Dr. Patrick Nahirney

Dr. Patrick Nahirney
Position
Associate Professor, Neuroscience
Credentials

BSc (Wash St), MSc (UBC), PhD (UBC)

Contact
Office: Medical Sciences Building, room 220

Dr. Patrick Nahirney is an Associate Professor of Anatomy and Histology in the Division of Medical Sciences. He teaches human gross anatomy and histology to first and second year undergraduate medical students in the Island Medical Program and conducts research on neurogenesis and neuromuscular disease. He has a particular interest in providing a structural and molecular framework that relates to a number of human diseases including Alzheimer's disease, stress-induced memory loss, Nemaline myopathy, Duchenne muscular dystrophy as well as the development of novel strategies for muscle and nerve tissue engineering and regeneration of injured tissues.

"The goal is to understand how stressors and neurological diseases impact learning and memory processes."

Graphic

Synapses in the brain play key roles in neuronal communication and altered synaptic function is believed to underlie a number of neurological disorders.

It has long been known that the hippocampus plays a role in learning and memory – it has become of extreme interest since changes in pyramidal, granule, interneuronal and glial cells occur in response to stressors, diseases and experimental treatments, and correspond to changes in spatial learning and memory.

Surprisingly, however, data is lacking on the specific subcellular structure of synapses in the hippocampus, and the changes that occur at the level of the synapse to various stressors and treatments.

This research examines how maternal stress and ethanol affect in utero and postnatal development of synapses in the hippocampus. Clinical evidence in humans suggests a strong link between prenatal stress and childhood disorders such as autism, fetal alcohol syndrome and schizophrenia.

To further these studies, my research will also test how exercise can reverse the effects caused by these stressors during postnatal life. Data from this research will shed new light on how prenatal stress affects synapses made by hippocampal neurons and will provide a testable model system to ascertain the effectiveness of treatments for these neurological disorders.

Shown above is a high magnification transmission electron micrograph of a branched spine making two synaptic contacts (*) with presynaptic terminals. The spine and dendrite of the postsynaptic granule cell neuron have been pseudocolored red. Vesicles containing neurotransmitters fill the presynaptic terminals. x50000.

Mito: mitochondria, MT: microtubule, Pre: Presynaptic terminal, SER: Smooth endoplasmic reticulum

"The overall aim of the research is to develop therapies to promote growth and repair of muscle tissue"

A major question that remains unanswered in muscle development is the mechanism that controls myoblast fusion and how myoblasts recognize each other during fusion competency.

The remodeling of cytoplasmic elements that precedes fusion, including the cytoskeleton, organelles and nuclei, and cell surface recognition sites, are all critical for the ultimate fusion and formation of a multi-nucleated skeletal muscle fiber.

This aspect of my research explores fusion mechanisms in cultured myoblast cells by live-cell multi-channel fluorescence imaging with fluorescent probes and correlative serial sectin electron microscopy to elucidate the molecular and ultrastructural properties of fusion as it ensues in developing and regenerating muscle.

A second aspect of the muscle project will examine the later stages of muscle grwoth known as myofibrillogenesis. Hypertrophic growth of the myotube through the assembly of myofilaments into myoibrils is necessary to enhance contractile force to meet the functional demands associated with postnatal life.

This is a fundamental growth process of muscle that can be modified by changes in physical deformation of the developing myotube (i.e. stretch). Using the in vitro model system, muscle myotubes will be subjected to linear cyclical changes on a flexible substrate and recorded by live-cell microscopy.

These myotubes will be subsequently examined in detail using immunocytochemistry and electron microscopy, and muscle gene and protein expression patterns will be studied at specific time points by PCR and Western blot analysis.

Shown above are phase contrast light microscopic images from a live-cell imaging series revealing the formation  of a multinucleated myotube (right panel) from muscle precursor cells known as myoblasts (left panel). This fusion process relies on a comples pattern of extracellular cues and intracellular remodeling mechanisms.

