Kendal Broadie
Faculty Member
Last active: 5/27/2014

Profile

I am fascinated by the development, function and adaptability of the nervous system. My research focuses on the genetic mechanisms underlying coordinated movement, behavior and cognition. How does nervous system circuitry underlying behavior develop? How are nervous system circuits modified by experience? How do these mechanisms go awry in inherited neurological diseases and age-related neurological decline? These questions center around the common themes of information transfer and information storage in cells of the nervous system. My long-term focus has been on the intercellular synapses that establish and provide communication between nerve cells. 

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I use a genetic approach in Drosophila to tackle these questions. My laboratory uses a combination of forward genetics (direct screens for mutant phenotypes), reverse genetics (targeted mutation of identified genes) and functional genomics/proteomics (genome-wide biochemical assays). Our basic strategy is to generate mutants in genes essential for synapse development or function, and then to assay mutant phenotypes as a means to elucidate the normal function of gene products. Our primary target is genes involved in establishing synapses during embryonic development (synaptogenesis), genes that mediate communication during movement and behavior (neurotransmission), or genes that maintain the developmental potential of synapses throughout life (synaptic plasticity). Synaptic development involves specifying and constructing an intercellular communication link between two cells. This developmental program specifies synaptic partnerships and aligns a presynaptic signaling field (vesicle cycling) with the postsynaptic receptor field (ligand-gated ion channels). At maturity, the function of the synapse is to translate electrical information (action potentials) into chemical information (secreted neurotransmitters) and back again. This information transfer requires mechanisms to couple an action potential to the fusion of neurotransmitter vesicles, and receipt of the signal by the receptor field. Synaptic plasticity is the process whereby synaptic structure and/or function is altered is response to this information flow (i.e. amount of use), to modulate communication either transiently (learning) or permanently (memory).  

An increasing interest in my laboratory is to develop genetic models of human neurological diseases linked to inherited synaptic dysfunction. One focus is Fragile X syndrome, the most common inherited neurological disease which results in cognitive impairment. Fragile X syndrome is caused by an arrest of synaptic development due to inappropriate translational regulation. We also study genetic models of progressive neurodegenerative diseases including Niemann-Pick C (NPC), Spastic Paraplegias and Parkinson’s Disease (PD). We are investigating the hypothesis that these diseases are caused by progressive loss of synaptic transmission, which is required to maintain neuronal viability. 

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The approach in my lab to studying nervous system development, function and plasticity is multi-disciplinary and requires the marriage of many traditionally distinct fields. The work requires classical geneticists, molecular biologists, biochemists, developmental cell biologists, anatomists and electrophysiologists. In the long term, I hope that this work will lead to a greater understanding of neural network formation, mechanisms of integrated neuronal communication, higher brain functions including learning and memory, and the cure for synaptic dysfunction arising in inherited neurological diseases.

