Author | Lightnews

Ani Deshpande Lab @anideshpande.bsky.social · Sep 20

Full Episode here ! youtu.be/TEhPlF29yl4

E5 Diabetes - Sensing Sugar Spikes

YouTube video by Discovery Dialogues

youtu.be

Ani Deshpande Lab @anideshpande.bsky.social · Sep 20

I also experiment with a CGM and share opinions on what these devices can tell us and what they can't. #discoverydialogues #diabetes #cgm #podcast #medicalhistory #Type1Diabetes #type2diabetes

1 1

Ani Deshpande Lab @anideshpande.bsky.social · Sep 20

From a Holocaust survivor to one of the most prolific innovators in recent times, Heller's story is absolutely incredible.

1

Ani Deshpande Lab @anideshpande.bsky.social · Sep 20

A 60 second video clip of Episode 5 in which we chronicle the fascinating story behind Continuous Glucose Monitors (CGMs) and of Adam Heller the man who built technologies that advanced these devices.

1 2

Reposted by Ani Deshpande Lab

Sanford Burnham Prebys @sbpdiscovery.bsky.social · Sep 10

🔬 New research from the @anideshpande.bsky.social Deshpande lab at Sanford Burnham Prebys.
The study demonstrates how public genomic screening data can be used to uncover a new genetic vulnerability in synovial sarcoma.
👏 Shout out to Rema Iyer, PhD lead author of the manuscript.

Sizing up a weakness in synovial sarcoma’s genes

1 1 1

Ani Deshpande Lab @anideshpande.bsky.social · Aug 18

This project was led by a highly talented grad student Rema Iyer with help from others in the lab esp. Anagha Deshpande, and fantastic collaborators at @sbpdiscovery.bsky.social including Ben Finlay, @ Vuori Lab Gerard Brien (Edinburgh), Hiromi Wetterstein (UCSD) and @alice.soragnilab.com @ (UCLA).

Ani Deshpande Lab @anideshpande.bsky.social · Aug 18

Finally, TAK-981 robustly suppressed tumor growth in xenograft models, reducing tumor growth, decreasing SS18::SSX protein levels, and lower cellularity. This study strongly indicates SUMO2 inhibition as an effective therapeutic strategy against synovial sarcoma in vivo.

1 1

Ani Deshpande Lab @anideshpande.bsky.social · Aug 18

Prior studies (McBride et al., Benabdallah N. et al., Boulay G. et al.,) have demonstrated H2AK119ub activation by SS18::SSX fusions. We observed that SUMO2 inhibition substantially reduced H2AK119ub, esp. at fusion target sites corresponding with fusion loss.

1

Ani Deshpande Lab @anideshpande.bsky.social · Aug 18

These results were borne out by CUT&Tag which showed strongly diminished SS18::SSX fusion protein on chromatin after SUMO2 inhibition using TAK-981.

1

Ani Deshpande Lab @anideshpande.bsky.social · Aug 18

Surprisingly, SUMO2 inhibition did not just reverse downstream targets, but also SS18::SSX protein levels themselves. Both shRNA and TAK-981 treatments lowered fusion protein levels across different variants (SSX1 and SSX2), establishing SUMO2 as a regulator of the fusion itself.

1

Ani Deshpande Lab @anideshpande.bsky.social · Aug 18

This was a surprise - reminiscent of candidates that target the fusion protein itself - or immediately proximal targets. Excited by this, we tested whether SUMO2 inhibition targets the fusion protein.

1

Ani Deshpande Lab @anideshpande.bsky.social · Aug 18

Fusion activated oncogenic targets (e.g., HOXA10, SUZ12, TYMS) were down-regulated, while fusion-repressed genes such (e.g., KLF4, GADD45B) were derepressed upon SUMO2 inhibition.

1

Ani Deshpande Lab @anideshpande.bsky.social · Aug 18

Surprisingly, transcriptomic studies revealed that SUMO2 inhibition showed a dramatic reversal of the transcriptional program of SS18::SSX fusions described in Jerby-Arnon L, et al. (Regev Lab).

