Alexander JaworskiAssistant Professor of Neuroscience
Alex Jaworski obtained a Master's degree in Biochemistry at the Free University of Berlin in Germany. He completed his PhD in Developmental Genetics at New York University where he studied neuromuscular synapse formation under Dr. Steven J. Burden. During his postdoctoral training in axon guidance with Dr. Marc Tessier-Lavigne, he worked at the biotechnology company Genentech and at Rockefeller University. Dr. Jaworski joined the faculty at Brown in July 2013.
Jaworski A, Tom I, Tong RK, Gildea HK, Koch AW, Gonzalez LC, Tessier-Lavigne M (2015) Operational redundancy in axon guidance through the multifunctional receptor Robo3 and its ligand NELL2. Science 350(6263):961-965
Olsen O, Kallop D, McLaughlin T, Huntwork-Rodriguez S, Wu Z, Duggan CD, Simon DJ, Lu Y, Easley-Neal C, Takeda K, Hass PE, Jaworski A, O’Leary DD, Weimer RM, Tessier-Lavigne M (2014) Genetic analysis reveals that Amyloid Precursor Protein and Death Receptor 6 function in the same pathway to control axonal pruning independent of beta-secretase. J Neurosci 34(19):6438-6447. PMID: 24806670
Zhang B, Xiao W, Qiu H, Zhang F, Moniz, HA, Jaworski A, Condac E, Gutierrez-Sanchez G, Heiss C, Clugston RD, Azadi P, Greer JJ, Bergmann C, Moremen KW, Li D, Linhardt RJ, Esko JD, Wang L (2013) Heparan sulfate deficiency disrupts developmental angiogenesis and causes congenital diaphragmatic hernia. J Clin Invest 124(1):209-221. PMID: 24355925
Jaworski A, Tessier-Lavigne M (2012) Autocrine/juxtaparacrine regulation of axon fasciculation by Slit-Robo signaling. Nat Neurosci 15(3):367-369. PMID: 22306607
Jaworski A, Long H, Tessier-Lavigne M (2010) Collaborative and specialized functions of Robo1 and Robo2 in spinal commissural axon guidance. J Neurosci 30(28):9445-9453. PMID: 20631173
Jaworski A, Smith CL, Burden SJ (2007) GA-binding protein is dispensable for neuromuscular synapse formation and synapse-specific gene expression. Mol Cell Biol 27(13): 5040-5046. PMCID: PMC1951497
Jaworski A, Burden SJ (2006) Neuromuscular synapse formation in mice lacking motor neuron- and skeletal-muscle-derived Neuregulin-1. J Neurosci 26(2):655-661. PMID: 16407563
Jevsek M, Jaworski A, Polo-Parada L, Kim, N, Fan J, Landmesser LT, Burden SJ (2006) CD24 is expressed by myofiber synaptic nuclei and regulates synaptic transmission. Proc Natl Acad Sci USA 103(16): 6374-6379. PMCID: PMC1435367
My laboratory studies the molecular and cellular mechanisms of brain wiring. The mature nervous system contains billions of neurons that are interconnected in a highly specific manner and communicate through trillions of synapses. We are interested in understanding how this complex wiring pattern is established during embryonic development. To this end we employ a variety of experimental approaches, including molecular biology, biochemistry, embryology, and mouse genetics.
To produce a functional nervous system, neurons must form precise connections with each other during embryonic development. One important aspect of this wiring process is the guidance of developing axons to their correct targets. This process of axon pathfinding is mediated by molecular cues that activate receptors in the leading process of the axon, the growth cone, to attract or repel nascent axons. Axons navigate through intermediate targets to reach their final destinations and must switch from attraction to repulsion when passing an intermediate target. To understand brain wiring, it is crucial to define the full repertoire of axon guidance cues and receptors, determine how these molecules regulate growth cone turning, and identify mechanisms that allow axons to modulate their responses to guidance cues. Insights into neural circuit development can help elucidate the basis of diseases resulting from brain mis-wiring. Moreover, manipulating guidance pathways and the growth state of axons in the adult central nervous system has the potential to allow for the restoration of neuronal connections after physical injury or onset of neurodegenerative disease.
My lab is interested in understanding how axons find their targets and form connections with the correct synaptic partners during development. We use biochemistry (e.g. protein interaction assays, fractionation) to identify novel axon guidance molecules and characterize these cues and downstream signal transduction events using cell and tissue culture assays that allow us to study axonal responses in vitro. We combine these approaches with mouse genetics and embryological experiments (e.g. targeted delivery of expression constructs in embryos developing ex utero) that allow molecular manipulations in the in vivo context of the developing nervous system.