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Developmental experience-dependent plasticity in the first synapse of the Drosophila olfactory circuit. Golovin RM, Broadie K (2016) J Neurophysiol 116(6): 2730-2738
    › Primary publication · 27683892 (PubMed) · PMC5133311 (PubMed Central)
  2. Coordinated movement, neuromuscular synaptogenesis and trans-synaptic signaling defects in Drosophila galactosemia models. Jumbo-Lucioni PP, Parkinson WM, Kopke DL, Broadie K (2016) Hum Mol Genet 25(17): 3699-3714
    › Primary publication · 27466186 (PubMed) · PMC5216615 (PubMed Central)
  3. Synaptic roles for phosphomannomutase type 2 in a new Drosophila congenital disorder of glycosylation disease model. Parkinson WM, Dookwah M, Dear ML, Gatto CL, Aoki K, Tiemeyer M, Broadie K (2016) Dis Model Mech 9(5): 513-27
    › Primary publication · 26940433 (PubMed) · PMC4892659 (PubMed Central)
  4. Neuron class-specific requirements for Fragile X Mental Retardation Protein in critical period development of calcium signaling in learning and memory circuitry. Doll CA, Broadie K (2016) Neurobiol Dis : 76-87
    › Primary publication · 26851502 (PubMed) · PMC4785039 (PubMed Central)
  5. A fully automated Drosophila olfactory classical conditioning and testing system for behavioral learning and memory assessment. Jiang H, Hanna E, Gatto CL, Page TL, Bhuva B, Broadie K (2016) J Neurosci Methods : 62-74
    › Primary publication · 26703418 (PubMed) · PMC4749449 (PubMed Central)
  6. Two classes of matrix metalloproteinases reciprocally regulate synaptogenesis. Dear ML, Dani N, Parkinson W, Zhou S, Broadie K (2016) Development 143(1): 75-87
    › Primary publication · 26603384 (PubMed) · PMC4725201 (PubMed Central)
  7. Activity-dependent FMRP requirements in development of the neural circuitry of learning and memory. Doll CA, Broadie K (2015) Development 142(7): 1346-56
    › Primary publication · 25804740 (PubMed) · PMC4378248 (PubMed Central)
  8. Overelaborated synaptic architecture and reduced synaptomatrix glycosylation in a Drosophila classic galactosemia disease model. Jumbo-Lucioni P, Parkinson W, Broadie K (2014) Dis Model Mech 7(12): 1365-78
    › Primary publication · 25326312 (PubMed) · PMC4257005 (PubMed Central)
  9. Two protein N-acetylgalactosaminyl transferases regulate synaptic plasticity by activity-dependent regulation of integrin signaling. Dani N, Zhu H, Broadie K (2014) J Neurosci 34(39): 13047-65
    › Primary publication · 25253852 (PubMed) · PMC4172800 (PubMed Central)
  10. Impaired activity-dependent neural circuit assembly and refinement in autism spectrum disorder genetic models. Doll CA, Broadie K (2014) Front Cell Neurosci : 30
    › Primary publication · 24570656 (PubMed) · PMC3916725 (PubMed Central)
  11. GABAergic circuit dysfunction in the Drosophila Fragile X syndrome model. Gatto CL, Pereira D, Broadie K (2014) Neurobiol Dis : 142-59
    › Primary publication · 24423648 (PubMed) · PMC3988906 (PubMed Central)
  12. N-glycosylation requirements in neuromuscular synaptogenesis. Parkinson W, Dear ML, Rushton E, Broadie K (2013) Development 140(24): 4970-81
    › Primary publication · 24227656 (PubMed) · PMC3848190 (PubMed Central)
  13. Fragile X mental retardation protein regulates trans-synaptic signaling in Drosophila. Friedman SH, Dani N, Rushton E, Broadie K (2013) Dis Model Mech 6(6): 1400-13
    › Primary publication · 24046358 (PubMed) · PMC3820263 (PubMed Central)
  14. miR-153 regulates SNAP-25, synaptic transmission, and neuronal development. Wei C, Thatcher EJ, Olena AF, Cha DJ, Perdigoto AL, Marshall AF, Carter BD, Broadie K, Patton JG (2013) PLoS One 8(2): e57080
    › Primary publication · 23451149 (PubMed) · PMC3581580 (PubMed Central)
  15. The cell polarity scaffold Lethal Giant Larvae regulates synapse morphology and function. Staples J, Broadie K (2013) J Cell Sci 126(Pt 9): 1992-2003
    › Primary publication · 23444371 (PubMed) · PMC3666253 (PubMed Central)