1

Ani Deshpande Lab @anideshpande.bsky.social · Aug 18

Genetic knockdown of SUMO2 had similar effects

1

Ani Deshpande Lab @anideshpande.bsky.social · Aug 18

We were also excited about SUMO2 because of the availability of TAK-981, a potent, clinical-stage SUMO2 inhibitor which strongly suppressed growth of synovial sarcoma lines, increased apoptosis, and dramatically reduced colony-forming ability of synovial sarcoma cells at low nM

1 1

Ani Deshpande Lab @anideshpande.bsky.social · Aug 18

We then conducted targeted CRISPR screens in vitro and in vivo using synovial sarcoma cells, and SUMO2 emerged as one of the strongest dependencies in both - validating DepMap predictions. Since SUMO2 was also a SS18::SSX fusion target, was prioritized for further studies.

1

Ani Deshpande Lab @anideshpande.bsky.social · Aug 18

So, we began with the dependency maps dataset (DepMap) to ask: which genes are selectively essential for synovial sarcoma compared to other cancers?

In addition to expected genes (SS18, SSX, BRD9), one pathway jumped out: SUMOylation. And right at the core of this was SUMO2.

1

Ani Deshpande Lab @anideshpande.bsky.social · Aug 18

A few years ago, we got interested in Synovial Sarcoma - an aggressive, difficult-to-treat cancer. There is a single fusion protein - the SS18::SSX fusion - that drives this malignancy, but there isn’t much known about actionable vulnerabilities in this disease.

1

Ani Deshpande Lab @anideshpande.bsky.social · Aug 18

Really excited that our manuscript on Synovial Sarcoma is now online. Link to Open Access PDF: tinyurl.com/55bnssws

A summary🧵 :

1 2 4

Ani Deshpande Lab @anideshpande.bsky.social · Aug 11

In this Episode, Pamela Itkin-Ansari and I explore a chemical reaction that links golden toast and roasted potatoes to chronic disease, and uncover the astonishing story of a breakthrough medical test born in a place no one saw coming. #diabetes #A1C #HbA1c #hemoglobin #glycation #MaillardReaction

1

Ani Deshpande Lab @anideshpande.bsky.social · Aug 11

Sugar is the fuel of life, but we are drowning in it in the modern world. Where does all that excess sugar go, and what quiet damage might it be causing inside us?

E4 Diabetes - A Secret in Your Blood

YouTube video by Discovery Dialogues

www.youtube.com

1 1 4

Ani Deshpande Lab @anideshpande.bsky.social · Jul 2

I’m excited to share that as of July 1, I’ve been promoted to Full Professor. I am immensely grateful for the support of my trainees, mentors, letter writers and colleagues who supported me in reaching this milestone and for those who made this journey meaningful and worthwhile.

3

Ani Deshpande Lab @anideshpande.bsky.social · Jul 2

Awesome Jordan...when you get a chance listen to this one ;-)

podcasts.apple.com/us/podcast/t...

The Discovery Dialogues Podcast

Life Sciences Podcast · Welcome to the Discovery Dialogues podcast, where we take a deep dive into the history of groundbreaking discoveries in the life sciences. I am your host Ani Deshpande. Each e...

podcasts.apple.com

1

Reposted by Ani Deshpande Lab

euanashley @euanashley.bsky.social · Jun 14

Atul Butte died yesterday.
The world lost a giant.
A big bear of a man.
With a huge smile.
With love for everyone.
With energy that could power a room.
I loved everything about Atul.
I loved how he was always happy.
I loved how excited he was about science and helping people.

14 57 190

Ani Deshpande Lab @anideshpande.bsky.social · Jun 7

Always a bittersweet moment when a PhD student from the lab graduates.Terrific work and what a thesis defense talk Rema Iyer ! Congratulations on your degree!

1