About

Dr. Siobhan Malany is an Associate Professor in the Department of Cellular and Systems Pharmacology at the University of Florida College of Pharmacy. Her research focuses on developing improved in vitro cell-based systems to better predict human drug efficacy, particularly for age-related diseases such as sarcopenia. She leverages patient-specific cells in combination with phenotypic microscopy and chemogenomic approaches to measure responses to physical stressors, and advances receptor target-based platforms using receptor-specific and selective ligands to understand drug modes of action. Her laboratory is funded by the NIH-NCATS Tissue Chip Program to develop a microphysiological system for age-related muscle wasting, utilizing patient-specific muscle primary cells in 3D culture integrated into a millifluidic device, which is placed on the International Space Station for research on microgravity effects and aging. Dr. Malany holds a Ph.D. in organic chemistry from the University of Iowa and completed postdoctoral training in pharmacology at the University of California, San Diego. Her career began in the biotechnology industry in San Diego before moving to Florida in 2011 to lead a chemical biology drug discovery team at the Sanford Burnham Chemical Genomics Center in Orlando. She became interested in space research after networking with Space Florida and CASIS, leading to her founding Micro-gRx in 2015 with seed funding from Space Florida. Her work includes launching a human muscle cell system to the ISS in 2018 and engineering a 'Human muscle-on-Chip' that was also sent to the ISS in December 2020 to study the effects of microgravity on muscle biology. She has been featured in media outlets such as Channel 6 news, Authority Magazine, Radio Cade, and the Johnson Space Center's podcast, highlighting her contributions to space-related biomedical research.

Research topics

• Biology
• Cell biology
• Biochemistry
• Medicine
• Pharmacology
• Endocrinology
• Biotechnology
• Internal medicine
• Chemistry
• Biophysics
• Engineering
• Pathology
• Cancer research
• Astrobiology
• Computational biology
• Aerospace engineering

Selected publications

• Comparative Analysis of Matrigel and Tunable Collagen‐Fibrin Blends for in Vitro Skeletal Muscle Models

  Journal of Biomedical Materials Research Part A · 2026-02-01

  article

  ABSTRACT In this study, we describe the gelation kinetics, cytocompatibility, and mechanical properties of interpenetrating networks of collagen (COL), fibrin (FIB), hyaluronan (HA), and laminin (LAM) to evaluate their potential to produce mature skeletal muscle tissue. Skeletal muscle is a dynamic tissue that relies on the fusion of myoblasts into multinucleated myofibers to maintain homeostasis. In progressively degenerative conditions, impaired myoblast fusion leads to skeletal muscle atrophy and significant mass loss. Three‐dimensional (3D) in vitro models for skeletal muscle disease have been developed to better understand disease mechanisms and facilitate drug screening. However, most rely on Matrigel, a tumor‐derived matrix that supports robust cell growth but has limited clinical relevance. To address this limitation, we focused on creating natural, multi‐component scaffolds specifically tailored for muscle applications with clinically relevant drug testing use. Using spectrophotometry and rheology, we characterized the gelation kinetics and viscoelastic properties of interpenetrating networks with varying mass ratios of COL to FIB, supplemented with fixed proportions of HA and LAM. Tunable gelation was achieved within a range of 10 to 16 min. Cytocompatibility studies with C2C12 murine myoblasts demonstrated favorable cell viability in 1:1 and 1:2 (w/w) COL:FIB blends incorporating HA and LAM. Immunostaining of differentiated C2C12 cells confirmed Myosin 4 Monoclonal Antibody (MF‐20) expression in these blends when seeded into polydimethylsiloxane (PDMS)‐anchored bundles. Notably, in cell‐laden 1:1 COL:FIB gels with a seeding density of 10 × 10 6 cells/mL, the compressive modulus increased three‐fold between days 4 and 7 of differentiation. These findings highlight the potential of COL:FIB interpenetrating networks, enhanced with HA and LAM, as promising scaffolds for developing clinically relevant models of skeletal muscle tissue.

  PublisherDOI

• Extracellular vesicle transcriptomic analysis to investigate muscle adaptation in microgravity

  iScience · 2026-04-24

  articleOpen accessSenior author
  PublisherDOI

• Tomatidine Attenuates Inflammatory Responses to Exercise-Like Stimulation in Donor-derived Skeletal Muscle Myobundles