  16. A targeted glycan-related gene screen reveals heparan sulfate proteoglycan sulfation regulates WNT and BMP trans-synaptic signaling. Dani N, Nahm M, Lee S, Broadie K (2012) PLoS Genet 8(11): e1003031
    › Primary publication · 23144627 (PubMed) · PMC3493450 (PubMed Central)
  17. Jelly Belly trans-synaptic signaling to anaplastic lymphoma kinase regulates neurotransmission strength and synapse architecture. Rohrbough J, Kent KS, Broadie K, Weiss JB (2013) Dev Neurobiol 73(3): 189-208
    › Primary publication · 22949158 (PubMed) · PMC3565053 (PubMed Central)
  18. Matrix metalloproteinases and minocycline: therapeutic avenues for fragile X syndrome. Siller SS, Broadie K (2012) Neural Plast : 124548
    › Primary publication · 22685676 (PubMed) · PMC3364018 (PubMed Central)
  19. Structure-function analysis of endogenous lectin mind-the-gap in synaptogenesis. Rushton E, Rohrbough J, Deutsch K, Broadie K (2012) Dev Neurobiol 72(8): 1161-79
    › Primary publication · 22234957 (PubMed) · PMC3417755 (PubMed Central)
  20. In vivo neuronal function of the fragile X mental retardation protein is regulated by phosphorylation. Coffee RL, Williamson AJ, Adkins CM, Gray MC, Page TL, Broadie K (2012) Hum Mol Genet 21(4): 900-15
    › Primary publication · 22080836 (PubMed) · PMC3263990 (PubMed Central)
  21. Extracellular matrix and its receptors in Drosophila neural development. Broadie K, Baumgartner S, Prokop A (2011) Dev Neurobiol 71(11): 1102-30
    › Primary publication · 21688401 (PubMed) · PMC3192297 (PubMed Central)
  22. Neural circuit architecture defects in a Drosophila model of Fragile X syndrome are alleviated by minocycline treatment and genetic removal of matrix metalloproteinase. Siller SS, Broadie K (2011) Dis Model Mech 4(5): 673-85
    › Primary publication · 21669931 (PubMed) · PMC3180232 (PubMed Central)
  23. Drosophila modeling of heritable neurodevelopmental disorders. Gatto CL, Broadie K (2011) Curr Opin Neurobiol 21(6): 834-41
    › Primary publication · 21596554 (PubMed) · PMC3172335 (PubMed Central)
  24. Fragile X mental retardation protein is required for programmed cell death and clearance of developmentally-transient peptidergic neurons. Gatto CL, Broadie K (2011) Dev Biol 356(2): 291-307
    › Primary publication · 21596027 (PubMed) · PMC3143227 (PubMed Central)
  25. Glycosylated synaptomatrix regulation of trans-synaptic signaling. Dani N, Broadie K (2012) Dev Neurobiol 72(1): 2-21
    › Primary publication · 21509945 (PubMed) · PMC3240703 (PubMed Central)
  26. Drosophila rolling blackout displays lipase domain-dependent and -independent endocytic functions downstream of dynamin. Vijayakrishnan N, Phillips SE, Broadie K (2010) Traffic 11(12): 1567-78
    › Primary publication · 21029287 (PubMed) · PMC2975403 (PubMed Central)
  27. Anterograde Jelly belly ligand to Alk receptor signaling at developing synapses is regulated by Mind the gap. Rohrbough J, Broadie K (2010) Development 137(20): 3523-33
    › Primary publication · 20876658 (PubMed) · PMC2947762 (PubMed Central)
  28. The fragile X mental retardation protein developmentally regulates the strength and fidelity of calcium signaling in Drosophila mushroom body neurons. Tessier CR, Broadie K (2011) Neurobiol Dis 41(1): 147-59
    › Primary publication · 20843478 (PubMed) · PMC2982942 (PubMed Central)
  29. The nonsense-mediated decay pathway maintains synapse architecture and synaptic vesicle cycle efficacy. Long AA, Mahapatra CT, Woodruff EA, Rohrbough J, Leung HT, Shino S, An L, Doerge RW, Metzstein MM, Pak WL, Broadie K (2010) J Cell Sci 123(Pt 19): 3303-15
    › Primary publication · 20826458 (PubMed) · PMC2939802 (PubMed Central)
  30. Fragile X mental retardation protein has a unique, evolutionarily conserved neuronal function not shared with FXR1P or FXR2P. Coffee RL, Tessier CR, Woodruff EA, Broadie K (2010) Dis Model Mech 3(7-8): 471-85
    › Primary publication · 20442204 (PubMed) · PMC2898537 (PubMed Central)