The Isaac Skeeles you mention probably is my ancestor, who was born 2 Jun 1786 in MD and came to what is now Carroll Co, then to Tuscarawas Co, OH. (Carroll Co. was formed in 1833 from parts of Columbiana, Stark, Harrison, Jefferson, and Tuscarawas Cos.; Tuscarawas was formed in 1808 from Muskingum). A family story says Isaac was of English descent, the son of a British soldier who "changed sides." Isaac also apparently fought in the War of 1812. Family history says that the name originally was Danish (from a family that emigrated from Denmark to England) and was spelled "Skeel."
The second husband of Isaac's oldest daughter, Jane, was William Asbury Herron, who was originally from Baltimore Co., MD.
I have no other information on Isaac's origins, but it seems very likely that he and William were related.
I have seen the name Nicholas Skeeles mentioned as an early settler in Ohio, but have not been able to find anything else on him.