Research articles
  1. Nahirney, P.C., P. Reeson and C. E. Brown 2016 Ultrastructural analysis of blood-brain barrier breakdown in the peri-infarct zone in young adult and aged mice.  Journal of Cerebral Blood Flow and Metabolism, 36(2): 413-25. PUBMED.
  2. Reeson, P., K. Tennant, K. Gerrow, J. Wang, S. Novak, K. Thompson, K. Lockheart, A. Holmes, P.C. Nahirney and C.E. Brown 2015 Delayed inhibition of VEGF signaling after stroke attenuates blood-brain barrier breakdown and improves functional recovery in a comorbidity-dependent manner.  Journal of Neuroscience, Apr 1; 35(13):5128-43 (cover image). PUBMED
  3. Lindsay, F.J., A.R. Patten, B.R. Christie and P.C. Nahirney 2014 Prenatal ethanol exposure reduces pyramidal cell size and postsynaptic density length in the CA1 region of the hippocampus in adolescent rats. FASEB Journal. Vol 21;726.2.
  4. Novak, S.W., M. Vetrici, C.R. King, J. Boots, B.R. Christie and P.C. Nahirney 2013 Developmental changes to dentate gyrus PSD-95 expression and dendritic spine ultrastructure in a mouse model of Fragile X Syndrome. Society of Neuroscience Vol. 43.
  5. Nahirney, P.C., P. Reeson, C.E. Brown 2013 Ultrastructral analysis of neurons, glia and capillaries in the peri-infarct zone of an ischemic stroke. FASEB J. Vol 20; 533.15.
  6. Brown, C.E., D. Sweetnam, M. Beange, P.C. Nahirney and R. Nashmi 2012 α4* nicotinic acetylcholine receptors modulate experience-based cortical depression in the adult mouse somatosensory cortex. Journal of Neuroscience, 32(4): 1207-19. PUBMED
  7. Samson J., I. Piscopo, A. Yampolski, P.C. Nahirney, A. Parpas, A. Aggarwal, R. Saleh and C.M. Drain 2011 fabrication of size-tunable metallic nanoparticles using plasmid DNA as a biomolecular reactor. Nanomaterials, 1(1):64-78.
  8. Samson J., P.C. Nahirney, D.M. Drain and I. Piscopo 2011 Simplifying electron diffraction pattern identification of mixed-material nanoparticles. Microscopy Today, 19:38-41
  9. Nowak, S.J., P.C. Nahirney, K. Hadjantonakis and M.K. Baylies. 2009 Live imaging reveals actin cytoskeleton remodeling is essential for mammalian myoblast fusion. Journal of Cell Science, 122: 3282-93. PUBMED
  10. Samson, J., A. Varotto, P.C. Nahirney, A. Toschi, I. Piscopo and C.M. Drain. 2009 Fabrication of metal nanoparticles using toroidal plasmid DNA as a sacrificial mold. ACS Nano, 3(2): 339-344. PUBMED
  11. Nahirney, P.C., J.G. Forbes, H.D. Morris, S.C. Chock and K. Wang. 2006 What the buzz was all about: Superfast song muscles rattle the tymbals of male cicadas. FASEB Journal, 20:2017-26. PUBMED
  12. Nahirney, P.C., D.A. Fischman and K. Wang 2006 Myosin flares and actin leptomeres as myofibril assembly/disassembly intermediates in sonic muscle fibers. Cell and Tissue Research, 324: 127-138. PUBMED
  13. Xaymardan, M.,L. Tang, L. Zagreda, B. Pallante, J. Zheng, J.L. Chazen, A. Chin, I. Duignan, P. Nahirney, S. Rafii, T. Mikawa and J.M. Edelberg 2004 Platelet-derived growth factor-AB promotes the generation of adult bone marrow-derived cardiac myocytes. Circulation Research, 94: e39-e45. PUBMED
  14. Lewis, M.K., P.C. Nahirney, V. Chen, B.B. Adhikari, J. Wright, M.K. Reedy, A.H. Bass and K. Wang 2003 Concentric intermediate filament lattice links to specialized Z-band junctional complexes in sonic muscle fibers of the type I male midshipman fish. Journal of Structural Biology, 143(1): 56-71. Cover illustration. PUBMED
  15. Nahirney, P.C., T. Mikawa and D.A. Fischman 2003 Evidence for an extracellular matrix bridge guiding proepicardial cell migration to the myocardium of chick embryos. Developmental Dynamics, 227: 511-523. Cover illustration. PUBMED
  16. *Zippin, J.H., Y. *Chen, *P. Nahirney, M. Kamenetsky, M.S. Wuttke, D.A. Fischman, L.R. Levin, and J. Buck 2003 Compartmentalization of bicarbonate-sensitive adenylyl cyclase in distinct signaling microdomains. FASEB Journal, 17: 82-84. Cover illustration. *First three authors contributed equally. PUBMED
