ResearchOverview
The Shaughnessy Lab investigates the physiological mechanisms that support epithelial transport processes, endocrine signaling pathways, and environmental adaptation, across diverse vertebrate systems and macroevolutionary timescales. Our work integrates molecular, cellular, and whole-organism approaches, with a particular emphasis on ion transport, hormonal signaling, and stress physiology. Research in the lab spans both fundamental and applied questions, and is organized around three complementary themes: Comparative Physiology, which examines the evolution and regulation of physiological systems across taxa; Applied Physiology, which addresses conservation or industry needs by contributing physiological insights; and Translational Physiology, which focuses on epithelial transport and CFTR function in the context of human disease.
ComparativePhysiology
Our research in this theme is centered on processes of environmental physiology and the endocrine programs that regulate them. We integrate in vivo, ex vivo, and in vitro approaches and focus our attention primarily to processes of ionoregulation, stress, and thermal tolerance. Although the majority of our studies have centered on fishes, past and ongoing work also includes studies on crustaceans and amphibians. Given that we work heavily on basal lineages of fishes (i.e., hagfishes, lampreys, elasmobranchs, and non-teleosts), a major emphasis of this work that has emerged is in understanding how complexity in physiological processes evolved throughout the radiation of vertebrates, including how endocrine signaling systems or epithelial transport processes gained or lost function through genome evolutionary events. This research is deeply integrated in a broader community of comparative physiology and endocrinology, and we regularly present our work at meetings such as the International Congress on the Biology of Fish (ICBF), the North American Society for Comparative Endocrinology (NASCE), as well as other meetings less frequently.
Comparative | Epithelial Ion Transport and Osmoregulation
This research focuses on how aquatic vertebrates regulate salt and water balance through epithelial ion transport. We investigate the function of ionocytes (i.e., specialized cells that mediate epithelial ion movements) in the gill and intestinal tract and the hormonal signals that modulate their presence and activity during developmental and environmental changes. Our investigations combine organismal experiments with molecular, histological, and electrophysiological analyses to examine ionoregulatory mechanisms. By combining molecular and functional approaches in both model and non-model fishes, we explore the diversity and plasticity of osmoregulatory physiology in vertebrates. These comparative studies aim to understand how varied ion transport strategies enable ecological transitions (e.g., movement between fresh and salt water) and evolved throughout the radiation of vertebrates.
Ongoing Projects
- Elucidating the functional role of Ano1 in the SW-type ionocyte of diverse marine fishes
- Exploring acid-base linked Na+ and Cl- tranport processes in the intestinal tract in sea lamprey
- Identifying and characterizing the K+ channel in SW-type ionocyte in the sea lamprey gills
- Examining the role of AVP and related peptides in controlling intestinal ion transport in lampreys and teleosts
Selected Papers
A Cftr-independent, Ano1-rich seawater-adaptive ionocyte in sea lamprey gills
Shaughnessy CA, Hall DJ, Norstog JL, Ferreira-Martins D, Barany A, Regish AM, Breves JP, Komoroske LM, McCormick SD
Endocrine control of gill ionocyte function in euryhaline fishes
Breves JP, Shaughnessy CA
Functional characterization and osmoregulatory role of gill Na+/K+/2Cl- cotransporter (NKCC1) in sea lamprey (Petromyzon marinus), a basal vertebrate
Shaughnessy CA, McCormick SD
Comparative | Evolution of Neuroendocrine Signaling Pathways
This research investigates the functional evolution of neuroendocrine signaling pathways in early vertebrates. We focus primarily on the hypothalamus-pituitary-adrenal/interrenal (HPA/HPI) axis, including the melanocortin (Acth/Msh) and corticotropin-releasing hormone (Crh) signaling systems. We examine how functional diversity of ligands and receptors in these systems emerged across the radiation of vertebrates. Our work combines manipulative physiological experiments (e.g., administration of hormones or receptor antagonists) with in vitro experimentation and molecular analyses (e.g., cloning, heterologous expression in mammalian systems, pharmacological characterization, and evolutionary genetics). Through these approaches, we explore the physiological role(s) of these neuroendocrine pathways in basal vertebrates, the evolution of receptor function (e.g., ligand-receptor specificity and cell signaling interactions), and the expansion, diversification, and specialization of endocrine gene families. Our comparative studies in basal fishes aim to further our understanding of how changes in receptor architecture and regulatory elements contributed to the emergence of endocrine complexity in vertebrates.