  Medical Research Archives · 2025-01-01 · 4 citations

  articleOpen accessSenior author

  Donor-derived myotubes offer a pre-clinical model for studying muscle biology, the effects of exercise-like electrical stimulation, and assessing drug efficacy and toxicity. We engineered a 3D muscle microphysiological system from myoblasts isolated from vastus lateralis of young and older adults. Over a three-week differentiation process, we applied two cycles of low frequency electrical stimulation daily for seven days generating functional, mature myobundles, as confirmed by gene expression profiling. Both young- and old-derived myobundles showed synchronous contraction in response to electrical stimulation, however, the contraction magnitude was reduced in old-derived myobundles compared to young-derived myobundles. We then assessed the donor-specific response to tomatidine, a steroidal alkaloid found in the skin of green tomatoes, known to inhibit muscle atrophy and promote skeletal muscle hypertrophy. Bioinformatic analyses revealed that infusion of tomatidine during electrical stimulation modulated the IL-6/JAK/STAT3 pathway. The contraction magnitude decreased in the young-derived myobundles treated with tomatidine compared to vehicle-treated controls, while no significant difference was observed in the old-derived myobundles. Secretome analysis revealed age-related changes in secreted proteins linked to inflammation and extracellular matrix remodeling. Notably, tomatidine attenuates the inflammatory and extracellular matrix remodeling responses in the myobundles triggered by electrical stimulation, partially preventing the secretion of proinflammatory proteins. This intervention strategy helps balance muscle adaptation and repair, while limiting excessive proinflammatory responses. Our microphysiological system provides a valuable platform for investigating signaling pathways involved in muscle function, and pharmacological responses, advancing the understanding of age-related muscle biology.

  PublisherOA PDFDOI

• Microgravity Accelerates Skeletal Muscle Degeneration: Functional and Transcriptomic Insights from a Muscle Lab-on-Chip Model Onboard the ISS

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-27 · 3 citations

  preprintOpen accessSenior authorCorresponding

  ABSTRACT Microgravity accelerates skeletal muscle degeneration, mimicking aging, yet its effects on human muscle cell function and signaling remain underexplored. Using a muscle lab-on-chip model onboard the International Space Station, we examined how microgravity and electrically stimulated contractions influence muscle biology and age-related muscle changes. Our 3D bioengineered muscle model, cultured for 21 days (12 days in microgravity), included myobundles from young, active and older, sedentary individuals, with and without electrically stimulated contraction. Real-time data collected within an autonomous Space Tango CubeLab TM showed reduced contraction magnitude in microgravity. Global transcriptomic analysis revealed increased gene expression and particularly mitochondrial-related gene expression in microgravity for the electrically stimulated younger myobundles, while the older myobundles were less responsive. Moreover, a comparative analysis using a skeletal muscle aging gene expression database revealed that certain age-induced genes showed changes in expression in myobundles from the younger cohort when exposed to microgravity, whereas these genes remained unchanged in myobundles from the older cohort. Younger, electrically stimulated myobundles in microgravity exhibited higher expression of 45 aging genes involved in key aging pathways related to inflammation and immune function, mitochondrial dysfunction, and cellular stress; and decreased expression of 41 aging genes associated with inflammation, and cell growth. This study highlights a unique age-related molecular signature in muscle cells exposed to microgravity and underscores electrical stimulation as a potential countermeasure. These insights advance understanding of skeletal muscle aging and microgravity-induced degeneration, informing strategies for mitigating age-related muscle atrophy in space and on Earth.

  PublisherOA PDFDOI

• Microgravity accelerates skeletal muscle degeneration: Functional and transcriptomic insights from an ISS muscle lab-on-chip model

  Stem Cell Reports · 2025-06-26 · 8 citations

  articleOpen accessSenior author

  Microgravity accelerates skeletal muscle degeneration, mimicking aspects of aging, yet its effects on muscle cell function remain underexplored. Using a muscle lab-on-chip model onboard the International Space Station (ISS), we examined 3D-bioengineered myobundles derived from young and older adult donors under microgravity. Electrical stimulation applied intermittently to the myobundles revealed reduced contraction magnitude in microgravity and decreased protein levels of myosin heavy chain 7, a main isoform in slow-twitch muscle fibers. Transcriptomic profiling revealed active myogenesis across ground and spaceflight samples, but younger electrically stimulated myobundles displayed enhanced mitochondrial-related gene expression in microgravity, while older and non-electrically stimulated myobundles were less responsive. Comparative analysis between young and older derived myobundles identified 86 muscle-specific age-associated genes altered in microgravity, linked to inflammation, mitochondrial dysfunction, and cellular stress. These findings highlight a unique age-related molecular response in microgravity and underscores electrical stimulation as a potential countermeasure. These insights advance our understanding of muscle aging and degeneration in microgravity, guiding future therapeutic strategies.

