About

The Albrecht Laboratory is dedicated to uncovering the role of methylation in signal transduction, cellular metabolism, and human disease.

Research topics

• Biochemistry
• Cell biology
• Biology
• Computer Science
• Chemistry
• Genetics

Selected publications

• PFKM governs metabolic shifts throughout skeletal muscle differentiation

  Nature Metabolism · 2026-02-24 · 2 citations

  articleOpen accessSenior author

  Metabolism is known to influence cell identity, but the underlying mechanisms remain unclear. Here we reveal spatiotemporal dynamics of phosphofructokinase 1 (PFK1), a key glycolytic enzyme, within the skeletal muscle lineage. The expression of PFKM (the muscle isoform of PFK1) is low in muscle stem cells and increases during differentiation. Mechanistically, Wnt signalling rapidly induces lysosomal degradation of PFKM through a methyl arginine degron motif, which gets selectively methylated by the protein arginine methyltransferase (PRMT1) and delivered to lysosomes through microautophagy. PFKM degradation shifts glucose metabolism from glycolysis to the pentose phosphate pathway. PFKM overexpression increases glycolysis and promotes differentiation into terminally differentiated myofibres. On the other hand, PFKM knockdown blunts differentiation, which can be rescued by supplementation with the downstream glycolytic intermediate 3-phosphoglycerate. In sum, our findings highlight the importance of compartmentalized metabolism in cell fate decisions.

  PublisherDOI

• Age-Driven Lipid Remodeling Activates Lysosome-Mediated Plasma Membrane Repair

  Research Square · 2026-01-20

  preprintOpen accessSenior author
  PublisherOA PDFDOI

• Exploration of protein degradability enables fully endogenous MrTAC degraders

  Chem · 2026-03-01

  articleSenior author
  PublisherDOI

• Designing the Proteome with Chemical Tools: Degrons and Beyond

  ChemBioChem · 2025-05-21 · 1 citations

  reviewSenior authorCorresponding

  Cell biology relies on precise changes in protein stability, which can be chemically harnessed to transform cell fate. Decades of research have revealed the many intricate systems underlying cellular proteostasis, which can be hijacked by proximity-based degrader compounds. The archetypal degrader, proteolysis targeting chimera, recruits E3 ligases to protein targets to facilitate their ubiquitination and degradation in the proteasome. Being able to customize the human proteome with chemical tools has great value for fundamental research and for clinical progress through the controlled elimination of disease-causing proteins. Success within the degrader field has reinvigorated interest in mapping the mechanisms underlying native protein degradation, which has platformed new degrader classes capable of advancing the field toward the goal of degrading the entire human proteome. This review discusses ongoing strategies to identify degrons regulating native protein turnover, advances in chemical tools to activate these degrons, and new attempts to streamline degron pathways for simplified targeted protein degradation. The continued discovery and application of degrons has the power to transform human biology and combat disease.

  PublisherDOI

• ByeTAC: Bypassing E-Ligase-Targeting Chimeras for Direct Proteasome Degradation

  Journal of Medicinal Chemistry · 2025-04-19 · 19 citations

  article

  The development of targeted protein degradation by recruiting a protein of interest to a ubiquitin ligase to facilitate its degradation has become a powerful therapeutic tool. The potential of this approach is limited to proteins that can be readily ubiquitinated and relies on having a ligand with the various E3 ligases. Here, we describe a new methodology for targeted protein degradation that directly recruits a protein of interest to the proteasome for degradation. We generated bifunctional molecules that incorporate a small molecule ligand into a subunit on the 26S proteasome that recruits the protein directly for degradation. ByeTAC degradation requires binding to Rpn-13, a nonessential ubiquitin receptor of the 26S proteasome, and the protein of interest and does not have to rely on the E ligase cascade for ubiquitination. The ByeTAC methodology demonstrates the application of directly recruiting a protein to the proteasome via interactions with Rpn-13 for degradation.

  PublisherDOI

• TH5487 specifically targets NLRP3 in FCAS patients resistant to MCC950

  Communications Biology · 2025-06-09 · 2 citations

  preprintOpen access

  ABSTRACT The NLRP3 inflammasome plays a central role in innate immunity and is activated in response to mitochondrial dysfunction and oxidized DNA. Here, we demonstrate that repurposed small-molecule inhibitors originally developed for DNA glycosylases, TH5487 and SU0268, potently inhibit NLRP3 activation ex vivo in human Peripheral Blood Mononuclear Cells (PBMCs) with IC 50 of 1.62 µM and 3.24 µM, respectively. We show that these inhibitors prevent mitochondrial localization of NLRP3 and directly block inflammasome assembly. They also reshape the immune landscape decreasing IL-1β, while increasing IFN-β. Structural and biophysical analyses reveal a two-site DNA binding model in which NLRP3 engages oxidized DNA with a KD1 of 0.268 nM and KD2 3.02 nM. Importantly, these inhibitors block IL-1β secretion in L353P Familial Cold Autoinflammatory Syndrome (FCAS) patient PBMCs where MCC950 fails, demonstrating the therapeutic potential for inflammasome-driven diseases. Together, our findings reveal a novel druggable mechanism of inflammasome inhibition through interference with oxidized DNA sensing and localization, offering new opportunities for treatment of chronic inflammatory disorders.

