Research

Faculty

Diana W. Bianchi, MD
Cheryl L. Garganta, MD, PhD
Mark S. Korson, MD

Diana W. Bianchi, MD
Vice Chair for Research, Floating Hospital for Children
Natalie V. Zucker Professor of Pediatrics, Obstetrics, and Gynecology

Genetics/Metabolism
Tel: 617-636-1468

Education/Training

University of Pennsylvania, Philadelphia, PA	BA	1976	Biology
Stanford University School of Medicine	MD	1980	Medicine
Children's Hospital, Boston, MA		1980-83	Residency in Pediatrics
Joint Program in Neonatology, Harvard Medical School		1983-86	Postdoctoral Fellowship in Neonatology
Children's Hospital, Boston, MA		1983-86	Postdoctoral Fellowship in Medical Genetics

Research Interests

Dr. Bianchi’s laboratory group focuses on four areas:

(1) the isolation of intact fetal cells from maternal blood as a non-invasive test for aneuploidy
(2) fetomaternal and maternofetal nucleic acid trafficking
(3) fetal cells in the mother post-partum and their association with immune disorders
(4) fetal cells in the mother as an alternative source of therapeutic stem cells.

Her group was the first to demonstrate that fetal nucleated erythrocytes are an excellent target cell to isolate from maternal blood. She has had a number of publications that focus on basic biological differences between fetal blood cells and immature maternal cells. She has been a principal investigator or co-principal investigator in 2 large obstetric clinical trials: the NIFTY (National Institute of Health Fetal Cell Study) trial and the FASTER (First and Second Trimester Evaluation of Risk for Aneuploidy) trial. The NIFTY trial’s focus was the comparison of fetal aneuploidy detection by maternal blood sampling with the “gold standard” of prenatal diagnosis, metaphase chromosome analysis from cells obtained from an invasive procedure, such as amniocentesis or CVS.

More recently, Dr. Bianchi’s group has studied cell-free fetal DNA in maternal plasma and serum, and its association with abnormalities of pregnancy. Her group has shown that when the fetus has trisomy 21, there is twice the amount of fetal DNA present compared with euploid fetuses. Her group has also been the first to demonstrate that there are large amounts of cell-free fetal DNA and mRNA in the amniotic fluid. This observation presents a novel opportunity for clinical correlation and gene expression studies. This work is currently funded by NICHD.

Dr. Bianchi’s group was also the first to demonstrate that fetal cells can persist in the mother for as long as 27 years following the delivery of the infant. This finding has led to the development of the field of fetal cell microchimerism. Fetal cells have now been shown to be associated with a number of autoimmune diseases that are more prevalent in women compared with men, such as scleroderma, lupus, and autoimmune thyroiditis. Using fluorescence in situ hybridization (FISH) techniques her group has also recently demonstrated that fetal cells can develop into mature thyroid and liver tissue in the mother. These remarkable findings imply that fetal cells, presumably transfused as a result of pregnancy and delivery, can serve as a secondary source of stem cells, with potential for differentiation into a variety of tissues. This work is also currently funded by NICHD.

Key Publications

Fetal Cell Microchimerism/Fetal Stem Cells

Bianchi, D.W., Zickwolf, G.K., Weil, G.J., Sylvester, S., DeMaria, M.A. Male fetal lymphoid progenitor cells persist in maternal blood for as long as 27 years post-partum. Proc Natl Acad Sci USA, 93: 705-708 (1996).

Nelson J.L., Furst D.E., Maloney S., Gooley T., Evans P., Smith A., Bean M.A., Ober C., Bianchi D.W. Microchimerism and HLA-compatible relationships of pregnancy, and scleroderma. Lancet 351:559-562 (1998).

Johnson KL, Nelson JL, Furst DE, McSweeny P, Zhen DK, Bianchi D.W. Fetal cell microchimerism in tissues from multiple sites in women with systemic sclerosis. Arthritis Rheum 44:1848-1854 (2001).

Srivatsa B, Srivatsa S, Samura O, Johnson KL, Lee SL, Bianchi D.W. Microchimerism of presumed fetal origin in thyroid specimens from women: a case-control study. Lancet 358:2034-2038 (2001).

Johnson KL, Samura O, Nelson JL, McDonnell WM, Bianchi D.W. Significant fetal cell microchimerism in a nontransfused woman with hepatitis C: Evidence of long-term survival and expansion. Hepatology 36:1295-1297 (2002).

