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Georgetown University Medical Center
Departments of Medicine and Physiology & Biophysics |
Kathryn Sandberg, PhD
Professor of Medicine and Physiology
Director, Center for Study of Sex Differences
Suite
232 Building D
4000 Reservoir Rd, NW
Washington, DC 20007
Georgetown University Medical Center
(202) 687-4179; FAX (202) 687-7278
URL:
http://csd.georgetown.edu/sandberg
E-mail:
sandberg@georgetown.edu
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Executive Summary (PDF
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Research Summary |
My
laboratory focuses on the mechanisms underlying sex differences in
disease susceptibility, severity and rate of progression in
hypertension and renal and vascular disease. In collaboration with
Drs. Carmen Hinojosa-Laborde and Christine Maric, we found that 17
- estradiol replacement in the ovariectomized Dahl salt-sensitive rat
attenuated age-induced salt-sensitive hypertension (1) and
glomerulosclerosis and tubulointerstitial damage (6). Moreover, these
studies suggest that 17 -
estradiol-mediated reductions in angiotensin type 1 receptor (AT R)
densities in the kidney and adrenal contribute to the attenuation in
blood pressure and associated renal injury observed in the estrogen
replete female. In collaboration with Dr. Carlo Pesce, we found that
17 - estradiol attenuated
indices of renal damage as well in the renal wrap (RW) model of
hypertension (2). Our recent research indicates that 17
- estradiol-mediates renal protection in RW hypertension by reducing
renal levels of reactive oxygen species through attenuating ATR-mediated
activation of renal cortical NAD(P)H oxidase activity. Taken together,
these studies suggest that sex differences in gonadal steroid
regulation of the ATR
contribute to the differences in male and female susceptibility to
hypertension and renal disease progression.
My lab is also interested in the molecular mechanisms underlying ATR
regulation. In collaboration with Dr. Darren Roesch, we found that 17
- estradiol attenuates ATR-mediated
aldosterone release by inhibiting translation of the adrenal cortical
ATR (8).
Furthermore, ATR
translation was found to be regulated by RNA binding proteins that
interact with a hairpin loop within exon 2 of the ATR
5’ leader sequence (3). Two upstream AUGs in exon 2 were shown to
mediate exon 2 repression of translation and alternative splicing of
exon 2 was shown to contribute to tissue-specific expression of the ATR
(9). In collaboration with Drs. Susan Mulroney and Christine Maric, we
have also found that translational control of ATRs
contributes to the regulation of ATR
density by: 17 - estradiol in
the adrenal cortex (8); osmolality in the renal medulla (5);
uninephrectomy in the renal cortex (7); and, proliferation in vascular
smooth cells (4). |
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| Selected Publications |
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1. Hinojosa-Laborde C, Craig T,
Zheng W, Ji H, Haywood JR, and Sandberg K.
Ovariectomy
augments hypertension in aging female Dahl salt-sensitive rats.
Hypertension 44: 405-409, 2004.
2. Ji H, Menini S, Mok K, Zheng W,
Pesce C, Kim J, Mulroney S, and Sandberg K.
Gonadal
steroid regulation of renal injury in renal wrap hypertension.
Am J Physiol Renal Physiol 288: F513-520, 2005.
3. Ji H, Zhang Y, Zheng W, Wu Z,
Lee S, and Sandberg K.
Translational
regulation of angiotensin type 1a receptor expression and signaling by
upstream AUGs in the 5’ leader sequence.
J Biol Chem 279: 45322-45328, 2004.
4. Lee S, Ji H, Wu Z, Zheng W,
Hassan A, and Sandberg K.
Translational regulation of angiotensin II type 1
receptors in proliferating vascular smooth muscle cells.
Am J Physiol: Regul
and add reference 290: R50-56, 2006.
5. Lee S, Wu Z, Sandberg K, Yoo SE,
and Maric C.
Posttranscriptional mechanisms contribute to osmotic
regulation of angiotensin type 1 receptors in cultured rat renomedullary
interstitial cells.
Am J Physiol: Regul 290: R44-49, 2006.
6. Maric C, Sandberg K, and
Hinojosa-Laborde C.
Glomerulosclerosis
and tubulointerstitial fibrosis are attenuated with 17-estradiol in the aging
Dahl salt sensitive rat.
J Am Soc Nephrol 15: 1546-1556, 2004.
7.
Mok KY, Sandberg K, Sweeny JM,
Zheng W, Lee S, and Mulroney SE.
Growth hormone regulation of glomerular AT1 angiotensin
receptors in adult uninephrectomized male rats.
Am J Physiol: Regul Integr Comp Physiol
285: F1085-1091, 2003.
8. Wu Z, Maric C, Roesch DM, Zheng
W, Verbalis JG, and Sandberg K.
Estrogen
regulates adrenal angiotensin AT1 receptors by modulating AT1
receptor translation.
Endocrinology 144: 3251-3261, 2003.
9.
Zhang, Y., Ji, H., Zheng, W., Falconetti, C., Fabucci, M.E., and K. Sandberg,
Translational control of the rat angiotensin
type 1a receptor by alternative
splicing.
Gene 341: 93-100, 2004. |
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Kathryn Sandberg, PhD