About

Rachelle Crosbie is a Professor and Department Chair in the Department of Integrative Biology and Physiology at UCLA. She was raised in southeast Texas and spent part of her childhood in Saudi Arabia, where she learned to scuba dive, ride a camel, and survive in the Arabian desert. Her interest in research was sparked during a summer internship at M.D. Anderson Cancer Center in Houston. She completed her Ph.D. in Biochemistry at UCLA, focusing on protein biochemistry and the relationship between the structure and function of contractile proteins in skeletal muscle. Her postdoctoral research at the University of Iowa, supported by the Muscular Dystrophy Association, centered on Duchenne muscular dystrophy (DMD), where she discovered the muscle protein sarcospan, associated with dystrophin, which her lab now studies as a potential target for DMD treatment. Her research focuses on the loss of connection between muscle cell membranes and the extracellular matrix in DMD, aiming to develop strategies that utilize the muscle's own compensatory mechanisms to ameliorate dystrophic muscle. She has identified molecular events involving sarcospan that can improve muscle function in DMD, including the development of small compounds to activate sarcospan as potential treatments. Crosbie is dedicated to education, having developed online courses on DMD and leading NIH training programs for graduate students and postdoctoral fellows. Her work is supported by continuous NIH funding, and she has received numerous awards for her teaching and research contributions.

Research topics

• Biology
• Cell biology
• Medicine
• Internal medicine
• Endocrinology
• Genetics
• Pathology
• Surgery

Selected publications

• Training the next generation of transdisciplinary leaders for a sustainable future

  Cell Reports Sustainability · 2026-01-01 · 1 citations

  articleOpen access

  Training future leaders for sustainable food systems requires transdisciplinary fluency and collaboration across science, policy, and social systems. This commentary proposes a framework for graduate-level training that is designed to equip future leaders to advance transitions toward equitable and sustainable food systems through systems-level thinking and cross-sector collaboration.

  PublisherDOI

• Drp1 regulates mitochondrial health and controls skeletal muscle mass through the Erk1/2-Nur77 pathway

  Science Advances · 2026-05-08

  articleOpen access

  The maintenance of skeletal muscle mass relies on mitochondrial quality control, including balanced dynamics and mitophagy. Dynamin-related protein 1 (Drp1), a central mediator of mitochondrial fission, is essential for these processes, yet its role in muscle mass regulation remains incompletely defined. Here, we show that acute Drp1 deletion in the skeletal muscle increases Parkin-mediated mitochondrial degradation, reduces mitochondrial DNA (mtDNA) content, and leads to severe muscle atrophy. Although dual deletion of Drp1 and Parkin restores mtDNA content, muscle loss persists. Mechanistically, Drp1 loss impairs mitochondrial respiratory chain activity, suppressing extracellular signal-regulated kinase 1/2 (Erk1/2) signaling and down-regulating the nuclear receptor subfamily 4 group A member 1 (Nur77). Pharmacologic β2-adrenergic receptor activation with clenbuterol reactivated Erk1/2, restored Nur77 expression, and rescued muscle atrophy. These findings define a Drp1-Erk1/2-Nur77 signaling axis linking mitochondrial integrity to skeletal muscle mass and identify a potential therapeutic target for muscle degeneration in mitochondrial and metabolic diseases.

  PublisherDOI

• Design principles of cells for eatability and scalability of cultivated meat

  Trends in Food Science & Technology · 2026-04-03

  article
  PublisherDOI

• Assessing current and future needs for workforce development in cellular agriculture

  Industry and Higher Education · 2026-03-03

  articleOpen access

  The production of animal proteins ex vivo using approaches in cellular agriculture has potential to meet expanding global demands for sustainable and nutritious foods. Growth in the field of cellular agriculture is reflected by the emergence of companies focused on supporting the cultivation of cell-based and acellular products from animal and microbial cell lines. Accelerating research and development in cellular agriculture requires an interdisciplinary workforce that is fluent across disciplines including science, engineering, law, ethics, and behavioral science. PhD graduates who are trained in research projects specific to cellular agriculture are now emerging, but there is still a shortage of a skilled workforce that meets industry demands. Using three complementary theoretical models—human capital theory, skill formation theory and the triple helix model, and the actiotope model—we developed a framework to understand industry needs. We used this framework to develop and launch a survey for 18 cellular agriculture companies to assess their current and future workforce requirements, including the disciplinary backgrounds of future employees they are seeking to achieve their goals. We then analyzed the survey data, contextualized the findings, and summarized short-term and long-term strategies to identify educational pathways and resources that could produce candidates with cellular agriculture training and industry-readiness that match current and anticipated industry needs.

