Research in Comparative Physiology and Endocrinology

The ‘Rock Dam’ behind the S.O. Conte Anadromous Fish Research Laboratory in Turners Falls, MA

Osmoregulation and Ion Transport

One topic of where I have focused much of my research is on how fishes survive in vastly different salinities. Most fishes are iono- and osmo-regulators―they maintain a constant internal ion and water balance regardless whether they live in freshwater or seawater. The thin layers of cells in the gill and gut of fishes that form a barrier separating the fishes inside (blood) from its environment (water) are important epithelia across which fish can transport ions and water. In freshwater, fishes passively gain water and lose ions to the dilute environment, so the gill epithelium has a crucial role in ion-uptake. In seawater, fishes passively lose water (dehydrate) and gain ions from the salty environment, so the gill and gut work in tandem to absorb water in the gut and secrete excess ions from the gill. Migratory fishes which live in both freshwater and seawater throughout their life are particularly interesting model organisms in which we can study the physiological mechanisms by which fishes regulate ion and water homeostasis.

An epithelium is a thin cellular junction that separates compartments within the body, as well as between the body and the external environment. Epithelial cells facilitate important physiological processes such as transport of biomolecules, protection, lubrication, or secretion of fluids. Examples include gas exchange (human lung, amphibian skin, fish gill), nutrient absorption (gastrointestinal tract), hydromineral balance (human kidney, amphibian skin, fish gill, shark rectal gland), protection (mouth, esophagus, and mammalian skin), and lubrication or secretion of fluids (human lung, human sweat and salivary glands). Much of my research has focused on characterizing the molecular mechanisms involved in ion transport across various epithelia. In fishes, ion transport (both absorption and secretion) occurs in the gills, intestine, and kidney and it is vital to maintaining healthy hydromineral balance in freshwater and marine fishes.

An ancient and highly conserved molecular pathway for Cl secretion is found in all Cl secreting epithelia, including the fish gill, elasmobranch rectal gland, reptilian/avian salt gland, and human lung/colon. This pathway for Cl secretion occurs in epithelial cells called “chloride cells” or “ionocytes”. In these Cl secreting ionocytes, Cl is removed from the blood via a basolateral Na+/K+/2Cl cotransporter (NKCC1) and is secreted from the body via an apical Cl channel (cystic fibrosis transmembrane conductance regulator; CFTR); the electrogenic gradient facilitating this Cl transport is produced by the activity of the basolateral Na+/K+/ATPase (NKA). Genetic mutations causing dysfunction of the CFTR have been identified as the disease pathology of Cystic Fibrosis.

Endocrinology of Early Vertebrates

In mammals, aldosterone acts through a mineralocorticoid receptor (MR) to control electrolyte balance and cortisol acts through a glucocorticoid receptor (GR) to control the general stress response. In fishes, aldosterone has no physiological function and cortisol, acting through a GR and an MR, control both osmoregulatory and general stress function. The basal lampreys have neither aldosterone nor cortisol, and a steroid biosynthetic precursor, 11-deoxycortisol, has been implicated as the primary corticosteroid in lamprey controlling the stress response. It is generally accepted that the mineralocorticoid (MR) and glucocorticoid (GR) receptors in later vertebrates descended from a common corticosteroid receptor (CR) found in the agnathans (lamprey and hagfish), but activation of the CR by its corticosteroid ligand(s) is disputed.

Environmental Physiology

Much of my work can be broadly categorized as environmental physiology. I study how animals are adapted to survive changes to their environment, such as from temperature, dissolved gasses (O2, CO2), or salinity, that can occur as a result of tidal, diurnal, and seasonal variation, or as a result of migration between two different environments. In my research, I have worked in the field and in a laboratory setting with aquatic vertebrates (fishes) and invertebrates (crustaceans) to study the organismal, cellular, and molecular mechanisms for thermal tolerance, CO2 tolerance, osmoregulation (ion and water balance), and chemoreception.

