MoldoveanuLab

Structural basis of BAK sequestration by MCL-1 in apoptosis dlvr.it/TKFJFw

We also profiled some of the drugs that inhibit MCL-1, but failed thus far in clinical trials due to (cardio)toxicity, and we think there is room for improving them. We thank many wonderful colleagues who collaborated to make this possible. Happy Easter for those who celebrate!

The paper has a bit of something for everyone who enjoys structure, function, & cancer targeting. For instance, we presented a cryo-EM structure of the 40 kDa MCL-1:BAK complex revealing features we think apply to the relevant BCL-2 family interactome.

Apoptosis inhibition: MCL-1 vs BAK Our new study published in Molecular Cell featuring classic BCL-2 family proteins inhibition of apoptosis by oncogene MCL-1 who blocks mitochondrial outer membrane permeabilization by the pore-forming protein BAK: authors.elsevier.com/a/1ktSg3vVUPVZ…

We are hiring! Please see these two opportunities to become part of our National Resource Team. Principal Staff Scientist uasys.wd5.myworkdayjobs.com/en-US/UAMS_All… Associate Staff Scientist uasys.wd5.myworkdayjobs.com/en-US/UAMS_All…

BTW, our new lab @UAMS_Biochem @uamscancer is now seeking scientists interested in addressing open questions in cell death research and cancer biology with structural (cryo-EM🤍) and chemical biology tools! DM me if curious. We make science fun!

Are all folded BCL-2 family proteins pore-forming? It surely seems that if one tries hard enough they could be made pore-formers, but now clearly 4 of them stand out: BAK, BAX, BOK & tBID. I reflect on this problem in #BioEssays onlinelibrary.wiley.com/doi/full/10.10…

Our latest work on chromatin and ribosomes was published today. Great collaboration with @kriwacki lab. Congratulations to everyone involved. authors.elsevier.com/sd/article/S10…

@CellDeathLab This is an excellent resource to reshape our understanding of toxicity in targeting cancer. Congrats y’all! ADCs…

📰Our analysis of apoptosis regulation in vascular endothelial and smooth muscle cells is now published! We find that cells comprising the vasculature are primed to die, rendering them hypersensitive to anti-cancer agents to drive cardiovascular tox! 🧵1/n science.org/doi/10.1126/sc…

@JoanMonte @UniBarcelona @CampusClinicUB @CellComBcn @DrTonyLetai @samitierjosep So happy for you Joan! Well deserved and hope you are enjoying and celebrating. Congrats

Delighted to share that I have been promoted to Associate Professor (tenured) at @UniBarcelona @CampusClinicUB @CellComBcn. This would not have been possible without the support of my family, friends, colleagues and mentors @DrTonyLetai @samitierjosep and Prof. Agell. Thank you!

RNA splicing defects contribute to Alzheimer’s disease - St. Jude. Grateful for the contribution of all group members and collaborators, Drs. Yu, Beach, Bennett, Wu, Chen, ⁦Zakharenko, ⁦@mikedyerlab⁩, ⁦@RSmeyne⁩, ⁦@MoldoveanuLab⁩ stjude.org/media-resource…

@CellDeathLab @ShaynaSarosiek @camfraser13 @BU_Amyloidosis @vsanchorawala Congratulations for an outstanding, thorough effort demonstrating the mechanistic dependency and feasibility of targeting mitochondrial apoptosis directly (with BH3 mimetics) in AL amyloidosis. Very cool!

Co-senior author @ShaynaSarosiek and I are incredibly grateful to the patients for participating and to 1st author @camfraser13 for YEARS of hard work. We also want to thank the team at @BU_Amyloidosis and especially @vsanchorawala for their pivotal expertise and support. (/end)

We're excited to share our report on apoptotic vulnerabilities in AL amyloidosis. We analyzed over 50 primary specimens from AL patients at @BU_Amyloidosis and find that clonal plasma cells are frequently dependent on BCL-2 or MCL-1 for survival. (1/n) nature.com/articles/s4146…

@MoldoveanuLab @iScience_CP @GeetikaGitika2 We are honored to have contributed to this exciting discovery of the novel BAK activator SJ572946. We believe direct modulation of #apoptosis can help treat or prevent a wide range of diseases, including cancers, and this discovery helps bring us closer to that goal.

@MoldoveanuLab @CristinaGuibao @RichardLeeLab @zintisinde Congratulations @MoldoveanuLab and collaborators on this important advance. We regret that Geetika wasn't able to celebrate with you but know that this paper can serve as part of her scientific legacy.

@MoldoveanuLab @iScience_CP @GeetikaGitika2 Geetika was such a bright spark. The dedication is a great way to remember her.

Special thanks to our outstanding lab members and collaborators at St. Jude and Harvard including @CristinaGuibao, @RichardLeeLab, Kris Sarosiek and his crew @CellDeathLab including @zintisinde, and all twitter-less others. RIP Geetika

The most useful use, however, has been to probe the mechanism of BAK activation and we show that our lead compound cooperates with BID to activate a BAK mutant severely impaired in apoptosis initiation

We dedicate @iScience_CP paper on #apoptosis initiation with BAK activators to Dr. Geetika Singh @GeetikaGitika2, who recently lost her life to cancer. We are humbled by this tragedy and grateful for life and important contributions at many levels. doi:10.1016/j.isci.2022.105064