  PublisherDOI

• Sarcospan protects against LGMD R5 via remodeling of the sarcoglycan complex composition in dystrophic mice

  Journal of Clinical Investigation · 2025-06-19

  articleOpen accessSenior authorCorresponding

  The dystrophin-glycoprotein complex (DGC) is composed of peripheral and integral membrane proteins at the muscle cell membrane that link the extracellular matrix with the intracellular cytoskeleton. While it is well established that genetic mutations that disrupt the structural integrity of the DGC result in numerous muscular dystrophies, the 3D structure of the complex has remained elusive. Two recent elegant cryoEM structures of the DGC illuminate its molecular architecture and reveal the unique structural placement of sarcospan (SSPN) within the complex. SSPN, a 25 kDa tetraspanin-like protein, anchors β-dystroglycan to the β-, γ- and δ-sarcoglycan trimer, supporting the conclusions of biochemical studies that SSPN is a core element for DGC assembly and stabilization. Here, we advance these studies by revealing that SSPN provides scaffolding in δ-sarcoglycanopathies, enabling substitution of δ-sarcoglycan by its homolog, ζ-sarcoglycan, leading to the structural integrity of the DGC and prevention of limb-girdle muscular dystrophy R5. Three-dimensional modeling reveals that ζ-sarcoglycan preserves protein-protein interactions with the sarcospan, sarcoglycans, dystroglycan, and dystrophin. The structural integrity of the complex maintains myofiber attachment to the extracellular matrix and protects the cell membrane from contraction-induced damage. These findings demonstrate that sarcospan prevents limb-girdle muscular dystrophy R5 by remodeling of the sarcoglycan complex composition.

  PublisherOA PDFDOI

• Abstract Wed091: Biomechanical and Transcriptomic Remodeling of the Heart in Heart Failure with Preserved Ejection Fraction

  Circulation Research · 2025-08-01

  article

  Background: Heart failure with preserved ejection fraction (HFpEF) is induced by multiple risk factors including obesity, hypertension, diabetes, and aging, but how these individual comorbidities act synergistically to cause HFpEF is unclear. We hypothesize that obesity and hypertension cause transcriptional and epigenetic remodeling that drive heart failure progression. Methods: Adult male mice were administered high fat diet (HFD, 60% kcal from fat), L-NAME (0.5g/L) or both in combination (2-hit mouse model of HFpEF) for 15 weeks. After phenotypic characterization, we conducted RNA sequencing on isolated cardiomyocytes to identify the transcriptomic signatures of individual risk factors. We also extensively characterized extracellular matrix (ECM) remodeling through novel decellularization approaches. Results: Both L-NAME alone and HFD+L-NAME (HFpEF) mice had elevated systolic blood pressure (153.1 mmHg in HFpEF, 140.3 mmHg in L-NAME and 113.3 mmHg in control, p=0.0001) and both HFD alone and HFpEF had impaired exercise capacity (49 min in HFpEF, 35.1 min in HFD and 139 min in control, p=0.0001). Diastolic dysfunction was only observed in the HFpEF group (E/e’ -39.8 v. -24.7 in control, p=0.0001, LVEDP 18.9 mmHg v. 3.1 mmHg in control, p=0.0001). Transcriptome analyses of HFpEF, L-NAME, HFD, and control revealed that L-NAME clustered closest to the HFpEF group, suggesting hypertension is a major contributor to HFpEF pathology at 15 weeks. Downregulated gene programs were generally shared between treatment groups, including glycolysis (Eno1, Ldhb, Gapdh) and cytoskeleton organization (Actr2, RAN, Cfl2). Gene programs such as voltage gated channels (Kcnq2, Cacna1e, Cacnag4) and chemokine signaling (Cxcr2, Xcr1, Ccr2) were only upregulated in HFpEF and L-NAME groups. Activated genes shared between HFD and HFpEF related to metabolic stress (Nr4a3, Pik3r1, Pla2g4e). In addition to picrosirius histology revealing mild fibrosis, we examined key components of the ECM to characterize previously unknown remodeling of the muscle-matrix interface. We identified that the basement membrane (indicated by laminin) is significantly expanded in the HFpEF condition, concomitant with upregulation of collagens and genes coordinating ECM organization (Col26a1, Col22a1, Ltbp1). These findings reveal the development of HFpEF through the contributions of distinct risk factors and identify new features of ECM remodeling in the disease.

