Biological researches: from membrane-bound bacteriophage, to electric fish & synaptic receptors, intermediate filaments, gene regulation, mesoderm and neural creest specification & induction

By way of introduction:

My scientific career began at Penn State, where I worked as an independent study student with Wally Snipes and Alec Keith.


My project was to study the effects of adamantanone on the assembly of the membrane-bound bacterial virus PM2

Turns out adamantanone blocked PM2 assembly.


In graduate school, I did my thesis work with Bob Stroud (CalTech/UCSF) on the structure of the nicotinic acetylcholine receptor, isolated from the electric organ of Torpedo californica.
** PLEASE DESCRIBE THIS IMAGE ** This introduced me to structural methods & electron microscopy.

After receptors, I began a Muscular Dystrophy Association post-doc with Martin Raff (UC London).

After some futile attempts to clone neural precursors, I started working on the functional roles of intermediate filaments, first on the vimentin-filament system of fibroblasts and later, with Birgitte Lane, on the keratin-type filament systems of epithelial cells.



This was interesting introduction into the world of experimental cell biology, as well as the sociology of science; particularly how different fields "work".

I then moved to New York, and worked with Lee Rubin (Rockefeller University) on synaptic clutering of acetylcholine receptor and esterase in cultured muscle.

One cannot underestimate Lee's patience with me, as I was in a traumatized state!!!

I then moved on to take a position in MCD Biology, UC Boulder - where I have been ever since!

At Boulder, I first initially focussed on the control of intermediate filament organization, specifically in the context of the human disease Giant Axonal Neuropathy. With Dorothy Plummer, an undergraduate, we discovered that in at least two human GAN fibroblast lines, the bundled IF phenotype was dependent on serum levels. In response to the claim that acrylamide could be used as a specific disruptor of IF organization, I went on to show that a wide range of metabolic and protein synthesis inhibitors disrupted intermediate filament organization.

This led us to begin studies in intermediate filaments in an organismic context, the clawed frog Xenopus laevis.

GAN serum effect

sox placode

These studies were greatly facilitated by the work on some great graduate students:

  • Joe Dent studied vimentin-type IFs (and developing a whole-mount staining method for Xenopus embryos;
  • Jeff Bachant, worked out the dynamics of keratin organization in the maturing oocyte;
  • Dan Chu who characterized the expression of acetylated tubulin in the early embryo;
  • Robert Cary characterized desmin function through correlative fluorescence microscopy and ultrastructural studies;
  • David Shook worked with me on the role of keratins in gastrulation; and
  • Tim Carl,a graduate student with Jim Hanken, worked Chris Dufton (a graduate student) on the role of Slug (Snail2) in neural crest formation, and
  • Dan Seufert, a graduate student with Jim Hanken, on type II collagen expression in Xenopus and Eleutherodactylus (a direct-developing frog).

During this time, I also had a great technician, Laurie Maynell who worked both on keratin reorganization in the early embryo (with Andy Polson, an undergraduate and Cory Nislow a rotation student, if I remember correctly), the role of keratins in gastrulation, and together with Karla Kirkegaard on the inhibition of poliovirus regulation by brefelding A.

We were then joined by Alla Karnovsky, a post doc, who worked on the role of plakoglobin (gamma-catenin) as a regulator of Wnt Signaling. John Merriam (a technician) and Adam Rubinstein (an undergraduate student), together with Yanni Vourgourakis (a graduate students) also worked on aspects of plakoglobin-wnt signaling. This led to collaborations with Grant Barish and Bart Williams (members of Harold Varmus's lab) and Aaron Zorn on Sox inhibition of beta-catenin mediated wnt signaling.

This was followed by studies with Chi Zhang on Soxs and Snail2 and Jianli Shi on Snail2 and Centrin (which is were are current efforts are focussed.

last revised - 18-Oct-2012