Diamond Lab at UT Southwestern

(1/6) @meladenosine and I are thrilled to announce that the Sanders Lab will launch in November 2023 at UT Southwestern (primary, @UtsWcand; secondary, @UTSWMolBiol and @UTSWBrain). We will pursue curiosity-driven science related to RNA-protein assemblies and diseases of aging!

An elegant McKnight lab paper: bit.ly/3O3AF4o. Pauling H-bonds and aa sequence govern cross-beta-mediated phase separation and tau fibril formation. Beautiful, definitive, biologically plausible.

I’m immensely proud and happy to share our first paper, an outstanding team effort of a junior lab, in the middle of a pandemic, and starting with limited #cryoEM expertise. A thread. biorxiv.org/content/10.110…

A story emerges: tau seeds dock via HSPGs, and directly translocate into the cytoplasm, either at the membrane or from the inside of an endosome. Factors that slow endolysosomal trafficking will increase tau entry into the cytoplasm, as observed also in pubmed.ncbi.nlm.nih.gov/35508140/

Meanwhile, tau assemblies penetrate the plasma membrane (and/or vesicle membrane) like the TAT peptide, requiring HSPGs, recapitulated in vitro using giant plasma membrane vesicles (biorxiv.org/content/10.110…)

Cell basis of tau seeding explored... Seeds traffic to the endolysosome and cytoplasm (where seeding happens), with NO EVIDENCE that tau is toxic to endosomes (pubmed.ncbi.nlm.nih.gov/35525272/).

Two terrific students graduated from the #MDiamond_Lab: Michael LaCroix, Ph.D. (now in med school), and Amy Zwierzchowski-Zarate, Ph.D. Michael found tau seeding in healthy brain (biorxiv.org/content/10.110…); Amy discovered RNA induces specific tau strains (pubmed.ncbi.nlm.nih.gov/35700826/)

Two #tauprotein publications out after a lot of work. RNA specifically induces tau strains pubmed.ncbi.nlm.nih.gov/35700826/, and seeds traffic two ways into the cell, but only one leads to amplification pubmed.ncbi.nlm.nih.gov/35525272/.

Back from Keystone: #Neurinflammation and #Neurodegeneration Conference. Lucky see amazing lab alumna Siling Du, currently in the @jonykipnis lab at Washington University.

What if #tau #prions are not purely pathological, and instead serve a physiologic function? New work by #UTSW #MSTP Michael LaCroix with a conformational #tauantibody finds seeds in healthy control brain! bit.ly/3orbpeg

Congrats to Anthony Vega, Charles White, Satwik Rajaram, Rati Chekheidze, working with #CAND to bring AI to sort out #tauoapathies in a new paper: bit.ly/3vJC3BG. We hope to use knowledge of #tau #strain composition and AI to create tools to improve neuropathology.

Congrats to Sarah Kaufman, Sarah Svirsky, Jon Cherry, and Ann McKee for a groundbreaking new study of CTE pathology (shorturl.at/xGU47). Despite a lot of cortical p-tau, seeding predominates in limbic structures, which may explain unique clinical features of CTE.

Loved the #FASEB meeting on #amyloid last week. So interesting to think about functional vs. non-functional amyloid, and how disease results from too much of one kind. Will we find evidence that #tau actually is EVOLVED to form fibrils and propagate like a #prion?

@GraceHallinan Thanks. This is fascinating. Do you make anything of slight differences in undefined densities around the core of the fibrils vs. AD structures? We are very interested in this work!

Excited and proud to share our new paper, which was published yesterday in Acta Neuropathologica! Using cryoEM, we determined for the first time the atomic structure of Tau protein from two genetic Prion diseases link.springer.com/article/10.100…

Corollary: Imagine a weight loss drug that caused an average of 1 pound loss in a population of 1000 people. Statistically but not clinically significant! Similar effects for #aduhelm. Beware of statistics in science.

Thanks @priyanka_runwal and @natgeo for a thoughtful article on the issues surrounding #aduhelm. Appreciate being consulted! #amyloid #alzheimers #FDA #tau #neurodegeneration on.natgeo.com/3pM3S9m

We are #hiring! Looking for an experienced research scientist to join our team of basic and #translational researchers working on new therapies for #neurodegenerative diseases. tinyurl.com/wa46hxye #neurotwitter #neurojobs #prion #tau #amyloid

Good science doesn't use statistics to get a yes/no answer, and before spending billions we ought to be pretty sure a drug works. Binary tests should have an obvious result. nyti.ms/3x2P1tx

Congratulations to Michael Heneka!

Congratulations to #CAND PI @saelicesl (a.k.a. Lorena Saelices, Ph.D.) for receiving a prestigious American Heart Association grant to study #ATTR #amyloidosis. She is figuring out how to discriminate distinct #TTR #fiber #polymorphs for better #therapy.