Fred S. Lamb, MD, PhD
Research Profile
Research Interests:
- Vascular smooth muscle physiology and biophysics, including electrophysiologic
mechanisms of contraction and relaxation and blood vessel reactivity
in pathologic states.
- Molecular biology and molecular genetics of ClC-3 chloride ion channels.
- Fetal programming of adult vascular disease.
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Lab Members:
- Mohammed Filali PhD Assistant Research Scientist.
- Thomas Barna, Research Assistant III
- Gilbert Aldape MD Research Assistant I
There are also 3 undergraduate students working in the lab.
Affiliations:
Model System:
Our primary model system is a ClC-3 chloride channel knockout mouse
that we developed. We perform both in vivo and in vitro studies. A major
focus is in vitro assessment of both large and small blood vessel function
including wire myography and videomicroscopy. From this knockout animal
we have also derived cultured vascular smooth muscle cells that are used
for a variety of experiments including patch-clamp recording of ion currents
and fluorescent quantification of free radical metabolism.
Our second experimental system is a sheep model of fetal programming.
Pregnant ewes are given 2 days of dexamethasone infusion in the first
trimester. Steroid-exposed lambs develop hypertension and abnormalities
in coronary artery function. These studies are undertaken in collaboration
with Dr. Segar and Dr. Scholz. We are studying multiple aspects of altered
vascular physiology and biology in this model.
Recent Publications:
- Arreola, J, Begenisich T, Nehrke K, Nguyen H-V, Park K, Richardson
L, Yang B, Schutte BC, Lamb FS and Melvin JE. Secretion and cell
volume regulation by salivary acinar cells from mice lacking expression
of the Clcn3 Cl- channel gene. J Physiol (Lond) 545: 207–216,
2002.
- Dickerson LW, Bonthius DJ, Schutte BC, Yang B, Barna TJ, Carter
MC, Nehrke K, Williamson RA and Lamb FS. Altered GABAergic function
accompanies hippocampal degeneration in mice lacking ClC-3 voltage-gated
chloride channels. Brain Res 958: 227-250, 2002.
- Roghair RD, Lamb FS, Bedell KA, Smith OM, Scholz TD and JL Segar.
Late gestation betamethesone upregulates coronary artery responsiveness
to angiotensin II in fetal sheep. Am. J. Physiol. 286:R80-88, 2004.
- Robinson NC, Huang P, Kaetzel MA, Lamb FS and DJ Nelson. Identification
of an N-terminal amino acid of CLC-3 critical in phosphorylation-dependent
activation of IClCaMKII. J. Physiol. (Lond.), 556:353-68, 2004.
- Yamamoto-Mizuma S, Wang G-X, Liu LL, Schegg K, Hatton WJ, Duan
D, Horowitz B, Lamb FS, and JR Hume. Altered properties of volume-sensitive
osmolyte and anion channels (VSOACs) and membrane protein expression
in cardiac and smooth muscle myocytes from Clcn3(-/-) mice. J. Physiol.
(Lond.) 557:439-56, 2004.
- Bartlett HL, Scholz TD, Lamb FS and DL. Weeks. Characterization
of embryonic cardiac pacemaker and atrioventricular conduction physiology
in Xenopus laevis using non-invasive imaging. Am. J. Physiol. 286:H2035-41,
2004.
- Roghair RD, Lamb FS, Miller FJ Scholz TJ and JL Segar. Early gestation
dexamethasone programs enhanced postnatal ovine coronary artery vascular
reactivity. In Press, Am. J. Physiol. Regulatory, Integrative and
Comparative Physiology, 2004.
- Lazartigues E, Lawrence AJ, Lamb FS and RL Davisson. Renovascular
Hypertension in Mice with Brain-Selective Overexpression of AT1a
Receptors is Buffered by Increased Nitric Oxide Production in the
Periphery. Circ. Res. 95:523-31, 2004.
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