Ryan Weiss

Mapping Out the “Everything” of Protein Secretion The invention of CRISPR and DNA sequencing has provided the necessary tools for rapidly engineering CHO cells along with a parts list.

Honored to have our recent work on mapping out the cell machinery regulating protein secretion highlighted at GEN www.genengnews.com/topics/biopr...

Please share my 1 min video on the importance of maintaining NIH funding of infectious diseases and drug discovery research vs rising antibiotic resistance

Drastic budget cuts harm our health and imperil the next generation of scientists

More @UCSanDiego “Behind Every Breakthrough” bit.ly/3FlXQs3

Quantitative HILIC-Q-TOF-MS Analysis of Glycosaminoglycans and Non-reducing End Carbohydrate Biomarkers via Glycan Reductive Isotopic Labeling Glycosaminoglycans (GAGs) are linear, heterogeneous polysaccharides expressed on all animal cells. Sulfated GAGs, including heparan sulfate (HS) and chondroitin/dermatan sulfate (CS/DS), are involved in numerous physiological and pathological processes; therefore, precise and robust analytical methods for their characterization are essential to correlate structure with function. In this study, we developed a method utilizing hydrophilic interaction liquid chromatography coupled with time-of-flight mass spectrometry (HILIC-Q-TOF-MS) and glycan reductive isotopic reducing end labeling (GRIL) for the quantitative compositional analysis of HS and CS/DS polysaccharides. Lyase-generated disaccharides and commercial standards were chemically tagged on the reducing end with aniline stable isotopes, thus enabling the absolute quantification of HS and CS/DS disaccharides in complex biological samples. In addition, we adapted this workflow, in conjunction with new synthetic carbohydrate standards, for the quantification of disease-specific non-reducing end (NRE) carbohydrate biomarkers that accumulate in patients with mucopolysaccharidoses (MPS), a subclass of lysosomal storage disorders. As a proof of concept, we applied this method to measure NRE biomarkers in patient-derived MPS IIIA and MPS IIID fibroblasts, as well as in cortex tissue from a murine model of MPS VII. Overall, this method demonstrates improved sensitivity compared to previous GRIL-LC/MS techniques and, importantly, avoids the use of ion-pairing reagents, which are undesirable in certain mass spectrometry instrumentation and contexts. By combining the benefits of HILIC separation with isotopic labeling, our approach offers a robust and accessible tool for the analysis of GAGs, paving the way for advancements in understanding GAG structure and function.

Excited to share our paper @pubs.acs.org detailing a new sensitive and accessible LC-MS method for analysis of GAGs and non-reducing end (NRE) biomarkers for lysosomal storage disorders! A great collaboration w/ the Azadi and Boons groups at the CCRC!
pubs.acs.org/doi/10.1021/... #glycotime

Lysosomes play a central role in regulating ECM homeostasis by influencing intracellular and extracellular molecular turnover and degradation through their biogenesis, localization, and acidification. Lysosomal biogenesis coordinates ECM homeostasis by regulating the release of ECM-degrading enzymes, promoting autolysosome-mediated degradation, and modulating lysosomal trafficking pathways. This process affects the degradation, recycling, and assembly of ECM components. Lysosomes are equipped with motor proteins, including dynein-dynactin complexes, kinesins, and small GTPases, which facilitate their trafficking along microtubules. Lysosomal acidification is essential for the breakdown and recycling of ECM components internalized by endocytosis and exocytosis, ensuring proper ECM turnover and homeostasis.

New discoveries are reshaping how scientists understand the molecular connections between the extracellular matrix and lysosomes—and the resulting implications for research and therapeutics for neurodegenerative disorders.

Learn more in this #ScienceSignaling Review: scim.ag/4kG61io

NIH staff break ranks in open letter to Director Jay Bhattacharya Bethesda Declaration urges reversal of recent policies, including funding cuts

Article by @cenmag.bsky.social on the #BethesdaDeclaration by NIH scientists and staff released earlier this morning:

cen.acs.org/policy/resea...

First Patient Treated with Personalized CRISPR Therapy, Developed in Just Six Months The first on-demand CRISPR therapy for an infant with a rare metabolic disease developed by the IGI and collaborators around the world.

