Research

Our lab is studying how cells regulate their own proliferation, developing potential therapeutics for fibrosing diseases such as pulmonary fibrosis, and elucidating how cells can be induced to move away from a location, such as inducing neutrophils to not enter and/or leave the lungs in acute respiratory distress syndrome (ARDS), a disease where too many neutrophils enter the lungs and cause extensive lung damage.

Current projects

  1. Identify signals that Dictyostelium cells secrete to slow or stop their own proliferation, and determine the signal transduction pathways used by these signals to slow or stop proliferation.
  1. Determine what regulates the differentiation of some white blood cells into scar tissue, and use this information to prevent the scar tissue formation in fibrosing diseases.
  1. Elucidate how a factor acts as a chemorepellent, leading to potential therapeutics for neutrophil-driven diseases such as acute respiratory distress syndrome, rheumatoid arthritis, and pressure and venous ulcers.

Past projects

Cell-cycle Dependent Initial Cell-type choice
When an embryo starts growing, how do the cells decide what type of cell to become (bone, muscle, nerve, etc.)?  We found a simple and elegant mechanism that lets a population of cells break symmetry and differentiate into separate cell types.

Cell Density Sensing
After a mechanism such as the one described above generates different cell types, how does the system sense the relative proportions of the different cell types?  We found that by using secreted signals, cells can sense the composition of a tissue that contains a variety of cell types.

Cell Number Counting
After a tissue forms, with the composition of the tissue regulated by the two mechanisms described above, what regulates the size of a tissue?  A secreted signal can be used to sense the number of cells in a group.  If the group is too large, the signal can either stop cell proliferation or, by increasing random motility and/or decreasing adhesion, cause the group to break into smaller groups. We used a combination of genetics, biochemistry, and computer simulations to uncover a simple and elegant mechanism that developing Dictyostelium cells use to form groups of ~20,000 cells.

Exotic Star Binaries
Accretion disks are made of gas orbiting and falling into a central mass.  Disks are found around the central massive black hole in quasars.  When a disk forms around a star, it can condense into planets.  In collaboration with Dr. Keith Horne of the University of St. Andrews, we studied the flow of gas in accretion disks in binary star systems when the accreting object is a white dwarf, neutron star, or black hole.

TNF-α and cumulus cell-oocyte complex expansion
Ovulation is the process by which a fertilizable oocyte and surrounding somatic cumulus cells (the cumulus cell-oocyte complex; COC) are released form the ovary for fertilization.  The microenvironment and selected signaling events within the COC of preovulatory follicles are essential for proper formation of an extracellular matrix critical for ovulation.  This area links to videos showing that blocking the activity of the TSG-6 link module disrupts normal COC expansion.

Shotgun Antisense
We developed a widely-applicable genetic tool we called shotgun antisense that allows us to identify an interesting mutant in the morning, and start sequencing the gene’s DNA in the afternoon.