  17. Klimuk S.K., S.C. Semple, P.C. Nahirney, M.C. Mullen, C.F. Bennett, P. Scherrer and M.J. Hope 2000 Enhanced anti-inflammatory activity of a liposomal intercellular adhesion molecule-1 antisense oligodeoxynucleotide in an acute model of contact hypersensitivity. Journal of Pharmacology and Experimental Therapeutics, 292: 480-488. PUBMED
  18. Jiang X., T. Kobayashi, P.C. Nahirney, E. Garcia del Saz and H. Seguchi 2000 Ultracytochemical study on the localization of superoxide producing sites in stimulated rat neutrophils. Anatomical Record, 258: 156-165. PUBMED
  19. Ovalle, W.K., P.R. Dow and P.C. Nahirney 1999 Structure, distribution, and innervation of muscle spindles in avian fast and slow skeletal muscle. Journal of Anatomy, 194: 381-394. PUBMED
  20. Ovalle, W.K., S.L. Shinn and P.C. Nahirney 1998 Ultrastructure of the larval tentacle and its skeletal muscle in Xenopus laevis. Tissue & Cell, 30: 216-225. PUBMED
  21. Jiang, X., T. Kobayashi, P.C. Nahirney, E. Garcia del Saz and H. Seguchi 1998 An ultracytochemical study on the dynamics of alkaline phosphatase-positive granules in rat neutrophils. Histology and Histopathology, 13: 57-65.
  22. Kamada, M., T. Kobayashi, P.C. Nahirney, T. Okada, E. Garcia del Saz, T. Shuin and H. Seguchi 1997 Actin and cytokeratin in superficial transitional epithelial cells of the rabbit urinary bladder: A confocal and electron microscopic study. Acta Histochemica et Cytochemica, 30: 29-36. PUBMED
  23. Nahirney, P.C., P.R. Dow and W.K. Ovalle 1997 Quantitative morphology of mast cells in skeletal muscle of normal and genetically-dystrophic mice. Anatomical Record, 247: 341-349. PUBMED
  24. Jiang, X., T. Kobayashi, P.C. Nahirney, E. Garcia del Saz and H. Seguchi 1996 Ultracytochemical localization of alkaline phosphatase (ALPase) activity in neutrophils of the rat lung following injection of lipopolysaccharide. Acta Anatomica Nipponica, 71: 183-194. PUBMED
  25. Nahirney, P.C. and W.K. Ovalle 1993 Distribution of dystrophin and neurofilament protein in muscle spindles of normal and mdx-dystrophic mice: An immunocytochemical study. Anatomical Record, 235: 501-510. PUBMED
Book and educational materials
  1. Ovalle, W.K. and P.C. Nahirney Netter's Essential Histology. Second Edition. Elsevier/Saunders, Philadelphia, PA, 2008 (ISBN: 978-1-4557-0631-0), 517 pages.
  2. Ovalle, W.K. and P.C. Nahirney Netter's Histology Flash Cards. Second Edition. Elsevier/Saunders, Philadelphia, PA, 2008 (ISBN: 978-1-4160-4629-5), 223 cards.
  3. Ovalle, W.K. and P.C. Nahirney Netter’s Essential Histology. Elsevier/Saunders, Philadelphia, PA, 2008 (ISBN: 978-1-929007-86-8), 493 pages.
  4. Ovalle, W.K. and P.C. Nahirney Netter’s Histology Flash Cards. Elsevier/Saunders, Philadelphia, PA, 2008 (ISBN: 978-1-4160-4629-5), 223 cards.
Translated book versions
  1. Ovalle, W.K. and P.C. Nahirney Netter’s Essential Histology. Portuguese translation. Elsevier/Saunders, Philadelphia, PA, 2008 (ISBN: 978-85-352-2803-8), 493 pages.
  2. Ovalle, W.K. and P.C. Nahirney Netter’s Essential Histology. Turkish translation. Elsevier/Saunders, Philadelphia, PA, 2009 (ISBN: 978-975-277-220-5), 486 pages.
  3. Ovalle, W.K. and P.C. Nahirney Netter’s Essential Histology. Korean translation. Elsevier/Saunders, Philadelphia, PA, 2009 (ISBN: 978-89-92589-59-8), 491 pages.
  4. Ovalle, W.K. and P.C. Nahirney. Netter's Essential Histology. Greek translation. Elsevier/Saunders, Philadelphia, PA, 2011 (ISBN: 978-960-489-088-0) 500 pages.
Online educational materials  
  1. Ovalle, W.K. and P.C. Nahirney Netter's Essential Histology Video Series on Student Consult (www.studentconsult.com)
  2. Ovalle, W.K. and P.C. Nahirney Netter’s Essential Histology on Student Consult (www.studentconsult.com).
  3. Ovalle, W.K. and P.C. Nahirney EM (Electron Microscopy) Magnifier, University of British Columbia (http://em.anat.ubc.ca).

