Dan R. Halm, Ph.D. Associate Professor Address: 063 Medical Sciences Building Phone: (937) 775-2742 E-mail: dan.halm@wright.edu University of Iowa, 1981

Research Interests:

Epithelial Physiology

Epithelial tissues form the barrier between the body interior and the external environment. Cells making up epithelia support fluid and electrolyte balance, absorption of nutrients and excretion of waste products, as well as contributing to the immune defense system. Current research in this lab focuses on the regulation of membrane transport processes responsible for secretion of CI-, K+ and H+ in the intestinal epithelium. In part, stimulation of these ion secretory pathways requires the insertion, into the plasma membrane, of ion channels residing in the membrane of secretory granules. During these exocytotic events, granule contents (primarily mucous molecules) are released into the intestinal lumen. Monitoring cellular events in epithelia is accomplished using optical and electrical recording techniques. Ion channels involved in secretion are detected with the patch-clamp technique, which is sensitive to these small electrical currents. Fluorescent dyes are non-invasively loaded into epithelial cells to follow selective changes in ion composition, in particular, cell pH, Ca++ and CI-. Operations of specific ion transporters are inferred from changes in cellular concentration during stimulation with secretagogues or changes in bathing solution composition. Morphological features of epithelial cells, such as granule exocytosis, are imaged with high resolution optics. From these studies, coordination of individual steps in the process of secretion can be delineated. Clinically, the inappropriate operation of these cellular functions contributes to inflammatory bowel disease and secretory diarrheas; greater knowledge of the interrelations between immune defenses and fluid balance could lead to therapeutic solutions to these disorders. 

Selected Publications:

Liao T, Wang L, Halm ST, Lu L, Fyffe REW, Halm DR (2005) The K⁺ channel KvLQT (Kcnq1) located in the basolateral membrane of distal colonic epithelium is not essential for activating Cl secretion. Am J Physiol, Cell Physiol 289:C564-C575.

Halm DR (2004) Secretory control of basolaterial membraine K⁺ and Cl^- channels in colonic crypt cells. In: Cell volume and signaling, Vol. 559, Advances in experimental medicine and biology (Lauf PK, Adragna NC, eds), pp 119-129. New York: Springer.

Li Y, Halm ST, Halm DR (2003) Secretory activation of basolateral membrane Cl^- channels in guinea pig distal colonic crypts. Am J Physiol, Cell Physiol. 284:C918-C933.

Michail SK, Halm DR, Abernathy F (2003) Enteropathogenic Escherichia coli: Stimulating neutrophil migration across a cultured intestinal epithelium without altering transepithelial conductance. J Ped Gastroenterol Nutr 36:253-260.

Li Y, Halm DR (2002) Secretory modulation of basolateral membrane inwardly rectified K⁺ channel in guinea pig distal colonic crypts. Am J Physiol, Cell Physiol 282:C719-C735.

Halm DR, Halm ST (2001)  Prostanoids stimulate K⁺ and Cl^- secretion in guinea pig distal colon via distinct pathways. Am J Physiol Gastrointest Live Physiol 281:G984-G996.

Halm DR, Halm ST (1999) Secretagogue response of goblet cells and columnar cells in human colonic crypts. Am J Physiol, Cell Physiol 277:C501-C522; corrigenda 278:C212-C233.

Halm, DR (1998) Identifying swelling-activated channels from ion selectivity patterns. J Gen Physiol 112:369-371.

Rechkemmer GR, Frizzell RA, Halm DR (1996) Active K+ transport across guinea pig distal colon: Action of secretagogues. J Physiol 493:485-502.

Halm DR, Halm ST, DiBona DR, Frizzell RA, Johnson RD (1995) Selective stimulation of epithelial cells in colonic crypts: relation to active Cl^- secretion. Am J Physiol, Cell Physiol 269:C929-C942.

Halm DR, Halm ST (1994) Aldosterone stimulates K+ secretion prior to onset of Na⁺ absorption in guinea pig distal colon. Am J Physiol, Cell Physiol 266:C552-C558.