Epithelial ion transport
An epithelium is a thin junction, sometimes the width of only a single cell, that separates compartments within the body, as well as between the body and the external environment. Epithelia facilitate important physiological processes such as transport of biomolecules, protection, lubicration, 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 and it is vital to maintaining healthy hydromineral balance in freshwater and marine fishes. In humans, ion reabsorption in the kidney is critical to maintaining proper hydromineral balance. In the human lung and intestine, chloride ion secretion is critical to maintaining proper moisture and mucociliary clearance of these epithelia and avoiding an over-abundance of mucus harboring unhealthy bacteria.
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 this 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.
Past and current projects on epithelial ion transport
- Molecular mechanisms of branchial Cl– secretion in sea lamprey (Petromyzon marinus)
- Intestinal ion and water balance in sea lamprey (Petromyzon marinus)
- Kinetics studies on the Na+/K+-ATPase (NKA) in sturgeon (Acipenser transmontanus) and salmon (Salmo salar)
- Interaction of branchial ion and acid-base transport in the sturgeon (Acipenser transmontanus)
Much of my work can be summarized 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.
One topic of environmental physiology 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.
Past and current projects in environmental physiology
- Characterizing the development and maintenance of seawater tolerance in sea lamprey (Petromyzon marinus) throughout Springtime warming
- Thermal tolerance studies on trout (Salvelinus fontinalis), herring (Alosa sapidissima), and sea lamprey (Petromyzon marinus)
- Interaction of salinity and pH tolerance in estuarine purple marsh crab (Sesarma reticulatum)
- Olfaction and imprinting in salmon (Salmo salar)
- Chemoreception and chemical-mediated predator avoidance behavior in the invasive European green crab (Carcinus maenus)
As you can read below, my research interests can be more specifically characterized as studying (i) the molecular processes of ion transport and (ii) the endocrine signaling pathways controlling ionoregulatory and stress physiology.
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. A primary topic of my doctoral dissertation has been characterizing the osmoregulatory function of 11-deoxycortisol and its corticosteroid receptor (CR) in lamprey.
Past and current projects in comparative endocrinology
- Corticosteroid control of osmoregulation in sea lamprey (Petromyzon marinus)
- Role of cortisol in seawater acclimation in brook trout (Salvelinus fontinalis)
- Gluconeogenic action of corticosteroids in basal vertebrates
- Receptor dynamics in mediating corticosteroid signaling