Faculty Profile: Alexander Jaworski, Ph.D., New York University

Alexander Jaworski
Alexander Jaworski, Ph.D., New York University
Assistant Professor of Neuroscience
Bio Med Neuroscience
Work: +1 401-863-1963
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.

Biography

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 under supervision of Dr. Steven J. Burden studying neuromuscular synapse formation. 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.

Research Description

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 are sensed by receptors in the leading process of the axon, the growth cone. Over the past two decades, considerable progress has been made in the identification of the molecular cues that attract or repel axons and the receptors mediating these effects, but many questions remain. What is the full repertoire of axon guidance molecules? What signaling mechanisms connect guidance cues to cytoskeletal changes in the growth cone? How do different guidance factors interact with each other, and what determines how a growth cone responds to multiple, sometimes contradictory, guidance cues?

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. My lab also studies how axons integrate and/or choose between multiple cues during pathfinding and target selection. As an axon navigates through the embryo, it is exposed to a number of guidance molecules, both simultaneously and successively. Hence, axons must modulate their responses to guidance cues depending on which part of their overall trajectory they are on, ignoring some cues while responding to others. Similarly, when entering their target fields, axons must switch from guidance responses to synaptogenic responses. Insight into how axons can make these adjustments and identifying points of cross-talk between guidance cues is central to understanding nervous system wiring. Importantly, 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.

Affiliations

Society for Neuroscience
New York Academy of Sciences

Selected Publications

  • 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 (2013)
  • Jaworski A, Tessier-Lavigne M (2012) Autocrine/juxtaparacrine regulation of axon fasciculation by Slit-Robo signaling. Nat Neurosci 15(3):367-369. PMID: 22306607 (2012)
  • 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 (2010)
  • 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 (2007)
  • 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 (2006)
  • 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 (2006)