Matt Wortham

Thanks for the kind words Scott!

Based on these preclinical studies, we consider SIRT2 a promising target for stimulating beta cell regeneration in diabetes. Thank you NIH & Breakthrough T1D for funding, @iidp.bsky.social for islets, and collaborators Orian Shirihai, Kristen Wells, @goniaguy4.bsky.social, & @auwerx-lab.bsky.social!

Mechanistically, SIRT2 deacetylates glycolytic and TCA enzymes, dampening islet oxygen consumption during hyperglycemia. In addition to its direct effect on metabolism, SIRT2 impacts how beta cells transcriptionally interpret hyperglycemia as a stress.

We show that inactivation of SIRT2 increases beta cell proliferation in mice when glucose is elevated above the physiological set point, indicating SIRT2 dampens adaptive beta cell proliferation. SIRT2 also restrains human beta cell proliferation but over a broader range of glucose concentrations.

First off, huge shoutout to co-first authors Bastian Ramms, Chun Zeng, and Jackie Benthuysen from Maike Sander’s lab, and to those who helped with revision experiments including my new colleagues at @cuanschutz.bsky.social @cudevbio.bsky.social

Out today in @jclinical-invest.bsky.social! We discovered a novel regulator of adaptive beta cell proliferation, the protein deacetylase SIRT2, that acts through a metabolic mechanism. Bluetorial below (1/5).
tinyurl.com/ydvv9u2s

With credit to @huisinglab.bsky.social for inspiring the tradition, today we bid farewell to our very first lab member Sean Lee who is joining the Cell Biology, Stem Cells, and Development PhD program here at @cuanschutz.bsky.social‬. Best of luck Sean, we expect great things from you!

VDAC1 is a target for pharmacologically induced insulin hypersecretion in β cells β cells are dysfunctional in type 2 diabetes (T2D) and congenital hyperinsulinism (HI), but the mechanisms linking hypersecretion to β cell failure ar…

These are two important papers that profile beta cell excitotoxicity in response to a sulfonylurea or the VDAC1-stabilizing molecule SW016789. Comparing these studies should make for an excellent journal club. Congrats to all authors! @kalwat.bsky.social tinyurl.com/fwrzrtk9 tinyurl.com/3nzfsp79

Glucose metabolism and regulation in establishing human stem cell-derived β cell maturation Efforts to generate mature stem cell-derived β (SC-β) cells have been ongoing for decades, yet their functional performance still falls short of prima…

Review on metabolism in stem cell derived beta cells from former PhD student with us, Frank Lin. Cell Reports @cp-cellreports.bsky.social

www.sciencedirect.com/science/arti...

How do non-coding variants in enhancers lead to disease? Happy to share our recent work, led by @ewholling.bsky.social, in which we discovered that poised chromatin sensitizes enhancers to aberrant activation by non-coding mutations, contributing to disease. www.biorxiv.org/content/10.1... 1/

Autoreactive T Cells and Cytokine Stress Drive β-Cell Senescence Entry and Accumulation in Type 1 Diabetes Type 1 diabetes (T1D) results from a complex dialogue between the immune system and islets characterized by T cell–mediated autoimmune destruction of pancr

Very excited to share new work on the origins of beta cell senescence in #T1D led by talented PhD student Jasmine Pipella! 🥂🎉 online today!

diabetesjournals.org/diabetes/art...

The U.S. Lit a Beacon for Science. Under Trump, Scientists Fear It’s Dimming

Talked to @KateZernike at @nytimes about my journey and the current moment for scientists in the U.S.

“Ardem Patapoutian’s story is not just the American dream, it is the dream of American science.”

Read the article here. No subscription required:

www.nytimes.com/2025/06/03/u...

Actin remodeling in beta cells adds new layers of upstream regulation - Congrats! @ronnyhelman.bsky.social

Role of GLP1-receptor-mediated α-β-cell communication in functional β-cell heterogeneity. While the islet β-cells were traditionally viewed as a singular functional entity, findings of 1970s and up until recent years, reveal that individual β-cells differ in their calcium dynamics and insu...

Check out this pre-print from Vira Kravets, Andraz Stozer and myself, for the influence of alpha cells on heterogenous islet Ca2+ responses, including first-responders and first phase timing/amplitude. Was great to be part of this!

www.biorxiv.org/content/10.1...

