in my lab focuses on the repair of damaged DNA, specifically damage
encountered during active replication or S-phase. DNA is a
dynamic biopolymer that contains the genetic information for
life. The accurate copying of this information is critical to
survival yet the DNA is constantly damaged from the byproducts of
metabolism within a cell as well as from exposure to toxins in the
environment. The state of persistent DNA damage leads to
undesired genetic changes, perhaps even cancer. Therefore, cells
have devised numerous pathways for the repair of DNA damage. Research
in my lab explores the interaction between two known DNA damage repair
proteins, Bloom syndrome protein (Blm) and Rad51.
Undergraduate research in my lab is critical for success. Individual projects include:
subcloning of cDNA for the full-length Blm protein as well as specific
deletion mutants that will assist in determining the exact residues
that contact Rad51
*The over expression and purification of Blm proteins to be used for in vitro biochemical assays
*Determining Protein-Protein binding interactions again to be used to assess the affect of deletion mutants
This work is supported by the RI-INBRE grant for the NIH.
Williams’ research group is actively involved in the synthesis,
analysis, and toxicity screening of arylphosphonium salts. This type of
compound readily passes the cell membrane and the mitochondrial
membrane. They complex with DNA in vitro and are inhibitors of acetylcholinesterase, both in vitro and in vivo. The literature reports anti-parasitic and anti-cancer activity in vivo for some of these molecules. They are also antibacterials.
long-term goal is to prepare novel compounds of this class that will
show selective toxicity against bacteria, especially resistant strains,
selective inhibition of acetylcholinesterase, which is one approach to
treatment of Alzheimer’s Disease, and selective binding of DNA in
malignant cells and thereby act as a cancer chemotherapeutic agents.
current research projects introduce chemistry and biology students to
the essentials of drug development research: make the compounds,
collect ADMET data, screen the compounds, select the active compounds
for in vivo testing. A parallel project is computational chemistry (see Theoretical Chemistry) of these salts as potential DNA and protein binders.
This work is supported by the RI College Faculty Research Fund, EPSCoR and RI-INBRE