Answer:
I would take the L to the end of the line in Manhattan, 8th Avenue-14th Street. Then, if you're going to Upper Manhattan or the Bronx, transfer to the Uptown A express train to 59th Street-Columbus Circle, 125th Street or 145th Street, and transfer there to the Uptown D.
If you're going to Lower Manhattan or Brooklyn, transfer to the Downtown A-C-E, 1 stop, to West 4th Street, and transfer there to the Downtown D.