  PublisherOA PDFDOI

• Targeting CXCR6 Disrupts β-Catenin Signaling and Enhances Sorafenib Response in Hepatocellular Carcinoma

  Cancers · 2025-11-28

  articleOpen access

  Background/Objectives: Hepatocellular carcinoma (HCC) therapies are limited by poor response, rapid resistance, and recurrence of aggressive disease. Sorafenib, a multi-tyrosine kinase inhibitor, can trigger β-catenin stabilization and activation, contributing to resistance. Overexpression of the chemokine receptor CXCR6 and its ligand CXCL16 and hyperactivation are implicated in HCC progression and β-catenin stabilization. We hypothesized that SBI-457, a small-molecule CXCR6 antagonist we developed, could disrupt CXCR6/β-catenin crosstalk and enhance sorafenib sensitivity. Methods: We tested SBI-457 alone and in combination with sorafenib in SK-Hep-1 xenograft models and a panel of human HCC cell lines. Tumor burden, β-catenin activation, and CXCR6 expression were assessed by tumor volume measurements, immunohistochemistry, Western blotting, and immunofluorescence. Soluble CXCL16 levels were quantified by ELISA, and cell death responses were evaluated using MTT assays. Results: In vivo, SBI-457 combined with sorafenib reduced normalized tumor volume by 55% compared to vehicle controls, modestly exceeding monotherapy effects, and attenuated sorafenib-induced β-catenin upregulation. In vitro, SBI-457 blocked nuclear accumulation of β-catenin and reversed sorafenib-induced increases in β-catenin levels. Enhanced cell death was observed in specific “responder” HCC cell lines (Hep-3B, SNU-398, JHH-5), which correlated with high intracellular β-catenin, secretion of soluble CXCL16, and expression of a high molecular weight form of CXCR6. In contrast, “non-responder” cell lines with conventional CXCR6 expression and low CXCL16 secretion showed no enhanced cell death response. Conclusions: CXCR6 antagonism with SBI-457 can modulate β-catenin activation and may help overcome sorafenib resistance in selected HCC models. These findings support further development of CXCR6 antagonists as single agents or combination therapies to improve treatment outcomes in HCC.

  PublisherDOI

• 513 A CTS team approach to investigate skeletal muscle diseases and countermeasures in a donor-derived bioengineered muscle platform

  Journal of Clinical and Translational Science · 2025-03-25

  articleOpen accessSenior author

  Objectives/Goals: Our team has developed a 24-well donor-derived skeletal muscle microphysiological system (MPS) to study signaling pathways associated with a variety of muscle diseases. 3D muscle will be utilized to evaluate pharmacologic interventions for these muscle conditions to improve both muscle mass and function. Methods/Study Population: In this study, muscle MPS were formed from healthy young female and male subjects. 3D muscle underwent a 21-day differentiation with an electrical stimulation (e-stim) regimen twice daily beginning on Day 14. Functional assessments in permeabilized fibers of both sexes included isometric and isotonic calcium-induced contractions, allowing for the characterization of force-pCa (-log[Ca2+]), force-velocity and force-power relationships. Samples from Day 17 and Day 21 will be assessed for pro-growth protein signaling via western blotting and a subset of samples will be analyzed by histology and microscopy for fiber type and size. Finally, culture media pre- and post-terminal e-stim on Day 21 will be collected for extracellular vesicle (EV) isolation and EVs will be assessed by standard proteomics analysis. Results/Anticipated Results: Permeabilized fibers from both sexes reproduced the well-established sigmoidal force-pCa and the curvilinear force-velocity and force-power relationships reported in native striated muscle. Maximum specific force and force-pCa relationship were not different between sexes. Isotonic contractile measurements revealed that these male and female fibers also exhibit similar force-velocity and force-power relationships. We anticipate that 3D muscles from day 17 compared to day 21 will exhibit higher levels of pro-growth protein signaling due to e-stim application and no differences in fiber type or size between sexes. Additionally, we expect that EV quantity will depend upon 3D muscle maturity and presence of e-stim. Discussion/Significance of Impact: This study demonstrates the similarities of functional characteristics and exercise (or e-stim) adaptation between native human skeletal muscle and 3D bioengineered skeletal muscle. Ultimately, this data further validates the muscle MPS system to study muscle diseases and to enhance the translation of therapeutics to clinical settings.

  PublisherOA PDFDOI

• 481 A CTS Team Approach to Investigate Skeletal Muscle Diseases and Countermeasures in a Patient-Derived Bioengineered Muscle Platform

