Gnana Krishnamoorthy

I am a scientist working to understand thyroid cancer pathogenesis with a goal towards developing mechanism-based targeted therapies.

[Vera Tiedje @VeraTiedje]

@jclinicalinvest 9/10 #9:
So many open questions and much more to come...
Shall we pay more attention to CD4 T-cell checkpoints to boost MAPK inhibitor treatment responses?
Could these strategies be leveraged to improve outcomes in ATC patients?

[Vera Tiedje @VeraTiedje]

@jclinicalinvest 8/10 Alright, but how does the loss of an MHC-II dependent mechanism can lead to MAPK resistance?
Depletion of CD4 T-cells, but not CD8 T-cells is controlling the response to MAPK inhibitors!

[Vera Tiedje @VeraTiedje]

@jclinicalinvest 7/10 And.. It is reversible with EZH2 inhibitors.
But does this matter?
It turns out yes. If you ko Ciita or H2-ab1 (MHC II allele) in MAPK-inhibitor sensitive tumors, they become treatment resistant.

[Vera Tiedje @VeraTiedje]

@jclinicalinvest 6/10 But how are tumor cells doing this?
Well, it turns out that ATC’s epigenetic plasticity seems to be behind this. They are silencing the Ciita locus, the master regulator of MHC II!

[Vera Tiedje @VeraTiedje]

@jclinicalinvest 2/10 Using murine models of BRAF/p53-/--mutant ATC, we noted upon treatment with BRAF and MEK inhibitors, significant upregulation of the antigen presentation pathway in tumor cells.

[Vera Tiedje @VeraTiedje]

Now out in @jclinicalinvest ! MHCII expression by tumor cells is critical for response to targeted therapy!!
Tweetorial incoming 👇

[Journal of Clinical Investigation @jclinicalinvest]

Little progress has been made in the treatment of anaplastic thyroid cancer

@VeraTiedje @Gnana_Krish et al. @MSKCancerCenter now find mice with aggressive ATC respond to the inhibitor combination dabrafenib/trametinib by affecting cancer cell MHCII expression & increasing T-cell infiltration.

https://t.co/XXvBBrtaL7

The image shows multiplex immunofluorescence for immune cell populations in the tumor microenvironment of thyroid cancers.

[Journal of Experimental Medicine @JExpMed]

RBM10 loss promotes #metastases by aberrant splicing of cytoskeletal and extracellular matrix mRNAs, say Gnana Krishnamoorthy (@Gnana_Krish), James Fagin and colleagues @MSKCancerCenter: https://t.co/YGQwpF7ekk
@VeraTiedje
#SolidTumors #HumanDiseaseGenetics

[Anthony Glover @DrAntG]

@JExpMed @Gnana_Krish @MSKCancerCenter @VeraTiedje Thanks @JExpMed for highlighting this project which I was able to be part of thanks to @RACSurgeons @tourdecure_aus & @nhmrc to understand why some thyroid cancers are more likely to spread

[Waggoner Lab @LabWaggoner]

RBM10 loss promotes metastases by aberrant splicing of cytoskeletal and extracellular matrix mRNAs @JExpMed @Gnana_Krish
https://t.co/w1chMZfht1

[Gnana Krishnamoorthy @Gnana_Krish]

Out now! Our study reveals the role of RBM10 mutations in driving thyroid cancer metastasis.

Thanks to @MSKCancerCenter, Fagin Lab, @AbdelWahablab @bradleybio @DrAntG @VeraTiedje @AdrianAcunaRuiz @MSaqcena Brian Untch, Jeff Knauf.

[Journal of Experimental Medicine @JExpMed]

Insights: Coughlin and @LedongW @stonybrooku discuss new work by @Gnana_Krish et al. (https://t.co/dTJfpYdvxe) which identifies the loss of the splicing factor RBM10 as a driver of #metastasis in #ThyroidCancer through the regulation of RNA splicing https://t.co/PamiS3oxqV