(1/13) Please RT: our first #tweetorial!
Here's a
on our new paper which is also my 1st time being (joint) last author
Congrats to all, especially superstar med student @LuszczakSabina!
#AcademicTwitter @AcademicChatter @OpenAcademics #womeninSTEM https://www.nature.com/articles/s41598-020-71263-9
Here's a


Congrats to all, especially superstar med student @LuszczakSabina!
#AcademicTwitter @AcademicChatter @OpenAcademics #womeninSTEM https://www.nature.com/articles/s41598-020-71263-9
(2/13) In #prostatecancer cell lines & human tissue, co-targeting #PIM & #PI3K #kinases seems promising!
We reckon ~20% of prostate cancer patients could benefit from this approach in future & these tend to be the sicker patients.
Scroll for #science! https://www.nature.com/articles/s41598-020-71263-9
We reckon ~20% of prostate cancer patients could benefit from this approach in future & these tend to be the sicker patients.
Scroll for #science! https://www.nature.com/articles/s41598-020-71263-9
(3/13) Fig1a:
From publicly available data we see that some patients overexpress either the #PIM pathway, the #PI3K pathway, or both. Each of these targets have inhibitors in development, that could theoretically be of benefit to any of these patient groups when combined
From publicly available data we see that some patients overexpress either the #PIM pathway, the #PI3K pathway, or both. Each of these targets have inhibitors in development, that could theoretically be of benefit to any of these patient groups when combined

(4/13) Fig1b+c:
These patients who could hopefully benefit from this co-targeted approach also happen to tend to be sicker (higher Gleason, lower survival)
These patients who could hopefully benefit from this co-targeted approach also happen to tend to be sicker (higher Gleason, lower survival)

(5/13) Fig2:
At the RNA level in 3 #prostatecancer cell lines, inhibition of #PIM/ #PI3K lead to decreased expression of a range of downstream genes, & co-targeted inhibition of both pathways lead to decreased expression of a wider range of #genes, as you might expect!
At the RNA level in 3 #prostatecancer cell lines, inhibition of #PIM/ #PI3K lead to decreased expression of a range of downstream genes, & co-targeted inhibition of both pathways lead to decreased expression of a wider range of #genes, as you might expect!
(6/13) Fig3: At the phospho-protein level, we see similar trends, with the co-targeted approach yielding the most striking inhibition, particularly in the most aggressive cell line (C4-2B) - this was encouraging

(7/13) Fig4: All the inhibitors lead to dose-dependent reductions in proliferation in all cell lines, with the lowest IC50s coming from the triple kinase inhibitor #AUM302, in the nM range.
Nice drug! Thanks: @AumBiosciences @InflectionBio @CNIOStopCancer #drugdevelopment
Nice drug! Thanks: @AumBiosciences @InflectionBio @CNIOStopCancer #drugdevelopment
(8/13) Fig5: In human #exvivo cultures, we see the same story, with improved inhibition of proliferation & induction of apoptosis when we co-target both pathways. Note the conc differences!
This fig is a taster of the work to be expanded on in my new lab #comingsoon #heaveylab
This fig is a taster of the work to be expanded on in my new lab #comingsoon #heaveylab
(9/13) limitations: the ex vivo work is only in a few patients, we may have been lucky & we can’t assume this would work so well for everyone – probably only around a fifth will respond like this. Or maybe more… only one way to find out!
(10/13) Next steps: @ProstateUK @MovemberUK have funded us to expand this cohort substantially & carry out detailed molecular work. Much of the collection & culture has already happened, with thanks to @UCLpathology @uclhrobotics
https://prostatecanceruk.org/research/research-we-fund/tld-pf16-004 #fellowship #womeninSTEM
https://prostatecanceruk.org/research/research-we-fund/tld-pf16-004 #fellowship #womeninSTEM
(11/13) Acknowledgements [part 1] for the work above!
Big thanks to the authors including these tweeters -follow them! @LuszczakSabina @HayleyWhitaker @kathygately1 @b3nsimp @hayleyjeanpye @linamacarmona @aimhaider @acesridhar @greglshaw @TheWhitakerlab https://www.nature.com/articles/s41598-020-71263-9
Big thanks to the authors including these tweeters -follow them! @LuszczakSabina @HayleyWhitaker @kathygately1 @b3nsimp @hayleyjeanpye @linamacarmona @aimhaider @acesridhar @greglshaw @TheWhitakerlab https://www.nature.com/articles/s41598-020-71263-9
(12/13) Acknowledgements [part 2] for the work above!
Many thanks for supporting this work:
Collab: @InflectionBio @AumBiosciences
Journal: @SciReports @SpringerNature
Funders: @ProstateUK @MovemberUK
Hosts: @UCLDivofSurgery @UCL @UCLpathology @uclhrobotics https://www.nature.com/articles/s41598-020-71263-9
Many thanks for supporting this work:
Collab: @InflectionBio @AumBiosciences
Journal: @SciReports @SpringerNature
Funders: @ProstateUK @MovemberUK
Hosts: @UCLDivofSurgery @UCL @UCLpathology @uclhrobotics https://www.nature.com/articles/s41598-020-71263-9
(13/13) Now we party? 



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please imagine them 2m apart
)
#publication #AcademicChatter #AcademicTwitter #WomeninSTEM #scicomm
https://www.nature.com/articles/s41598-020-71263-9




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#publication #AcademicChatter #AcademicTwitter #WomeninSTEM #scicomm
https://www.nature.com/articles/s41598-020-71263-9