Work on artificial gravity. I think that's the top priority. Because right now - the overall health of our astronauts continually decreases month by month - even if they exercise every day. And - is a major challenge to last a year in space and stay healthy - and nobody has yet lasted two years in space.
And in many ways they are not on top form even immediately after hours or days in zero g, body not functioning as well as it does on Earth, appetite less. can't drink as much etc, heart rate faster, red blood cell count way down etc.
Then work on closed biological systems, using algae to generate oxygen for instance (already shown to work in ground experiments by Russia but never flown).
We have to find something better than the present system where you have to supply tons per astronaut to orbit every few months - and dispose of tons of waste as well in the Earth's atmosphere.
Apart from anything else, is hugely expensive. If we didn't have to do that, then for the same budget, could have, perhaps half a dozen different space stations, with 6 astronauts or more in each one - including some at far side of the Moon supplied only every year or two, maybe eventually others orbiting other planets in the solar system once we get over the various inevitable teething problems and technical hitches.
Also - ways of improving cosmic radiation protection. That could be mainly - finding ways to reduce cost of lift to orbit - or else - ways of getting hold of water etc for protection of habitats from NEOs.
But - though there is lots of work on these ideas in theory, and on the ground a bit of work being done - there is no work being done in space.
We need to try these out, at least on a small scale, in space. Otherwise a lot of it is guesswork, especially when human biology enters into it.
E.g., why is it that no-one has ever tried generating oxygen from algae in space? What's the point in doing the ground experiments if they never get applied to space conditions?
And why - after decades of theoretical ground work - has nobody done any artificial gravity experiments in space?
I think - that it's not really a shortage of work on the ground that's the issue right now - but political willingness to try out some of these ideas in space to see if they work. If there was some attempt to do that - I think momentum would grow, you'd get more ground experiments once more also, to try to understand and validate the space results - and to support the astronauts in space.