About

J. Ross Buchan is an Associate Professor in the Departments of Biochemistry and Molecular & Cellular Biology, Neuroscience, Genetics, and Cancer at the University of Arizona. He is also affiliated with the GIDP and the Bio5 Institute. His office is located in Life Sciences South, Room 548A, and his laboratory spaces are in Rooms 503 and 507 of the same building. Dr. Buchan's work involves research in biochemistry, molecular and cellular biology, neuroscience, genetics, and cancer. The university recognizes his contributions within these interdisciplinary fields and emphasizes building sustainable relationships with Indigenous communities, reflecting a commitment to community engagement and education.

Research topics

• Cell biology
• Biology
• Genetics
• Computer Science
• Biochemistry
• Computational biology
• Molecular biology

Selected publications

• Rsp5/NEDD4 and ESCRT regulate TDP-43 toxicity and turnover via an endolysosomal clearance mechanism

  The Journal of Cell Biology · 2025-10-25 · 1 citations

  articleOpen accessSenior author

  A pathological hallmark in >97% of amyotrophic lateral sclerosis (ALS) cases is the cytoplasmic mislocalization and aggregation of TDP-43, a nuclear RNA-binding protein, in motor neurons. Driving clearance of cytoplasmic TDP-43 reduces toxicity in ALS models, though how TDP-43 clearance is regulated remains controversial. We conducted an unbiased yeast screen using high-throughput dot blotting to identify genes that affect TDP-43 levels. We identified ESCRT complex genes, which induce membrane invagination (particularly at multivesicular bodies; MVBs) and genes linked to K63 ubiquitination (particularly cofactors of the E3 ubiquitin ligase Rsp5; NEDD4 in humans), as drivers of TDP-43 endolysosomal clearance. TDP-43 colocalized and bound Rsp5/NEDD4 and ESCRT proteins, and perturbations to either increased TDP-43 aggregation, stability, and toxicity. NEDD4 also ubiquitinates TDP-43. Lastly, TDP-43 accumulation induces giant MVB-like vesicles, within which TDP-43 accumulates in a NEDD4-dependent manner. Our studies shed light on endolysosomal-mediated cytoplasmic protein clearance, a poorly understood proteostasis mechanism, which may help identify novel ALS therapeutic strategies.

  PublisherDOI

• Phosphorylation of an <scp>RNA</scp>‐Binding Protein Rck/Me31b by Hippo Is Essential for Adipose Tissue Aging

  Aging Cell · 2025-03-11 · 7 citations

  articleOpen access

  The metazoan lifespan is determined in part by a complex signaling network that regulates energy metabolism and stress responses. Key signaling hubs in this network include insulin/IGF-1, AMPK, mTOR, and sirtuins. The Hippo/Mammalian Ste20-like Kinase1 (MST1) pathway has been reported to maintain lifespan in Caenorhabditis elegans, but its role has not been studied in higher metazoans. In this study, we report that overexpression of Hpo, the MST1 homolog in Drosophila melanogaster, decreased lifespan with concomitant changes in lipid metabolism and aging-associated gene expression, while RNAi Hpo depletion increased lifespan. These effects were mediated primarily by Hpo-induced transcriptional activation of the RNA-binding protein maternal expression at 31B (Me31b)/RCK, resulting in stabilization of mRNA-encoding a lipolytic hormone, Akh. In mouse adipocytes, Hpo/Mst1 mediated adipocyte differentiation, phosphorylation of RNA-binding proteins such as Rck, decapping MRNA 2 (Dcp2), enhancer Of MRNA decapping 3 (Edc3), nucleolin (NCL), and glucagon mRNA stability by interacting with Rck. Decreased lifespan in Hpo-overexpressing Drosophila lines required expression of Me31b, but not DCP2, which was potentially mediated by recovering expression of lipid metabolic genes and formation of lipid droplets. Taken together, our findings suggest that Hpo/Mst1 plays a conserved role in longevity by regulating adipogenesis and fatty acid metabolism.

  PublisherOA PDFDOI

• Stress granules and P-bodies – New ideas and experimental models worth exploring

  Seminars in Cell and Developmental Biology · 2024-01-16 · 1 citations

  review1st authorCorresponding
  PublisherDOI

• Stress granule and P-body clearance: Seeking coherence in acts of disappearance

  Seminars in Cell and Developmental Biology · 2024-01-25 · 34 citations

  reviewOpen access1st authorCorresponding
  PublisherOA PDFDOI

• HARLEY mitigates user bias and facilitates efficient quantification and co-localization analyses of foci in yeast fluorescence images

  Scientific Reports · 2022-07-18 · 2 citations

  articleOpen accessSenior author

  Quantification of cellular structures in fluorescence microscopy data is a key means of understanding cellular function. Unfortunately, numerous cellular structures present unique challenges in their ability to be unbiasedly and accurately detected and quantified. In our studies on stress granules in yeast, users displayed a striking variation of up to 3.7-fold in foci calls and were only able to replicate their results with 62-78% accuracy, when re-quantifying the same images. To facilitate consistent results we developed HARLEY (Human Augmented Recognition of LLPS Ensembles in Yeast), a customizable software for detection and quantification of stress granules in S. cerevisiae. After a brief model training on ~ 20 cells the detection and quantification of foci is fully automated and based on closed loops in intensity contours, constrained only by the a priori known size of the features of interest. Since no shape is implied, this method is not limited to round features, as is often the case with other algorithms. Candidate features are annotated with a set of geometrical and intensity-based properties to train a kernel Support Vector Machine to recognize features of interest. The trained classifier is then used to create consistent results across datasets. For less ambiguous foci datasets, a parametric selection is available. HARLEY is an intuitive tool aimed at yeast microscopy users without much technical expertise. It allows batch processing of foci detection and quantification, and the ability to run various geometry-based and pixel-based colocalization analyses to uncover trends or correlations in foci-related data. HARLEY is open source and can be downloaded from https://github.com/lnilya/harley .

