Fred Lamb, M.D., Ph.D. (Full Member)
Professor, Dept. of Pediatrics, University of Iowa

http://www.uihealthcare.com/depts/med/pediatrics/pedsmds/lamb.html

Research Interest    

Dr. Lamb's research focuses on the biophysical properties and function of ClC-3, a member of the ClC family of chloride ion transporters. The laboratory's primary emphasis has been on understanding the function of ClC-3 in vascular smooth muscle cells, but his research on the biology of ClC-3 and other related ClC channels is relevant to CF research efforts in the Center. Alternative pathways of Cl- transport are potentially important modifiers of cystic fibrosis lung disease. While characterizing the ontogeny of the expression of CLC chloride channels in human lung tissues, they have demonstrated that CLCN3 is the most highly expressed ClC channel in the developing human lung. More recently, the Lamb group has been studying the role of ClC-3 in proinflammatory signaling pathways controlled by NADPH oxidase (Nox)-dependent reactive oxygen species. This work suggests that ClC-3 functions as a Cl-/H+ antiporter, and that it may provide charge neutralization required for the production of superoxides by Nox1 and Nox2 at the level of the endosome. Using a ClC-3 knockout mouse model, they have demonstrated that in the absence of ClC-3, NFkB signaling by reactive oxygen species in response to TNFalpha, IL-1beta and endotoxin is disrupted.

Selected Publications:

Miller FJ Jr., Filali MS, Huss GJ, Stanic B, Chamseddine A, Barna TJ, and FS Lamb. Cytokine activation of NF-kappaB in vascular smooth muscle cells requires signaling endosomes containing Nox1 and ClC-3. Circulation Research, 101:663-671, 2007.

Itani OA, Lamb FS, Melvin JE and MJ Welsh. Basolateral chloride current in human airway epithelia. Am. J. Physiol. Lung 293: L991-999, 2007.

Moreland, JG, Davis AP, Matsuda JJ, Hook JS, Bailey G, Nauseef WM, and FS Lamb. Endotoxin priming of neutrophils requires NADPH-oxidase generated oxidants and is regulated by the anion transporter ClC-3. Journal of Biological Chemistry 282:33958-67, 2007.

Matsuda JJ, Filali M, Volk, KA, Collins M, Moreland JG and FS Lamb. ClC-3 currents in HEK293 cells are pH-dependent. Am. J. Physiol. 294:C251-62, 2008.

Publications from PubMed