  Journal of Clinical and Translational Science · 2024-04-01

  articleOpen accessSenior author

  OBJECTIVES/GOALS: Our team has developed a high-throughput 3D patient-derived muscle platform to study signaling pathways associated with skeletal muscle disease. This platform will be used to study pathologies of human muscle that arise from genetic mutations and processes of aging along with pharmacologic interventions to improve mass, function, and performance. METHODS/STUDY POPULATION: In the current study, 3D skeletal muscle is formed from young healthy male samples. Samples are treated with urocortin II (UCNII) or vehicle for ten days and evaluated for tissue performance. Functional assessments include real-time contraction magnitudes using digital image correlation (DIC) analysis of video collected during electrical pulse stimulation and end-point measures of initial and repeated tetanic force production. Functional measures provide indices of patient muscle synchronicity, strength, and endurance related to drug efficacy and toxicity which we will correlate to pro-growth protein signaling via Luminex. A subset of these samples will also be analyzed by histology and microscopy to assess muscle fiber density, type, and size, as well as myotube fusion index and sarcomere uniformity. RESULTS/ANTICIPATED RESULTS: We anticipate that healthy muscle treated with UCNII will have increased synchronicity and contraction magnitudes in DIC analysis throughout their seven-day electrical pulse stimulation protocol. We also expect to see sustained contraction magnitudes in DIC analysis at the end of electrical pulse stimulation indicating fatigue resistance in the drug treated group compared to no-drug control. Like our real-time DIC data, we anticipate increases to initial and sustained maximal force production in the drug treated group. We expect that drug treated muscle will present with an increased fiber density, fiber diameter, and fusion index with uniform sarcomeres. Finally, we expect heightened pro-growth signaling pathways in treated vs. controls. DISCUSSION/SIGNIFICANCE: The current study will serve as an initial investigation of the endogenous ligand UCNII for enhancing skeletal muscle mass and performance in human muscle laying the framework for future drug efficacy and toxicity studies. This platform will ultimately enhance the study of muscle diseases and translation of therapeutics to clinical settings.

  PublisherOA PDFDOI

• AI/ML Powered Commercial Grade Human Performance System Enabling Standardized Space Biotech Research and Development

  2024-01-01

  article
  PublisherDOI

• Discovery of small molecule guanylyl cyclase B receptor positive allosteric modulators

  PNAS Nexus · 2024-05-31 · 2 citations

  articleOpen accessCorresponding

  Myocardial fibrosis is a pathological hallmark of cardiovascular disease (CVD), and excessive fibrosis can lead to new-onset heart failure and increased mortality. Currently, pharmacological therapies for myocardial fibrosis are limited, highlighting the need for novel therapeutic approaches. The particulate guanylyl cyclase B (GC-B) receptor possesses beneficial antifibrotic actions through the binding of its natural ligand C-type natriuretic peptide (CNP) and the generation of the intracellular second messenger, cyclic guanosine 3',5'-monophosphate (cGMP). These actions include the suppression of fibroblast proliferation and reduction in collagen synthesis. With its abundant expression on fibroblasts, the GC-B receptor has emerged as a key molecular target for innovative CVD therapeutics. However, small molecules that can bind and potentiate the GC-B/cGMP pathway have yet to be discovered. From a cell-based high-throughput screening initiative of the NIH Molecular Libraries Small Molecule Repository and hit-to-lead evolution based on a series of structure-activity relationships, we report the successful discovery of MCUF-42, a GC-B-targeted small molecule that acts as a positive allosteric modulator (PAM). Studies herein support MCUF-42's ability to enhance the binding affinity between GC-B and CNP. Moreover, MCUF-42 potentiated cGMP levels induced by CNP in human cardiac fibroblasts (HCFs) and notably also enhanced the inhibitory effect of CNP on HCF proliferation. Together, our findings highlight that MCUF-42 is a small molecule that can modulate the GC-B/cGMP signaling pathway, potentially enhancing the antifibrotic actions of CNP. Thus, these data underscore the continued development of GC-B small molecule PAMs as a novel therapeutic strategy for targeting cardiac fibrosis and CVD.

  PublisherOA PDFDOI

Recent grants

• Novel Therapeutics for Cardiovascular Disease

  NIH · $2.8M · 2022–2026

• Electrical Stimulation of Human Myocytes in Microgravity: An In Vitro Model to Evaluate Therapeutics to Counteract Muscle Wasting

  NIH · $1.0M · 2018–2020

• Small Molecule Discovery for Particulate Guanylyl Cyclase Receptor B Enhancers

  NIH · $2.0M · 2017–2021

Frequent coauthors

• Mark Santos

  26 shared

• Sandra Lechner

  Vertex Pharmaceuticals (United States)

  25 shared

• Raymond S. Gross

  Vertex Pharmaceuticals (United States)

  25 shared

• José-Luis Díaz

  Universidad Nacional Autónoma de México

  24 shared

• M. N. Moorjani

  24 shared

• Deborah H. Slee

  Gossamer Bio (United States)

  24 shared

• Marion Lanier

  24 shared

• Satyamaheshwar Peddibhotla

  University of Florida

  24 shared

Education

• Ph.D., organic chemistry and enzymology

  University of Iowa

• Other, pharmacology

  University of California, San Diego

• Other

  Max-Planck Institute for Brain Research