  PublisherOA PDFDOI

• Rsp5/NEDD4 and ESCRT regulate TDP-43 toxicity and turnover via an endolysosomal clearance mechanism

  bioRxiv (Cold Spring Harbor Laboratory) · 2022-12-05 · 3 citations

  preprintOpen accessSenior authorCorresponding

  Abstract A key pathological hallmark in &gt;97% of all Amyotrophic Lateral Sclerosis (ALS) cases is the cytoplasmic mislocalization and aggregation of a nuclear RNA binding protein, TDP-43. Driving clearance of cytoplasmic TDP-43 reduces toxicity in various ALS models, though how TDP-43 clearance is regulated remains controversial. To address this, we conducted an unbiased yeast genome-wide screen using high-throughput dot blots to identify genes that affect TDP-43 levels. Our screen identified ESCRT complex factors, which induce membrane invagination (particularly at multi-vesicular bodies; MVBs) and K63-linked ubiquitination as key facilitators of TDP-43 endolysosomal clearance. TDP-43 co-localized and bound Rsp5/NEDD4 and ESCRT proteins, and perturbations to either increased TDP-43 aggregation and accumulation. NEDD4 also ubiquitinates TDP-43. Lastly, TDP-43 accumulation caused formation of “giant” MVBs which could reflect a pathological consequence of TDP-43 pertinent to ALS. Our studies shed light on endolysosomal-mediated cytoplasmic protein degradation, which likely impacts multiple substrates, and may be a target for novel ALS therapeutic strategies.

  PublisherOA PDFDOI

• EDC3 phosphorylation regulates growth and invasion through controlling P‐body formation and dynamics

  EMBO Reports · 2021 · 45 citations

  • Cell biology
  • Biology
  • Biochemistry
  PublisherOA PDFDOI

• Correction: Fernandes et al. Stress Granule Assembly Can Facilitate but Is Not Required for TDP-43 Cytoplasmic Aggregation. Biomolecules 2020, 10, 1367

  Biomolecules · 2021-12-17

  erratumOpen accessSenior authorCorresponding

  In the original article [...].

  PublisherOA PDFDOI

• HARLEY: A Semi-Automated detection of foci in fluorescence images of yeast

  bioRxiv (Cold Spring Harbor Laboratory) · 2021-12-01

  preprintOpen accessSenior authorCorresponding

  Quantification of cellular structures in fluorescence microscopy data is a key means of understanding cellular function. Unfortunately, numerous cellular structures present unique challenges in their ability to be unbiasedly and accurately detected and quantified. In our studies on stress granules in yeast, users displayed a striking variation of up to 3.7-fold in foci calls and were only able to replicate their results with 62-78% correlation, when requantifying the same images. To facilitate consistent results we developed HARLEY (Human Augmented Recognition of LLPS Ensembles in Yeast), a customizable software for detection and quantification of stress granules in S.cerevisiae. After a brief model training on ~20 cells the detection of foci is fully automated and based on closed loops in intensity contours, constrained only by the a-priori known size of the features of interest. Since no shape is implied, this method is not limited to round features, as is often the case with other algorithms. Candidate features are annotated with a set of geometrical and intensity-based properties to train a kernel Support Vector Machine to recognize features of interest. The trained classifier is then used to create consistent results across datasets. HARLEY is aimed at users without technical expertise, allows for batch processing and is freely available, which should be of broad interest to users focused on analysis of microscopy data in yeast.

  PublisherOA PDFDOI

• RNAs as Regulators of Cellular Matchmaking

  Frontiers in Molecular Biosciences · 2021-04-09 · 20 citations

  reviewOpen accessSenior authorCorresponding

  RNA molecules are increasingly being identified as facilitating or impeding the interaction of proteins and nucleic acids, serving as so-called scaffolds or decoys. Long non-coding RNAs have been commonly implicated in such roles, particularly in the regulation of nuclear processes including chromosome topology, regulation of chromatin state and gene transcription, and assembly of nuclear biomolecular condensates such as paraspeckles. Recently, an increased awareness of cytoplasmic RNA scaffolds and decoys has begun to emerge, including the identification of non-coding regions of mRNAs that can also function in a scaffold-like manner to regulate interactions of nascently translated proteins. Collectively, cytoplasmic RNA scaffolds and decoys are now implicated in processes such as mRNA translation, decay, protein localization, protein degradation and assembly of cytoplasmic biomolecular condensates such as P-bodies. Here, we review examples of RNA scaffolds and decoys in both the nucleus and cytoplasm, illustrating common themes, the suitability of RNA to such roles, and future challenges in identifying and better understanding RNA scaffolding and decoy functions.

  PublisherOA PDFDOI

Recent grants

• Analysis of mRNP granule clearance, vacuolar RNA decay and TDP-43 turnover

  NIH · $3.0M · 2016–2027

Frequent coauthors

• Roy Parker

  Howard Hughes Medical Institute

  21 shared

• Guido Kroemer

  Centre de Recherche des Cordeliers

  8 shared

• Anna Dubrovska

  OncoRay

  7 shared

• Nils Cordes

  TU Dresden

  7 shared

• Audrey Esclatine

  Institut de Biologie Intégrative de la Cellule

  6 shared

• Matias Simons

  Heidelberg University

  6 shared

• Renaud Legouis

  Université Paris-Saclay

  6 shared

• Baharia Mograbi

  6 shared

Labs

• Buchan LabPI

  Not provided