  PublisherOA PDFDOI

• Methylarginine targeting chimeras for lysosomal degradation of intracellular proteins

  Nature Chemical Biology · 2024 · 23 citations

  Senior authorCorresponding
  • Computer Science
  • Cell biology
  • Chemistry
  PublisherDOI

• Sclerostin and Wnt Signaling in Idiopathic Juvenile Osteoporosis Using High-Resolution Confocal Microscopy for Three-Dimensional Analyses

  Children · 2024-07-04 · 2 citations

  articleOpen accessSenior authorCorresponding

  BACKGROUND: Idiopathic juvenile osteoporosis (IJO) is a rare condition characterized by low bone mass that can increase the risk of fractures in children. Treatment options for these patients are limited as the molecular mechanisms of disease initiation and progression are incompletely understood. Sclerostin inhibits canonical Wnt signaling, which is important for the bone formation activity of osteoblasts, and elevated sclerostin has been implicated in adult osteoporosis. OBJECTIVE: To evaluate the role of sclerostin in IJO, high-resolution confocal microscopy analyses were performed on bone biopsies collected from 13 pediatric patients. METHODS: Bone biopsies were stained with sclerostin, and β-catenin antibodies showed elevated expression across osteocytes and increased sclerostin-positive osteocytes in 8 of the 13 total IJO patients (62%). RESULTS: Skeletal sclerostin was associated with static and dynamic histomorphometric parameters. Further, colocalization analyses showed that bone sclerostin colocalized with phosphorylated β-catenin, a hallmark of Wnt signaling that indicates Wnt inhibition. In contrast, sclerostin-positive osteocytes were not colocalized with an "active" unphosphorylated form of β-catenin. CONCLUSIONS: These results support a model that altered levels of sclerostin and Wnt signaling activity occur in IJO patients.

  PublisherDOI

• Sclerostin and Wnt Signaling in Idiopathic Juvenile Osteoporosis

  SSRN Electronic Journal · 2023-01-01

  preprintOpen accessSenior author
  PublisherDOI

• Sclerostin, Osteocytes, and Wnt Signaling in Pediatric Renal Osteodystrophy

  Nutrients · 2023-09-25 · 9 citations

  articleOpen accessSenior authorCorresponding

  The pathophysiology of chronic kidney disease-mineral and bone disorder (CKD-MBD) is not well understood. Specific factors secreted by osteocytes are elevated in the serum of adults and pediatric patients with CKD-MBD, including FGF-23 and sclerostin, a known inhibitor of the Wnt signaling pathway. The molecular mechanisms that promote bone disease during the progression of CKD are incompletely understood. In this study, we performed a cross-sectional analysis of 87 pediatric patients with pre-dialysis CKD and post-dialysis (CKD 5D). We assessed the associations between serum and bone sclerostin levels and biomarkers of bone turnover and bone histomorphometry. We report that serum sclerostin levels were elevated in both early and late CKD. Higher circulating and bone sclerostin levels were associated with histomorphometric parameters of bone turnover and mineralization. Immunofluorescence analyses of bone biopsies evaluated osteocyte staining of antibodies towards the canonical Wnt target, β-catenin, in the phosphorylated (inhibited) or unphosphorylated (active) forms. Bone sclerostin was found to be colocalized with phosphorylated β-catenin, which suggests that Wnt signaling was inhibited. In patients with low serum sclerostin levels, increased unphosphorylated "active" β-catenin staining was observed in osteocytes. These data provide new mechanistic insight into the pathogenesis of CKD-MBD and suggest that sclerostin may offer a potential biomarker or therapeutic target in pediatric renal osteodystrophy.

  PublisherOA PDFDOI

Recent grants

• Wnt Signaling and Endosomal Trafficking as Regulators of Cellular Protein Degradation

  NIH · $118k · 2017–2019

Frequent coauthors

• Edward M. De Robertis

  University of California, Los Angeles

  22 shared

• Nydia Tejeda‐Muñoz

  University of California, Los Angeles

  17 shared

• Renata C. Pereira

  University of California, Los Angeles

  9 shared

• Isidro B. Salusky

  University of California, Los Angeles

  9 shared

• Maggie H. Bui

  University of California, Los Angeles

  9 shared

• Gabriele Colozza

  Institute of Molecular Biotechnology

  6 shared

• Kathleen J. Noche

  University of California, Los Angeles

  5 shared

• Alyssa Dsouza

  Wayne State University

  5 shared

Labs

• Albrecht LaboratoryPI

Education

• Postdoctoral Researcher , Biological Chemistry

  University of California Los Angeles

  2021

• PhD, Pathology

  Northwestern Medicine

  2016

• BS, Chemistry

  University of California, San Diego

  2010