Srivasta B, Srivatsa S, Johnson KL, Bianchi D.W. Maternal cell microchimerism in newborn tissues. J Pediatr 142 31-35 (2003).

Khosrotehrani K, Johnson KL, Lau J, Dupuy A, Cha DH, Bianchi D.W. The influence of fetal loss on the presence of fetal cell microchimerism: a systematic review. Arthritis Rheumatism 2003; 48:3237-3241.

Khosrotehrani K, Johnson KL, Cha DH, Salomon R, Bianchi D.W. Pregnancy-associated fetal progenitor/stem cells (PAPCs) differentiate into epithelial cells and hepatocytes in maternal organs. JAMA 2004; 292:75-80.

Khosrotehrani K, Bianchi D.W. Multi-lineage potential of fetal cells in maternal tissue: a reverse legacy. J Cell Sci 2005; 118:1559-1563.

Fetomaternal Trafficking of Cell-Free Nucleic Acids

Bianchi D.W., Lo YMD. Fetomaternal cellular and plasma DNA trafficking: The yin and the yang. NY Acad Sci 945:119-131(2001).

Bianchi D.W., LeShane ES, Cowan JM. Large amounts of cell-free fetal DNA are present in amniotic fluid. Clin Chem 47:1867-1869 (2001).

Lee T, LeShane ES, Messerlian GM, Canick JA, Farina A, Heber WW, Bianchi D.W. Down syndrome and cell-free fetal DNA in archived maternal serum. Am J Obstet Gynecol 187:1217-1221 (2002).

Levine RJ, Qian C, LeShane ES, Yu K, England L, Schisterman E, Wataganara T, Romero R, Bianchi D.W. Two stage elevation of cell-free fetal DNA in maternal sera before onset of preeclampsia. Am J Obstet Gynecol 2004; 190:707-713.

Larrabee PB, Johnson KL, Pestova E, Lucas M, Wilber K, LeShane ES, Tantravahi U, Cowan JM, Bianchi D.W. Microarray analysis of cell-free fetal DNA in amniotic fluid: a prenatal molecular karyotype. Am J Hum Genet 2004;75:485-491.

Larrabee PB, Johnson KL, Lai C, Ordovas J, Cowan JM, Tantravahi U, Bianchi D.W. Global gene expression analysis in the living human fetus using amniotic fluid: a feasibility study. JAMA 2005; 293: 836-842.

Fetal Cells In Maternal Blood

Bianchi, D.W., Flint, A.F., Pizzimenti, M.F., Knoll, J.H.M., Latt, S.A. Isolation of fetal DNA from nucleated erythrocytes in maternal blood. Proc Natl Acad Sci USA 87: 3279-3283 (1990).

Bianchi D.W., Williams J.M., Sullivan L.M., Hanson F.W., Klinger K.W., Shuber A.P. PCR quantitation of fetal cells in maternal blood in normal and aneuploid pregnancies. Am J Hum Genet 61:822-829 (1997).

Bianchi D.W., Simpson JL, Jackson LG, and the NIFTY study group. Fetal gender and aneuploidy detection using fetal cells from maternal blood: Analysis of NIFTY I data. Prenat Diagn 22:609-615 (2002).

Cheryl L. Garganta, MD, PhD
Assistant Professor of Pediatrics, Genetics/Metabolism

Education/Training

Wheaton College, Norton, MA	BA	1978-81	Chemistry
Medical College of Virginia, Richmond, VA	MS	1981-83	Biochemistry
Medical College of Virginia, Richmond, VA	MD	1985-87; 1989-91	Medicine
Medical College of Virginia, Richmond, VA	PhD	1987-89; 1994-95	Human Genetics
Medical College of Virginia, Virginia Commonwealth University Richmond, VA	Internship / Residency	1991-1994	Pediatrics
Yale University Richmond, VA	Residency	1998-2001	Clinical and Biomedical Genetics

Research Interests

As a biochemical geneticist, Dr. Garganta is interested in measuring small molecules in human blood and body fluid for the diagnosis and management of metabolic disease. In her lab, she is starting to apply this to mitochondrial disorders where diagnostic testing requires invasive procedures and cannot be used to determine treatment effectiveness.

Key Publications

Bolteus AJ, Garganta C, Bordey A. Assays for measuring extracellular GABA levels and cell migration rate in acute slices. Brain Research Protocols 14(2005)126-134.

