George J. Schwartz, M.D.

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Dr. Schwartz' research interests are:

1) Molecular physiology of acid-base disturbances

2) Kidney tubular acidosis

3) Disorders of sodium, potassium, and magnesium transport

4) Carbonic anhydrase deficiency diseases

5) Assessment of kidney function (glomerular filtration rate)

The long term goal is to determine how intercalated cells of the kidney cortical collecting duct (CCD) sense a change in extracellular pH and adapt by reversing their polarity of H+/HCO3 transporters. After exposure to a 3 h incubation at pH 6.8, rabbit CCDs, which normally secrete HCO3, reverse polarity, secrete H+ and endocytically remove apical Cl/HCO3 exchangers to stop HCO3 secretion. The novel protein hensin is expressed in the extracellular matrix (ECM) surrounding adapting HCO3-secreting intercalated cells (B-ICs) and plays a key role in this adaptation.

Aim 1 determines the mechanisms by which polymerized hensin is deposited in the ECM and how hensin signals the adaptation of B-ICs during metabolic acidosis. Other proteins interacting with hensin include integrins, galectin 3, and cyclophilin A (cyp A); these proteins may be regulated by acid-base disturbances and hensin polymerization. Cyclosporin (CsA) causes renal tubular acidosis and inhibits cyp A peptidyl prolyl isomerase activity. To assess CsA's effect, cultured intercalated cells are plated at high density in the presence of CsA and examined for hensin polymerization in the media and ECM. A cyp A "knockdown" model using siRNAs will be examined similarly; to determine if hensin fails to polymerize without this isomerase activity.

Aim 2 examines the adaptation of CCD ICs to metabolic alkalosis regarding proteins of the hensin pathway and investigates if in vitro alkalosis can reverse the adaptation occurring in response to in vivo metabolic acidosis.

Aim 3 addresses early events in response to metabolic acidosis. Our data suggest that low cell pH is the signal to initiate the adaptation; the role of the adjacent principal cell in this signaling will be determined. We will show whether low pH stimulates endothelin-1 and nitric oxide, and whether they mediate changes in HCO3 transport during acidosis. The early steps of tyrosine phosphorylation and c-Src activation in response to low pH will also be examined.

These studies will illustrate how ICs respond to acid-base perturbations and change functional polarity.

Specialty

Nephrology

Current Appointments

• Professor - Department of Pediatrics (SMD)

Education
MD Medicine	Case Western Reserve University School of Medicine	1972
AB Chemistry	Colgate University	1968

Post-Doctoral Training & Residency
Senior Staff Fellow, National Heart, Lung and Blood Institute, Laboratory of Kidney and Electrolyte Metabolism	1978 - 1979
Guest Worker, National Heart, Lung and Blood Institute, Laboratory of Kidney and Electrolyte Metabolism	1976 - 1978
Pediatric Nephrology Fellowship, Albert Einstein College of Medicine, Bronx, NY	1974 - 1976
Residency in Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA	1972 - 1974

Fellowship Awards
NIH F32 Post-doctoral fellowship award, GJ Schwartz	1977 - 1978
Post-doctoral NIH NRSA trainee in Pediatric Nephrology; Adrian Spitzer, MD, Principal Investigator.	1974 - 1976

Board Certifications
American Board of Pediatrics, Pediatric Nephrology	1979 - Present
American Board of Pediatrics	1977 - Present

Recent Journal Articles
Showing the 5 most recent journal articles. (103 available)
Lande, MB.; Adams, H.; Falkner, B.; Waldstein, SR.; Schwartz, GJ.; Szilagyi, PG.; Hongyue, W.; Palumbo, D. "Parental Assessments of Intenalizing and Extenalizing Behavior and Executive Function in Children with Primary Hypertension." Journal of Pediatrics 154 (2009): 207-212.
Schwartz, GJ.; Muñoz, A.; Schneider, MF.; Mak, RH.; Kaskel, F.; Warady, B.; Furth. "New Equations to Estimate GFR in Children with CKD." J. Am. Soc. Nephrol 20 (2009): 629-637.
Wong, CS.; Pierce, CB.; Cole, SR.; Warady, B.; Mak, R.; Kaskel, R.;Furth, S.; Schwartz, GJ. "Association of proteinuria with race, cause of chronic kidney disease, and glomerular fitration rate in the chronic kidney disease in children study." Clin J Am Soc Nephrol 4 (2009): 812-819.
Peng, H.; Vijayakumar, S.; Schiene-Fischer, C.; Li, H.; Purkerson, JM.; Malesevic, M; Liebscher, J.; Al-Awqati, Q.; Schwartz, GJ. "Secreted Cyclophilin A, A peptidyl prolyl cis/trans isomerase, mediates matrix assembly of hensin, a protein implicated epithelial differentiation." J Biol Chem 284 (2009): 6465-6475.
Schwartz, GJ.; Kwong, T.; Erway, B.; Warady, B.; Sokoll, L.; Hellerstein, S.; Dharnidarka, V.; Furth, S.; Munoz, A. "Validation of creatinine assays utilizing HPLC and IDMS traceable standards in Sera of children." Pediatr Nephrol (2009): 113-9.