  PublisherDOI

• Macrophage-derived Spp1 promotes intramuscular fat in dystrophic muscle

  JCI Insight · 2025-07-07 · 10 citations

  articleOpen access

  Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disorder involving cycles of muscle degeneration and regeneration, leading to accumulation of intramuscular fibrosis and fat. Ablation of Osteopontin/Spp1 in a murine model of DMD (mdx) improves the dystrophic phenotype, but the source of Spp1 and its impact on target cells in dystrophic muscles remain unknown. In dystrophic muscles, macrophages are the predominate infiltrating leukocyte and express high levels of Spp1. We used macrophage-specific ablation combined with single-cell transcriptional profiling to uncover the impact of macrophage-derived Spp1 on cell-cell interactions in mdx muscles. Ablation of macrophage-specific Spp1 (cKO) correlated with reduction of 2 PDGFRa+ stromal cell populations, expressing Lifr+ and Procr+. Sorting and transcriptional profiling of these populations confirmed that they are enriched in adipogenesis genes and are highly related to fibroadipogenic precursors (FAPS). These adipogenic stromal cells (ASC) displayed more adipogenic potential in vitro compared with FAPS, likely due to a more differentiated state. Reduction of ASCs correlated with reduced intramuscular diaphragmatic fat and improved diaphragm function. These data suggest a role for myeloid-derived Spp1 in the differentiation of stromal cells towards an adipogenic fate, leading to accumulation of intramuscular fat in dystrophic muscles.

  PublisherDOI

• Sarcospan selectively interfaces with sarcoglycan subunits to stabilize the sarcolemma and prevent limb-girdle muscular dystrophy

  Physiology · 2025-05-01

  article1st authorCorresponding

  Skeletal muscle possesses redundant molecular mechanisms that partially or fully compensate for loss of gene function and this information has been leveraged for development of novel therapies for the muscular dystrophies. Mutations in any one of the canonical sarcoglycan genes cause autosomal recessive Limb-girdle muscular dystrophies that are characterized by life-limiting skeletal muscle wasting and weakness. The objective of this study was to investigate the orthologous relationships within the sarcoglycan proteins and use these mechanisms to design new therapies for the Limb-girdle muscular dystrophies. The sarcoglycan complex canonically consists of alpha-, beta-, delta- and gamma-subunits. We show that sarcospan, a transmembrane scaffolding protein, mediates assembly of a compensatory complex in gamma-sarcoglycan deficient muscles, where gamma-sarcoglycan is replaced by zeta-sarcoglycan, a less abundant sarcoglycan. This alternative complex significantly improved skeletal muscle pathology in mouse models of Limb-girdle muscular dystrophy. Three-dimensional structural modeling of the compensatory sarcoglycan complex reveals that zeta-sarcoglycan maintains specific hydrophobic interactions with sarcospan and preserves overall quaternary arrangement. This compensatory complex protects the cell membrane from contraction-induced damage and all secondary consequences of disease. These findings demonstrate a novel mechanism stabilizing the complex by leveraging protein redundancy, with an important role for sarcospan in assembly and scaffolding of a compensatory complex in skeletal muscles. This work is supported by Sarepta Therapeutics This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

  PublisherDOI

• Benfotiamine improves dystrophic pathology and exercise capacity in <i>mdx</i> mice by reducing inflammation and fibrosis

  Human Molecular Genetics · 2024-05-06 · 5 citations

  articleOpen access

  Duchenne Muscular Dystrophy (DMD) is a progressive and fatal neuromuscular disease. Cycles of myofibre degeneration and regeneration are hallmarks of the disease where immune cells infiltrate to repair damaged skeletal muscle. Benfotiamine is a lipid soluble precursor to thiamine, shown clinically to reduce inflammation in diabetic related complications. We assessed whether benfotiamine administration could reduce inflammation related dystrophic pathology. Benfotiamine (10 mg/kg/day) was fed to male mdx mice (n = 7) for 15 weeks from 4 weeks of age. Treated mice had an increased growth weight (5-7 weeks) and myofibre size at treatment completion. Markers of dystrophic pathology (area of damaged necrotic tissue, central nuclei) were reduced in benfotiamine mdx quadriceps. Grip strength was increased and improved exercise capacity was found in mdx treated with benfotiamine for 12 weeks, before being placed into individual cages and allowed access to an exercise wheel for 3 weeks. Global gene expression profiling (RNAseq) in the gastrocnemius revealed benfotiamine regulated signalling pathways relevant to dystrophic pathology (Inflammatory Response, Myogenesis) and fibrotic gene markers (Col1a1, Col1a2, Col4a5, Col5a2, Col6a2, Col6a2, Col6a3, Lum) towards wildtype levels. In addition, we observed a reduction in gene expression of inflammatory gene markers in the quadriceps (Emr1, Cd163, Cd4, Cd8, Ifng). Overall, these data suggest that benfotiamine reduces dystrophic pathology by acting on inflammatory and fibrotic gene markers and signalling pathways. Given benfotiamine's excellent safety profile and current clinical use, it could be used in combination with glucocorticoids to treat DMD patients.