Ongoing Projects
- Functional characterization of hagfish melanocortin receptors
- Discovery of novel melanocortin ligands in agnathans
- Exploring the functional evolution of the Crh receptor family in vertebrates
- Characterizing the HPI axis in agnathans
Selected Papers
Functionally divergent melanocortin receptor subtypes and the HPI axis in sea lamprey
Shaughnessy CA, Myhre VD, McCormick SD, Dores RM
Functional characterization of melanocortin 2 receptor (Mc2r) from a lobe-finned fish (Protopterus annectens) and insights into the molecular evolution of melanocortin receptors
Shaughnessy CA, Le K, Myhre VD, Dores RM
Hypothalamus–pituitary–interrenal (HPI) axis signaling in Atlantic sturgeon (Acipenser oxyrinchus) and sterlet (Acipenser ruthenus)
Shaughnessy CA, Myhre VD, Hall DJ, McCormick SD, Dores RM
AppliedPhysiology
Our applied physiology research leverages fundamental principles of comparative physiology to address real-world challenges in conservation, aquaculture, and fisheries management. We study how animals physiologically respond to environmental change and stress, and use this knowledge to inform practices that support the sustainability of natural and managed populations. This includes developing experimental tools and physiological biomarkers for assessing tolerance, performance, and resilience in native and invasive species. Our work often involves collaborations with agencies and stakeholders and seeks to produce insights that can be translated into actionable outcomes for biodiversity preservation, invasive species control, and habitat management.
Applied | Physiological Responses to Environmental Stress
This research focuses specifically on the stress component of environmental physiology, with particular emphasis on thermal stress, salinity stress, and the physiological effects of chronic stress from adverse environmental conditions. We study how endocrine systems, such as corticosteroid signaling, regulate or result from adaptive stress responses to ecological or environmental challenges. We also examine the role of hepatic metabolism as a downstream effector of corticosteroid action, particularly in mediating energy mobilization during acute and chronic stress. Our approach integrates organismal experiments (e.g., chronic stress paradigms, heat shock and CTmax trials), endocrine profiling, and molecular and biochemical analyses (e.g., Hsp expression and metabolic enzyme activities). Through these efforts, we aim to understand how stress tolerance and endocrine function vary across taxa, populations, and environmental contexts.
Ongoing Projects
- Producing a broadly applicable experimental paradigm to induce a chronic stress phenotype in teleosts
- Examining the thermal tolerance and HSP response to warming in sea lamprey
- Characterizing the carbohydrate metabolic responses to acute stress in pacific hagfish
- Producing an ELISA-based assay for measuring 11-deoxycortisol in lampreys
Selected Papers
11-Deoxycortisol is a stress responsive and gluconeogenic hormone in a jawless vertebrate, the sea lamprey (Petromyzon marinus)
Shaughnessy CA, McCormick SD
Upper thermal tolerance and heat shock protein response of juvenile American shad (Alosa sapidissima)
Bayse S*, Shaughnessy CA*, Regish A, McCormick SD
Reduced thermal tolerance during salinity acclimation in brook trout (Salvelinus fontinalis) can be rescued by prior treatment with cortisol
Shaughnessy CA, McCormick SD
Applied | Physiology in Conservation and Aquaculture
This research produces and applies physiological tools to understand or predict how aquatic vertebrates respond or adapt to changing or stressful environmental conditions, particularly in conservation and aquaculture contexts. We investigate how thermal, osmotic, and seasonal stressors affect the performance and survival of native, invasive, introduced, or cultured species. Projects in this area include the integration of physiological experiments with ecological modeling to evaluate environmental limits, identify management-relevant biomarkers, and characterize intraspecific variation in physiological responses environmental pressures. This work often involves collaboration with ecologists, aquaculturists, and conservation agencies (inlcuding the Oklahoma Department of Wildlife Conservation and the Great Lakes Fishery Commission) focused on population ecology, ecophysiology, species resilience,invasive species control, environmental adaptation, or sustainable agriculture.
