Shiv K Singh & Lab
@ShivKSingh6
Followers
680
Following
3K
Media
47
Statuses
513
Our research focuses on the spatial heterogeneity and plasticity of tumor cells within the immune microenvironment of pancreatic tumors @yourUMG @uniGoettigen
Göttingen, Germany
Joined December 2018
📢 Happy to share our new study in @ScienceAdvances 🔥. 🚨 We explore why pancreatic cancer cells survive after eliminating oncogenic missense TP53 (misp53) mutants, and how they continue to grow despite clinical therapies💊. 🧵1/11.👉
4
11
34
RT @NelsonDusetti: Proud to have contributed to this new work in Science Advances! Congrats to @ShivKSingh6 and team for revealing how TP5….
science.org
Misp53 mutant specificity affects tumor plasticity and therapy response in PDAC.
0
4
0
🧵11/ Huge thank you to @dfg_public, @kfo_5002, and @Krebshilfe_Bonn, with significant support from @SanderStiftung and the Fritz-Thyssen Stiftung!!.
1
0
3
🧵10/ We also greatly appreciate our collaborators and especially to @NelsonDusetti for his timely support and contributions!.
2
0
3
. and our fantastic lab team for their strong support throughout this journey. Special thanks to @frederikepenz, @rebeccadiya, and @LukasKlein01 !.
1
0
2
🧵9/👏 huge shoutout to @UrbachLaura for her incredible work on this study, —what an incredible accomplishment after four years of her PhD journey! A big thank you to Lena Wieland for her fantastic support with her master’s thesis and during the revision process. .
1
0
2
🧵8/ thus, using a combination of Palbociclib + Trametinib(MAPK/ERK inhibitor), not only counteracts Palbociclib adaptation but also effectively overcomes misp53R273H/C-driven plasticity.
1
0
2
🧵7/ 🔬Our combined multiplex IF/IHC imaging revealed the spatial distribution and mutual exclusivity patterns of p-ERK and misp53R273H hotspot regions in neoplastic cells within misp53 knockdown orthotopic tumors
1
0
2
🧵6/ We suggest that a compensatory mechanism has emerged: These observations indicate that Palbo, or p53 loss, leads to increased p-ERK and a reduction in misp53 levels, suggesting that the MAPK/ERK pathway compensates to promote cell cycle progression in the absence of misp53
1
0
2
🧵5/ Our findings show that misp53 is linked to cell cycle plasticity. 💡we were surprised to find that CDK4/6 cell cycle inhibitor 'Palbociclib' reduces misp53R273H levels. However, in PDAC cells treated with Palbociclib did not effectively slow down cell growth.
1
0
2
🧬2️⃣it blocks E2F4-mediated cell cycle repression function together with DREAM family proteins, allow cell cycle progression and induction of cell cycle genes! Loss of misp53R273H/C facilitated E2F4 binding to the promoters of E2F1, RBL1, and PCNA
1
0
2
🧵4/ 🧬What is the mechanism of misp53-mediated cell cycle regulation and plasticity? Misp53R273H/C fuels the cell cycle in two ways: .🧬1️⃣it sequesters active Rb (pRb) from E2F1 promoters, facilitating cell cycle progression and promoting PDAC growth
1
0
2
🧵3/ Loss of misp53R273H reduced tumor burden, liver metastases & improved survival in orthotopic PDAC models
1
0
2
🧵2/ We found that misp53R273H/C, unlike misp53R248W/Q, drives enhanced cell cycle plasticity by transcriptionally regulating the E2F/G2M pathways, resulting in aggressive PDAC growth
1
0
2
🧵1/ We investigate how two misp53 mutants (misp53R273H/C vs. misp53R248W/Q) affect tumor plasticity and therapeutic vulnerabilities in PDAC
1
0
2
RT @dana_peer: I am thrilled to share with the world a new preprint, spearheaded by the truly amazing Jose Reyes in partnership with @Lowe….
biorxiv.org
The transition from benign to malignant growth is a pivotal yet poorly understood step in cancer progression that marks the shift from a pathologically inert condition to a clinically lethal disease....
0
39
0
RT @Aiims1742: Congratulations to @IamLinghua @GuangshengPei @jiminmin_v and all our exceptional collaborators at @MDAndersonNews & beyond….
0
18
0
RT @AkisPapantonis: Hear, hear! .@yourUMG is inviting applications to its new Medical Scientist Program “Genomic responses to disease plast….
0
5
0
RT @ElisaEspinet: Another amazing piece of work from @ShivKSingh6 lab with @BarbaraGrnwald 😃 As always, crazy amount of data and provocativ….
0
4
0
RT @BarbaraGrnwald: 🚨New paper alert: Intratumoral co-existence of PDAC subtypes -- what's the environmental drivers and underlying mechani….
0
7
0