Check out my talk this afternoon where I’ll share our latest work! #isletbiology #metabolism #IMM The University of Texas Health Science Center at Houston (UTHealth Houston)

Our lab website www.worthamlab.org is now live! By the way, we are recruiting at all levels. If our work interests you, consider joining us for cutting edge research in a collegial environment at University of Colorado Anschutz. Not to mention that Denver is a great place to live.

Neonatal fungi promote lifelong metabolic health through macrophage-dependent β cell development Loss of early-life microbial diversity is correlated with diabetes, yet mechanisms by which microbes influence disease remain elusive. We report a critical neonatal window in mice when microbiota disr...

A fungus (Candida dubliniensis) macrophage axis in neonatal mice is required for optimal beta cell development and function throughout the lifespan with the fungus also exerting beta cell regenerative properties in experimental models of #diabetes @science.org www.science.org/doi/10.1126/...

Functional #insulin secretory defects occur in the remaining mass of beta cells during human #T1D pathogenesis not strictly correlated with the extent of insulitis #islets www.biorxiv.org/content/10.1...

Abstracts for #METPHYS2025 are due this Friday!
There are multiple short talks available!

FEB28 is also the deadline for the Vanderbilt Vibrant program

This initiative will provide several awards of $2000 to help new investigators attend

www.sablesys.com/metphys2025-...

We link molecular and functional phenotypes of islet cells from donors with type 1 diabetes to understand impaired insulin and glucagon secretion. Immune signalling, nuclear exclusion, mTOR and lysosomes in alpha cell dysfunction.

https://www.biorxiv.org/content/10.1101/2025.02.20.639325v1

Congrats Aaron! This is such a cool model.

Islet single-cell transcriptomic profiling during obesity-induced beta cell expansion in female mice Targeting beta cell proliferation is an appealing approach to restore glucose control in type 1 diabetes. However, the underlying mechanisms of beta cell proliferation remain incompletely understood, ...

Excited to share our publication in @cp-iscience.bsky.social
Islet single-cell transcriptomic profiling during obesity-induced beta cell expansion in female mice #IMM @uthealthhouston.bsky.social @bcmhouston.bsky.social 🧵 www.cell.com/iscience/ful...

Cutting NIH funds hurts all Americans.

Why? Three main reasons:

#1: These funds support a huge industry in all states. For every $1 of NIH funding generated, there is a short-term return of ~$2.46 in economic activity. $4B in cuts will take away $10B from the economy.

Spatial single-cell isotope tracing reveals heterogeneity of de novo fatty acid synthesis in cancer - Nature Metabolism Buglakova et al. present 13C-SpaceM, a method that combines stable isotope tracing with imaging mass spectrometry thus enabling spatial analysis of lipid dynamics with near-single-cell resolution in t...

Looking forward to discussing this technique for single cell spatially resolved metabolic tracing in BDC journal club today at 10AM MT—don’t miss it!
www.nature.com/articles/s42...

Heterogeneous enhancer states orchestrate β cell responses to metabolic stress - Nature Communications β cell dysfunction contributes to the onset of type 2 diabetes. Here the authors profile single-nuclei RNA along with enhancer marks H3K4me1 or H3K27ac in islets and suggest highly heterogeneous enhan...

Looking forward to journal club tomorrow where we will discuss this fantastic paper from Zong Wei's lab describing how diet-induced obesity impacts enhancer-associated histone modifications in islets www.nature.com/articles/s41...

Cool paper, congrats! Beta cells do not tolerate intermittent fasting (24h every third day) during adolescence, which contrasts with beneficial effects in old mice. Might there be a very high sensitivity of beta cells to altered feeding rhythms during a late stage of functional maturation?

Advances in basic biology and translation in islet research - Nature Reviews Endocrinology Advances in islet cell biology over the past few years highlight a fundamental role for intra-islet endocrine cell interactions and δ-cells in the regulation of glycaemia. New insights into how cellul...

What a pleasant surprise for our recent paper by Dr. Jessica Huang to feature in the 'Year in Review' issue of Nature Reviews Endocrinology - courtesy of Prof. Carmela Evans-Molina. ;-)

doi.org/10.1038/s415...

A comprehensive and much-needed assessment of donor/islet features (and potential confounders) associated with hormone secretion by isolated human islets. Delta cell abundance is anti-correlated with several aspects of beta cell function and seemingly influenced by T2D genetic risk score (!)

The only thing I am missing here is Epigenetic Hulk account.

go.bsky.app/3wdSpdi

It can be difficult to recreate your following list here, please comment/tag any other islet/panc people I am missing and I will edit the pack.