Ongoing Projects
- Exploring the genetic basis for thermal tolerance of endemic and introduced black bass in the Ozarks
- Mechanistically investigating how adaptive thermal tolerance facilitates range expansion in green tree frog
- Evaluating the physiological effects of warming on juvenile sea lamprey in relation to migratory behavior
Selected Papers
Physiological and morphological traits affect contemporary range expansion and implications for species distribution modeling in an amphibian species
Edwards OM, Reichert MS, Ozmen L, Shaughnessy CA, Zhai L, Zhang B
The isosmotic point as critical salinity limit for growth and osmoregulation, but not survival, in the wolf eel Anarrhichthys ocellatus
Shaughnessy CA, Balfry SK, Bystriansky JS
Juvenile sea lamprey (Petromyzon marinus) have a wide window of elevated salinity tolerance that is eventually limited during springtime warming
Shaughnessy CA, McCormick SD
TranslationalPhysiology
Our translational work focuses on epithelial ion transport and CFTR regulation in the context of cystic fibrosis. This research leverages in vitro airway epithelial models and electrophysiological techniques to investigate the molecular mechanisms of CFTR function and pharmacological modulation. While our lab does not directly aim to develop therapies, our goal is to contribute to the foundational understanding of epithelial signaling and CFTR function in ways that may inform therapeutic innovation. This work connects us with the broader cystic fibrosis research community, particularly through collaborations and scientific exchange supported by the Cystic Fibrosis Foundation (CFF) and the Oklahoma Center for Respiratory and Infectious Diseases (OCRID). We also engage with research presented at the North American Cystic Fibrosis Conference (NACFC) and related professional meetings.
Translational | Mechanisms and Airway Epithelial Ion Transport
This research explores the basic mechanisms that govern ion transport across the airway epithelium, with an emphasis on the cAMP/PKA activated Cl- channel, CFTR. We investigate how cellular and epithelial context, including cell type, ionic environment, and signaling pathways, shapes ion channel function and regulation. Our studies use various cultured human airway epithelial cells and apply electrophysiological and biochemical techniques to analyze regulation of cellular signaling and ion transport activity. We also consider the molecular and functional evolution of the CFTR protein. This work aims to improve our understanding of how epithelial signaling and cellular context influence ion homeostasis in both normal and disease states, including cystic fibrosis (CF).
Ongoing Projects
- Identifying endogenous GPCR-mediated pathways that regulate CFTR activity in airway epithelial cells
- Characterizing the voltage-dependent regulation of CFTR in human airway epithelia
Selected Papers
Down-regulation of the epithelial sodium channel (ENaC) in human airway epithelia in response to low temperature incubation
Yadav S*, Shaughnessy CA*, Zeitlin PL, Bratcher PE
Effect of apical chloride concentration on the measurement of responses to CFTR modulation in airway epithelia cultured from nasal brushings
Bratcher PE, Yadav S, Shaughnessy CA, Thornell IM, Zeitlin PL
Nasal epithelial cell cultures from nasal polyps are more responsive to CFTR modulators than cultures from healthy sinuses
Shaughnessy CA, Yadav S, Zeitlin PL, Bratcher PE
Translational | Exploring Novel Insights into CFTR Modulation
This research investigates how pharmacological modulators of CFTR affect osmoregulatory function in airway epithelial models. We focus on understanding the mechanisms by which compounds like elexacaftor, tezacaftor, and ivacaftor alter CFTR activity, alone or in combination with novel co-modulators. Using in vitro experimentation, cAMP detection, and electrophysiological assays, we assess synergistic responses, receptor-mediated pathways, and the context-dependence of modulator action across different epithelial models. While this work is exploratory and not directly therapeutic, it aims to provide mechanistic insights that contribute to the broader understanding of CFTR pharmacology in the context improving therapy for of cystic fibrosis.
Ongoing Projects
- Mechanistically exploring the synergistic effects of next-generation modulators on CFTR function in primary airway epithelial cultures
- Investigating novel co-modulators and their impact on cAMP signaling and CFTR activation
- Characterizing receptor-mediated pathways that modulate CFTR activity across diverse epithelial models
Selected Papers
Receptor-mediated activation of CFTR via prostaglandin signaling pathways in the airway
Shaughnessy CA, Yadav S, Bratcher PE, Zeitlin PL
Elexacaftor is a CFTR potentiator and acts synergistically with ivacaftor during acute and chronic treatment
Shaughnessy CA, Zeitlin PL, Bratcher PE
Net benefit of ivacaftor during prolonged tezacaftor/elexacaftor exposure in vitro
Shaughnessy CA, Zeitlin PL, Bratcher PE