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Matt Wortham

@worthamlab.bsky.social

130 followers 98 following 17 posts

Assistant Professor at the Barbara Davis Center for Diabetes at University of Colorado Anschutz. The Wortham lab studies how nutrients govern adaptive and maladaptive responses by pancreatic beta cells in health and metabolic disease. www.worthamlab.org

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Matt Wortham @worthamlab.bsky.social · 6d

It's great to see the final version of our SIRT2 paper in JCI along with an astute commentary from trailblazers in beta cell regeneration—thanks for highlighting our work! @likatz.bsky.social @donaldscottmssm.bsky.social @jci.org @sanderlaberlin.bsky.social tinyurl.com/y6rx69x7 tinyurl.com/ydvv9u2s

Reposted by Matt Wortham

Mollie Huber @molliehuber.bsky.social · Aug 28

I am excited to announce our paper “Beta cell dysfunction occurs independently of insulitis in type 1 diabetes pathogenesis” is out in Cell Reports! @eaphelps.bsky.social
www.cell.com/cell-reports...

Beta cell dysfunction occurs independently of insulitis in type 1 diabetes pathogenesis

Huber et al. used live pancreas slices from donors with recently diagnosed type 1 diabetes to reveal beta cell dysfunction independent of local immune cells. Real-time imaging and molecular analyses u...

Reposted by Matt Wortham

Dr. Jeffrey Millman @jeffreymillman.bsky.social · Aug 25

Join us for the 2025 Rachmiel Levine-Arthur Riggs Diabetes Research Symposium. We have an amazing program this year focusing on type 1 #diabetes. We have also extended the abstract submission deadline to Sept 19. Register and submit your abstract a www.levinesymposium.com

Reposted by Matt Wortham

Vincent Poitout 🇨🇦 @vpoitout.bsky.social · Aug 18

It was great fun to write this review with friends and colleagues Melkam Kebede, Belinda Yau, @jinghughes.bsky.social and Julien Ghislain

Diabetologia @diabetologiajnl.bsky.social · Aug 18

New review highlights recent progress in our understanding of the role of the beta cell in type 2 diabetes. #diabetes #islet @jinghughes.bsky.social @vpoitout.bsky.social link.springer.com/article/10.1... 🔓

The role of the beta cell in type 2 diabetes: new findings from the last 5 years - Diabetologia

Recent advances in genome-wide approaches, the availability of isolated human islets for research and the evaluation of novel incretin mimetics in large clinical trials have brought about remarkable p...

link.springer.com

Matt Wortham @worthamlab.bsky.social · Aug 15

Simultaneous in vivo calcium imaging of up to 100 islets coupled with CGM measurements in lean and ob/ob mice—this is impressive! www.biorxiv.org/content/10.1...

Glycemia Shift Pancreatic Islets Rhythmicity via δ-α Cell in vivo, Impairment in Diabetes

Blood glucose homeostasis relies on the well-coordinated rhythmic activity of millions of islets throughout the pancreas. Islet rhythmicity is triggered by glucose elevation and mediated by paracrine ...

www.biorxiv.org

Matt Wortham @worthamlab.bsky.social · Jul 31

Thanks for the kind words Scott!

Matt Wortham @worthamlab.bsky.social · Jul 31

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!

Matt Wortham @worthamlab.bsky.social · Jul 31

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.

Matt Wortham @worthamlab.bsky.social · Jul 31

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.

Matt Wortham @worthamlab.bsky.social · Jul 31

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

Matt Wortham @worthamlab.bsky.social · Jul 31

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

JCI - The protein deacetylase SIRT2 exerts metabolic control over adaptive β cell proliferation

Matt Wortham @worthamlab.bsky.social · Jun 30

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!

Matt Wortham @worthamlab.bsky.social · Jun 30

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

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…

www.sciencedirect.com

Reposted by Matt Wortham

Patrick MacDonald🇨🇦 @bcellorg.bsky.social · Jun 25

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...

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…

www.sciencedirect.com

Reposted by Matt Wortham

Evgeny Kvon @evgenykvon.bsky.social · Jun 23

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/

Reposted by Matt Wortham

Peter Thompson @thompsonisletlab.bsky.social · Jun 11

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...

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

diabetesjournals.org

Reposted by Matt Wortham

Ardem Patapoutian @ardemp.bskyverified.social · Jun 3

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...

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

www.nytimes.com

Reposted by Matt Wortham

Mike Kalwat @kalwat.bsky.social · May 19

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

Ronny Helman @ronnyhelman.bsky.social · May 18

Happy to share a work from the Helman lab on how beta cells sense and control their insulin secretion by Krell et al. in @CellReports.

Beta cells intrinsically sense and limit their secretory activity via mTORC1-RhoA signaling: Cell Reports www.cell.com/cell-reports...

Beta cells intrinsically sense and limit their secretory activity via mTORC1-RhoA signaling

Krell et al. show that mTORC1 in β cells acts as an activity sensor, activated by the same signals that trigger insulin secretion. This activation, in turn, inhibits insulin release via RhoA-dependent...

Reposted by Matt Wortham

Richard Benninger @bennyscience.bsky.social · Apr 29

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...

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...

www.biorxiv.org

Reposted by Matt Wortham

Aaron Cox, PhD @aaronrcox.bsky.social · Apr 3

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)

Matt Wortham @worthamlab.bsky.social · Mar 25

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.

www.worthamlab.org

Reposted by Matt Wortham

Daniel Drucker @danieljdrucker.bsky.social · Mar 6

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/...

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...

www.science.org

Reposted by Matt Wortham

Daniel Drucker @danieljdrucker.bsky.social · Feb 25

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...

Reposted by Matt Wortham

Phillip White @phillipjwhitephd.bsky.social · Feb 24

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-...

Reposted by Matt Wortham

Patrick MacDonald🇨🇦 @bcellorg.bsky.social · Feb 21

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