Oscar-winning filmmaker Jonathan Demme, best-known for directing the 1991 horror classic The Silence of the Lambs, has passed away. His publicist confirmed the sad news: Demme died in New York on Wednesday due to complications with cancer. Demme was 73-years old.

With over 62 directorial credits to his name, Demme holds one of the most distinctive and eclectic filmographies in modern Hollywood history. While best known for helming The Silence of the Lambs  – and thus introducing moviegoers to the charmingly frightening Hannibal Lector (Anthony Hopkins) and plucky FBI upstart Clarice Starling (Jodie Foster) – Demme held a wide-ranging body of work that consisted of quirky, humanistic character studies (Rachel Getting Married), prestige dramas (Philadelphia), thrillers (The Manchurian Candidate). He also directed several documentaries, several musical-themed (Neil Young: Heart of Gold) and others more socio-politically bent (Jimmy Carter: Man From Plains).

Demme broke out as a student of heralded B-movie producer Roger Corman, and made his directorial debut with Corman’s Angels Hard as They Come (1971), a biker film. He started to make a name for himself in the mid-to-late 1970s with a diverse stew of films that included Crazy Mama (1975), Fighting Mad (1976) and Handle with Care (1977) before breaking out further with the well-received 1980 comedy Melvin and Howard. That film, which starred Paul Le Mat, Jason Robards and Mary Steenburgen, centered on a hard-on-his-luck guy who finds the beneficiary of Howard Hughes’ will, a claim of dubious authenticity. The quirky high-concept premise paid off, even winning two Oscars: for Best Supporting Actress (Steenburgen) and Bo Goldman’s original screenplay.

The 1980s saw greater success for Demme with a diverse slate of critically admired films that included Swing Shift (1984), Something Wild (1986) and Married to the Mob (1988), yet the biggest success of his career would come with The Silence of the Lambs. The horror entry, based on the novel by Thomas Harris, became an unlikely box office champion and proved further iconic thanks to the performances of Hopkins and Foster, both of whom won Academy Awards for their portrayals. The film took home three more Academy Awards, for Ted Tally’s screenplay, Demme’s direction as well as Best Picture; the film also became only the third movie in Oscar history to win “The Big 5” – Picture, Director, Actor, Actress and Screenplay (It Happened One Night and One Flew Over the Cuckoo’s Nest being the other two).

Building on the momentum of The Silence of the Lambs, Demme followed that feature up with one of his most socially conscious, Philadelphia (1993), one of the very first Hollywood studio pictures to tackle the AIDS crises. Tom Hanks ended up picking up his first Academy Award for his about-faced starring turn. In 1998, Demme directed Beloved, an adaptation of Toni Morrison’s unflinching novel, which starred Oprah Winfrey; the film failed to fully register with audiences or critics. Demme made a mini-comeback with his all-star 2004 remake of The Manchurian Candidate (starring Denzel Washington and Meryl Streep) and the well-received 2008 family dramedy Rachel Getting Married, a film which earned leading lady Anne Hathaway an Oscar nomination. His last feature was the 2015 dramedy Ricki and the Flesh starring Meryl Streep. In between feature films, Demme rounded out a fully body of work with numerous documentary features and stint in television – his last credit was helming a forthcoming episode of the FOX drama Shots Fired.

Demme is survived by second wife Joanne Howard and their three children: Ramona, Brooklyn and Jos.