Garganta CL and Czyzyk DJ. Separation and quantification of branched chain amino acids by LC/MS/MS. American Journal of Human Genetics 75(2004)supp.

Williamson A, Garganta CL, Petroff OA. Disruptions in glutamate-glutamine cycling alter GABA function.  Epilepsia 45(2004) supp 7:360.

Mudd SH, Braverman N, Pomper M, Tezcan K, Kronick J, Jayakar P, Garganta C, Ampola MG, Levy HL, McCandless SE, Wiltse H, Stabler SP, Allen RH, Wagner C, Borschel MW. Infantile hypermethioninemia and hyperhomocysteinemia due to high methionine intake: a diagnostic trap. Molecular Genetics and Metabolism 79 (2003)6-16.

Mark S. Korson, MD
Associate Professor of Pediatrics, Genetics/Metabolism

Education/Training

University of Toronto, Toronto, Canada		1976-78	General Science
University of Toronto, Toronto, Canada	MD	1978-82	Medicine
St. Joseph's Health Center, Toronto, Canada	Rotating Internship	1982-93
The Hospital for Sick Children, Toronto, Canada	Residency	1983-86	Pediatrics
Children's Hospital, Boston, MA		1986-90	Clinical and Biochemical Genetics

Research Interests

1. Exploration of the clinical, biochemical and molecular aspects of the inborn errors of metabolism
2. Evaluation of the natural evolution of metabolic disease in adults
3. Development of better mechanisms for community health care maintenance for patients with inborn errors of metabolism, especially over large distances
4. Development of teaching methods for training physicians, residents and medical students about genetic metabolic disorders.

Key Publications

North KN, Shoffner JM, Korson M, Holm I. Oxidative phosphorylation defect associated with primary adrenal insufficiency. J Pediatr 1996;128:688-92.

Schwartz ML, Cox GF, Lin AE, Korson MS, Perez-Atayde A, Lacro RV, Lipshultz SE. Clinical approach to genetic cardiomyopathy in children. Circulation 1996;94:2021-38.

Marin-Garcia J, Anantharishnan R, Korson M, Goldenthal MJ, Perez-Atayde A. Cardiac mitochondrial dysfunction in Leigh syndrome. Pediatr Cardiol 1996:17:387-9.

Casta A, Quackenbush EJ, Houck CS, Korson MS. Perioperative white matter degeneration and death in a patient with a defect in mitochondrial oxidative phosphorylation. Anesthesia 1997;87(2):420-5.

Cox GF, Souri M, Aoyama T, Rockenmacher S, Varvogli L, Rohr F, Hashimoto T, Korson MS. Reversal of severe hypertrophic cardiomyopathy and excellent neuropsychologic outcome in very-long-chain acyl-coenzyme A dehydrogenase deficiency. J Pediatr 1998;133:247-53.

Smith KL, Bradley L, Levy HL, Korson MS. Inadequate laboratory technique for amino acid analysis resulting in missed diagnoses of homocystinuria. Letter to the Editor, Clin Chem 1998;44(4):897-8.

Masek BJ, Sims K, Bove C, Korson MS, Short P, Norman D. Quality of life assessment in adults with type I Gaucher disease. Quality Life Res 1999:8(3):263-8.

Prasad C, Nurko S, Borovoy J, Korson M. The importance of gut motility in the metabolic control of propionic acidemia. J Pediatr 2004;144(4):532-35.

Hill KP, Lukonis CJ, Korson MS, Weinstein C, Thall M, Schwartz JT. Neuropsychiatric illness in a patient with cobalamin G disease, an inherited disorder of vitamin B12 metabolism. Harvard Rev Psychiatr 2004;12(2):116-22.  

Allard P, Cowell LD, Zytkovicz TH, Korson MS, Ampola MG. Determination of phylalanine and tyrosine in dried blood specimens by ion-exchange chromatography using the Hitachi L-8800 analyzer.  Clin Biochem 2004;37(10):857-62.

Allard P, Grenier A, Korson MS, Zytkovicz TH. Newborn screening for hepatorenal tyrosinemia by tandem mass spectrometry: Analysis of succinylacetone extracted from dried blood spots.  Clin Biochem 2004;37:1010-5.

Chandler RJ, Tsai MS, Dorko K, Sloan J, Korson M, Freeman R, Strong S, Venditti CP. Adenoviral-mediated correction of methylmalonyl-CoA mutase deficiency in murine fibroblasts and human haptocytes. BMC Med Genet. 2007;8:24-34.