraction is regulated by activation of post-synaptic ion channels called acetylcholine receptors. While several regulators of these channels are known, a comprehensive understanding of their regulation is lacking. By combining a simple pharmacological assay with genome-wide in vivo RNAi screening methods, we have explored the role of all ~20,000 C. elegans protein coding genes in cholinergic synaptic transmission. Our screen identified known regulators of cholinergic signaling, as well as many genes not previously known to regulate these receptors. One novel gene identified through these efforts is the C. elegans Dysferlin homolog fer-1. In humans, Dysferlin mutations cause a rare and incurable form of muscular dystrophy (LGMD2B) that was not previously thought to involve defects in synaptic transmission. In collaboration with the Khurana lab (Dept. of Physiology), we are exploring whether cholinergic defects are present in a mouse model of Dysferlin muscular dystrophy and whether such defects may contribute to disease pathogenesis in humans.

4) Genetic and Biophysical analysis of a novel calcium ion channel linked to Alzheimer's disease. Dysregulation of cellular calcium homeostasis is emerging as a key pathological feature of several neurodegenerative disease states. Recent work linked mutations in the human gene Calhm1 to late-onset Alzheimer's disease. Calhm1 appears to encode a member of a novel ion channel family. While Calhm1 is linked to AD, the physiological function(s) of Calhm1 is unknown. While humans express six Calhm homologs, C. elegans contains a single Calhm homolog, clhm-1. Using this simpler system, we are using electrophysiological, genetic, and behavioral assays to better understand the biophysical properties and in vivo physiological functions of clhm-1.

Depending on the interests of the student, several rotation projects are possible. Please contact Dr. Lamitina directly with inquiries.

Lab personnel:
Tim Chaya - Research Technician
Liping He, Ph.D. - Research Technician
Lorenza Moronetti - Research Technician
Predrag Krajacic, M.D. - Postdoctoral fellow
Jessica Tanis, Ph.D. - Postdoctoral fellow
Jennifer Skirkanich, Ph.D. - Postdoctoral fellow
Elizabeth Morton - CAMB graduate student
Travis Gingerich - Undergraduate researcher
Shalyn Stevens - Undergraduate researcher

Selected Publications

Anne-Katrin Rohlfing, Yana Miteva, Lorenza Moronetti, Liping He, & Todd Lamitina: The C. elegans Mucin-Like Protein OSM-8 Negatively Regulates Osmosensitive Physiology Via the Transmembrane Protein PTR-23. PLOS Genetics 7(1): e1001267, Jan 2011.

Morton, E.A. and T. Lamitina: A Suite of MATLAB-based Computational Tools for Automated Analysis of COPAS Biosort Data. BioTechniques 48(6): 25-30, June 2010 Notes: NOTE - This manuscript was peer-reviewed.

J. Sznitman, Prashant K. Purohit, P. Krajacic, T. Lamitina, and P.E. Arratia: Material properties of Caenorhabditis elegans swimming at low Reynolds number. Biophysical Journal 17(98(4)): 617-26, Feb 2010.

Anne-Katrin Rohlfing , Yana Miteva , Sridhar Hannenhalli, and Todd Lamitina: Genetic and physiological activation of osmosensitive gene expression mimics transcriptional signatures of pathogen infection in C. elegans. PLOS One e9010(5(2)), Feb 2010.

Krajacic P, Hermanowski J, Lozynska O, Khurana TS, Lamitina T: The C. elegans Dysferlin homolog fer-1 is expressed in muscle and fer-1 mutations initiate altered gene expression of muscle enriched genes. Physiological genomics Sep 2009.

Lamitina, Todd. Cherry, Sara.: Dangerous liaisons: the apoptotic engulfment receptor CED-1 links innate immunity to the unfolded protein response.[comment]. Developmental Cell 15(1): 3-4, Jul 2008.

Junio AB, Li X, Massey HC Jr, Nolan TJ, Lamitina, S.T., Sundaram MV, Lok JB: Strongyloides stercoralis: cell- and tissue-specific transgene expression and co-transformation with vector constructs incorporating a common multifunctional 3' UTR. Exp Parasitol 118(2): 253-65, Feb 2008.

Huang, Chunyi George. Lamitina, Todd. Agre, Peter. Strange, Kevin.: Functional analysis of the aquaporin gene family in Caenorhabditis elegans. American Journal of Physiology - Cell Physiology 292(5): C1867-73, May 2007.

Lamitina T, Huang CG and Strange K. : Genome-wide RNAi screening identifies protein damage as a regulator of osmoprotective gene expression. Proc Natl Acad Sci U S A 103: 12173-12178, 2006.

Lamitina T.: Functional Genomic Approaches in C. elegans. Methods Mol Biol 351: 127-138, 2006.

Yan, Xiaohui. Xing, Juan. Lorin-Nebel, Catherine. Estevez, Ana Y. Nehrke, Keith. Lamitina, Todd. Strange, Kevin.: Function of a STIM1 homologue in C. elegans: evidence that store-operated Ca2+ entry is not essential for oscillatory Ca2+ signaling and ER Ca2+ homeostasis. Journal of General Physiology 128(4): 443-59, Oct 2006.

Lamitina, S Todd. Strange, Kevin.: Transcriptional targets of DAF-16 insulin signaling pathway protect C. elegans from extreme hypertonic stress. American Journal of Physiology - Cell Physiology 288(2): C467-74, Feb 2005.

Lamitina, S Todd. Morrison, Rebecca. Moeckel, Gilbert W. Strange, Kevin.: Adaptation of the nematode Caenorhabditis elegans to extreme osmotic stress. American Journal of Physiology - Cell Physiology 286(4): C785-91, Apr 2004.

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Last updated: 02/20/2014
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