This is what can be achieved today due to longstanding federal support of academic basic science alongside close partnership of universities, private industry and NIH intramural initiatives. An ecosystem worth not just saving but doubling down on!

innovativegenomics.org/news/first-p...

This is utter madness. Harvard University and its many associated academic teaching hospitals have had all federal grants terminated. How anyone could support an administration that is committing such self harm to their country is unfathomable. view.u.hms.harvard.edu?qs=3ed8c01b9...

This is particularly awful

The F awards are US biomedical workforce training awards

Their agenda to destroy the future of biomedical science on full display here

SARS-CoV-2 infectivity can be modulated through bacterial grooming of the glycocalyx | mBio Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019, can infect the gastrointestinal (GI) tract, and individuals who exhibit GI symptoms of...

While our first discovery of this occurred just weeks into the shutdown, it's great to see it off bioRxiv now.
SARS-CoV-2 infectivity can be modulated through bacterial grooming of the glycocalyx. Great collab with Knight and Esko labs and many others #glycotime
journals.asm.org/doi/10.1128/...

Comparison of Research Spending on New Drug Approvals by the NIH vs the Pharmaceutical Industry This cross-sectional study examines National Institutes of Health and pharmaceutical industry investments in recent drug approvals.

99% of new medicines developed by the pharmaceutical industry depend on NIH research jamanetwork.com/journals/jam...

Glycocalyx dysregulation impairs blood–brain barrier in ageing and disease - Nature Disruption of mucin-domain glycoprotein expression and function in the endothelial glycocalyx are associated with ageing and Alzheimer’s disease, leading to dysregulated blood–brain barrier function.

Happy to share this new #glycotime work with collaborator Tony Wyss-Coray, led by grad student Sophia Shi, mucin loss at the BBB is associated with aging and cognitive decline, can be reversed by restoration with with gene therapy. Aging is a mucinopathy!

www.nature.com/articles/s41...

Imagine if @aoc @sanders.senate.gov , every dem, SIMULTANEOUSLY held Town Halls where they allowed grant and contract recipients to explain to the country what it is they do and why it's important

Invite all media. Including RW podcasters. @spaces Flood the zone

Call it a Day Of Transparency

As a leader in my lab & various initiatives, I’ve made my stance clear....my commitment to DEI is unwavering. I won’t back down or shy away, even as others do. I’ll continue to uphold and advocate for these values.

My institution sent out something very short and not saying much. It is pretty clear that red states are planning to ride the coattails of the legal actions of blue state AGs. But red state universities/faculty/researchers/staff are absolutely freaking out rn.

New review on structural glycobiology in glycosciences: "From enzymes to organelles". Carbohydrate processing enzymes, glycosylation networks in vitro, Cryo-ET in direct visualisation of native biology , challenges for studying glycosylation by cryo-ET.
tinyurl.com/4jnv85xt

#glycotime

Screening the human miRNA interactome reveals coordinated up-regulation in melanoma, adding bidirectional regulation to miRNA networks Analysis of ST3GAL1/2 and CD98hc regulation by miRNA reveals co–up-regulation, adding a bidirectional twist to miRNA networks.

Proud of @faezehjame.bsky.social and our latest paper on upregulation by #miRNA. miRNA upregulate protein expression of CD98hc, ST3GAL1 and ST3GAL2 in a coordinated manner. Regulation is bidirectional, changing the picture on how these #RNA work. #glycotime
www.science.org/doi/10.1126/... 🧪

Rare germline structural variants increase risk for pediatric solid tumors Pediatric solid tumors are a leading cause of childhood disease mortality. In this work, we examined germline structural variants (SVs) as risk factors for pediatric extracranial solid tumors using germline genome sequencing of 1765 affected children, ...

Large-scale changes in the genome inherited from parents are significant risk factors for pediatric solid tumors, a new Science study finds. The results provide new insights into the genetic underpinnings of pediatric cancers.

That time when antivaxxers thought so hard that they accidentally re-invented vaccines.

I’m in! Thanks Amulya!