  PublisherOA PDFDOI

• The Development of Robust Antibodies to Sarcospan, a Dystrophin- and Integrin-Associated Protein, for Basic and Translational Research

  International Journal of Molecular Sciences · 2024-06-01 · 1 citations

  articleOpen accessSenior authorCorresponding

  Sarcospan (SSPN) is a 25-kDa transmembrane protein that is broadly expressed at the cell surface of many tissues, including, but not limited to, the myofibers from skeletal and smooth muscles, cardiomyocytes, adipocytes, kidney epithelial cells, and neurons. SSPN is a core component of the dystrophin–glycoprotein complex (DGC) that links the intracellular actin cytoskeleton with the extracellular matrix. It is also associated with integrin α7β1, the predominant integrin expressed in skeletal muscle. As a tetraspanin-like protein with four transmembrane spanning domains, SSPN functions as a scaffold to facilitate protein–protein interactions at the cell membrane. Duchenne muscular dystrophy, Becker muscular dystrophy, and X-linked dilated cardiomyopathy are caused by the loss of dystrophin at the muscle cell surface and a concomitant loss of the entire DGC, including SSPN. SSPN overexpression ameliorates Duchenne muscular dystrophy in the mdx murine model, which supports SSPN being a viable therapeutic target. Other rescue studies support SSPN as a biomarker for the proper assembly and membrane expression of the DGC. Highly specific and robust antibodies to SSPN are needed for basic research on the molecular mechanisms of SSPN rescue, pre-clinical studies, and biomarker evaluations in human samples. The development of SSPN antibodies is challenged by the presence of its four transmembrane domains and limited antigenic epitopes. To address the significant barrier presented by limited commercially available antibodies, we aimed to generate a panel of robust SSPN-specific antibodies that can serve as a resource for the research community. We created antibodies to three SSPN protein epitopes, including the intracellular N- and C-termini as well as the large extracellular loop (LEL) between transmembrane domains 3 and 4. We developed a panel of rabbit antibodies (poly- and monoclonal) against an N-terminal peptide fragment of SSPN. We used several assays to show that the rabbit antibodies recognize mouse SSPN with a high functional affinity and specificity. We developed mouse monoclonal antibodies against the C-terminal peptide and the large extracellular loop of human SSPN. These antibodies are superior to commercially available antibodies and outperform them in various applications, including immunoblotting, indirect immunofluorescence analysis, immunoprecipitation, and an ELISA. These newly developed antibodies will significantly improve the quality and ease of SSPN detection for basic and translational research.

  PublisherOA PDFDOI

Recent grants

• Restoration of muscle cell adhesion to treat cardiomyopathy in muscular dystrophy

  NIH · $1.5M · 2016–2021

• Muscle Cell Biology, Pathophysiology, and Therapeutics

  NIH · $3.5M · 2016–2026

• Structure-Function Analysis of Sarcospan

  NIH · $6.9M · 2001–2025

Frequent coauthors

• Kevin P. Campbell

  University of Florida

  53 shared

• David Venzke

  University of Iowa

  44 shared

• Kathleen H. Holt

  University of Iowa

  36 shared

• Volker Straub

  Newcastle upon Tyne Hospitals NHS Foundation Trust

  33 shared

• Connie S. Lebakken

  32 shared

• Joshua R. Sanes

  Harvard University Press

  32 shared

• Jeffrey S. Chamberlain

  University of Washington

  23 shared

• Jane C. Lee

  Cornell University

  20 shared

Labs

• Rachelle Crosbie LabPI

Awards & honors

• National Academies Education Scholar
• UCLA campus-wide Chancellor’s Distinguished Teaching Award
• Coalition Duchenne Lotus Award
• Golden Test Tube Award
• Life Sciences Award for Teaching Innovation