Ongoing Projects and Upcoming Manuscripts

Osmoregulation in primitive vertebrates. My doctoral studies at the S.O. Conte Anadromous Fish Research Laboratory (U.S. Geological Survey and University of Massachusetts) were aimed at characterizing molecular mechanisms of osmoregulation in the most basal osmoregulating vertebrate, sea lamprey (Petromyzon marinus). Through this work, I made fascinating discoveries about the nature of basal vertebrate physiology and provided valuable context to physiological studies of more derived vertebrates.

Shaughnessy CA, Barany A, McCormick SD. 2020. 11-Deoxycortisol controls hydromineral balance in the most basal osmoregulating vertebrate, sea lamprey (Petromyzon marinus). [Recently published in Scientific Reports]

Shaughnessy CA, McCormick SD. 2020. Functional characterization and osmoregulatory role of gill Na+/K+/2Cl cotransporter (NKCC1) in sea lamprey (Petromyzon marinus), a basal vertebrate. [Recently published in American Journal of Physiology]

Shaughnessy CA and Breves JP. Molecular mechanisms of Cl transport in fishes: new insights and their evolutionary context [In Press at Journal of Experimental Zoology]

Barany A, Shaughnessy CA, Pelis RM, Fuentes J, Mancera JM, and McCormick SD. Evidence for tissue and salinity-specific Na–Cl cotransporter (NCC)  orthologues involved in ion uptake in the sea lamprey (Petromyzon marinus).

Shaughnessy CA, Daigle A, and McCormick SD. Intrabranchial partitioning of Na+/K+-ATPase activity and osmoregulatory contribution in sea lamprey (Petromyzon marinus) have implications for holobranch evolution.

Shaughnessy CA and McCormick SD. Juvenile sea lamprey (Petromyzon marinus) have a wide window of elevated salinity tolerance that is limited by springtime warming.

Shaughnessy CA, Breves JP, and McCormick SD. An ancient ionocyte: the gills of the marine sea lamprey functionally express anoctamin 1 (Ano1/Tmem16a) and not cystic fibrosis transmembrane conductance regulator (Cftr).

Endocrinology of the sea lamprey. A primary topic of my doctoral dissertation was characterizing the osmoregulatory function of 11-deoxycortisol and its corticosteroid receptor (CR) in lamprey. I also performed studies to better understand the glucose stimulating properties of 11-deoxycortisol in lamprey.

Barany A, Shaughnessy CA, and McCormick SD. Corticosteroid control of Na+/K+-ATPase activity in the intestine of sea lamprey (Petromyzon marinus).

Shaughnessy CA and McCormick SD. Gluconeogenic action of 11-deoxycortisol in sea lamprey (Petromyzon marinus).

Environmental physiology of fishes. In addition to understanding the underlying molecular mechanisms of ion transport, I have a strong affinity for understanding how animals interact with their environment. In this light, I have conducted several studies investigating the physiological response to temperature, CO2, chemical pheremones, and other physiological aspects of migration in animals.

Shaughnessy CA, Balfry SK, Bystriansky JS. Thermal tolerance and heat shock protein response in juvenile sea lamprey (Petromyzon marinus). Growth and osmoregulation of the wolf eel Anarrhichthys ocellatus in dilute salinities.

Shaughnessy CA and McCormick SD. Thermal tolerance and heat shock protein response in juvenile sea lamprey (Petromyzon marinus).

Daigle A, Shaughnessy CA, and McCormick SD. A quantitative re-examination of the classification of the stages of the sea lamprey (Petromyzon marinus) metamorphosis.

Shaughnessy CA, Adren WR, and McCormick SD. Basic amino acid receptor (BAAR) expression in the olfactory rosettes of Atlantic salmon (Salmo salar) during the parr-smolt transformation.

Shaughnessy CA, Kuiste M, Schmid M, Terschak, JA. Avoidance behavior in the invasive European green crab (Carcinus maenas) from the odors of predatory octopuses.