Past Graduate Students

Sammy Weiser Novak, MSc. (Apr 2015)

Thesis entitled: Ultrastructure and Morphometric analysis of Hippocampal Synapses in the Fmr1-/y Mouse Model of Fragile X Syndrome

Jessica Bilkey, MSc. (Apr 2015)

Thesis entitled: Modulation of Synaptic Vesicle Polls by Serotonin and the Spatial Organization of Vesicle Pools at the Crayfish Opener Neuromuscular Junction

Matthew Grey, MSc.

Thesis entitled: Bio-engineering of Muscle Tissue in Culture: Influence of Neural, Cartilage or Kidney Cells and the Effect of Retinoic Acid on Muscle Cell Growth.

December 2011

Past Honours Students

Caitlin King, BSc. (Honours)

Thesis entitled: Ultrastructure of Synapses in the Dentate Gyrus of the Mouse Model of Fragile X Syndrome.

May 2010


Natural Sciences and Engineering Research Council of Canada (NSERC)

125K NSERC Discovery Grant for a five-year study of the effects of prenatal stress on synapse ultrastructure. This project focuses on brain development and function from a structural perspective by utilizing electron microscopic imaging to pinpoint alterations in synapses and neurons.

Canada Foundation for Innovation (CFI) and BC Knowledge and Development (BCKDF)

$375K CFI- BCKDF Leaders Opportunity Fund used for the purchase of a new transmission electron microscope.

Electron Tomography - Synapse in Dentate Gyrus

Soleus muscle cross-section by LM

Serial cryosections of the soleus muscle from the mouse stained with hematoxylin and eosin (H&E), acid-stable myofibrillar ATPase (reveals fiber types) and with NADH-tetrazolium reductase (reveals mitochondrial density within fibers). A muscle spindle (neuromuscular receptor in muscle) is seen in the upper right.

TEM of Primary myotube in culture

Transmission electron micrograph of a day 10 differentiated primary muscle cell culture (from mouse) showing a myotube with laterally fusing myoblasts. Low and medium magnification views of the fusing myoblasts and developing (nascent) myofibrils are shown (from x500 to x2000).

Muscle cell fusion

Time-lapse live-cell imaging video illustrating a key event in myogenesis and highlighting the interplay of myoblasts and myotubes during muscle development. Images were captured at five minute intervals over a period of 10 hrs. Fusion relies on a complex pattern of extracellular cues and intracellular remodeling mechanisms.

Myoblasts in growth phase

Time-lapse live-cell imaging video of L6 myoblasts in growth medium growing on plastic. An uncommonly seen trinary (ternary) division occurs in a parent cell in the field of view. Images were captured at 3 minute intervals.

Glial cell TEM zoom series

Cultured glial cell viewed by transmission electron microscopy. This cell shows an impressive array of cytoplasmic elements, organelles and nuclear pores. The file contains multiple images from low to high magnification (from x5000 to x50000).

Sonic muscle fiber schematic

Three-dimensional rendering of the high performance muscle fiber in the type 1 male singing toadfish (midshipman). The male fish uses these specialized muscle fibers to vibrate the swimbladder and produce a humming sound that attracts females during the mating season. This specialized muscle can contract and relax approximately 100 times per second for up to two hours.

Electron tomography - Virus particles inside cell

Tilt series of an HIV infected cell in culture. Images were captured at 5 degree tilt intervals over an arc of 70 degrees. This work was done in collaboration with Dr. Yang Luo at Rockefeller University.