John’s New York stage appearances included Broadway’s Big River, The Secret Garden, Six Degrees of Separation, and Larry Kramer’s The Destiny of Me for which he won an Obie Award. He starred in and wrote the book for the original 1998 Off-Broadway production of Hedwig and the Angry Inch for which he won an Obie Award along with co-creator composer Stephen Trask. In 2001 John directed, wrote, and starred in the film adaptation which won him Best Director at Sundance and a Golden Globe nomination for Best Actor. He was executive producer of Jonathan Caouette's documentary Tarnation (2004) and his sexually frank improv-based film Shortbus was released in 2006. He directed Rabbit Hole (2011) adapted from the Pulitzer Prize-winning play and starring Nicole Kidman in an Oscar-nominated performance.
He’s also appearing as a recurring character on the HBO series “Girls” and preparing to direct a film adaptation of Neil Gaiman’s punk era story How to Talk to Girls at Parties.