Sure! Head over to the app Preferences, and add one or more characters. When you hit any of those characters, the app will start listening to your keystrokes and enable text expansion if a shortcut matches what you are typing.
For instance, if you use / as a shortcut, typing /eml will be the way to get your email address with the shortcut eml.
No, you can remove all characters. In that case, typedesk will always listen to your keystrokes and try to match your response shortcuts.