Margaret A. Keller, Ph.D., is an Associate Professor at Coriell Institute (CIMR) and principal investigator on the New Jersey Stem Cell Resource. This important state-funded resource was established in 2005 to distribute stem cells derived from umbilical cord blood and placental waste material to researchers in the state and worldwide. These materials are obtained from the New Jersey Cord Blood Bank (NJCBB), located at CIMR; specifically, stem cells are derived from donations that are insufficient in volume to be used for bone marrow transplantation, the mission of the NJCBB. These stem cells include those expressing the CD34 surface antigen, a hallmark of stem cells with potential to differentiate into hematopoietic cells, as well as multipotent mesenchymal stromal cells which contain a subpopulation of mesenchymal stem cells with the potential to differentiate into osteoblasts, adipocytes and chondroblasts. Access to such reagents is critical to many areas of biomedical research including research aimed at understanding normal cell development, cancer and other disease processes. Dr. Keller is also involved in the management of the Coriell Cell Repositories (CCR) and National Institute of Neurological Disorders and Stroke (NINDS) Human Genetics Resource Center, which is committed to distributing well-characterized cell and DNA samples from individuals with neurological disorders to researchers for use in genetic association studies.
Dr. Keller obtained her doctoral degree in 1994 in molecular genetics at the University of Pennsylvania (UPenn) and completed a post-doctoral fellowship at DuPont Merck Pharmaceutical Company in Wilmington, Delaware. She then took the position of Administrative Director of The Nucleic Acid and Protein Core Facility at The Children’s Hospital of Philadelphia (CHOP), which performs genomic and protein analyses for CHOP and UPenn researchers. In 1996, Dr. Keller joined the hematology research group at A.I. duPont Hospital for Children in Wilmington, Delaware where she was awarded one of ten Scholar’s Awards supported by the NIH-funded Cooperative Sickle Cell Centers. In 2001 she joined the faculty of the Department of Medicine in Jefferson Medical College at Thomas Jefferson University in Philadelphia. At Jefferson, Dr. Keller also directed DNA-based screening for inherited thrombophilia performed by the Cardeza Special Hemostasis and Hematology Laboratory. Dr. Keller joined the faculty of the Coriell Institute in 2006.
Dr. Keller has examined the regulation of expression of a family of low affinity receptors for IgG as well as determined the molecular defect responsible for inherited hematologic disorders including hemoglobinopathies and hypodysfibrinogenemia. She has conducted a small-scale candidate gene association study in sickle cell disease (SCD) demonstrating that a polymorphism located in the promoter region of the endothelial nitric oxide synthase gene (eNOS) is associated with a history of acute chest syndrome in females with SCD. Most recently, Dr. Keller’s research interests have been focused in two areas: 1) deciphering the repertoire of transcriptional regulators critical for committing the hematopoietic progenitor cell to the red cell lineage, and 2) identifying agents that alter the regulation of hemoglobin expression as a potential therapeutic strategy for treatment of sickle cell disease and b thalassemia. Cord blood- and adult peripheral blood-derived CD34+ cells can be cultured in the laboratory under conditions that foster erythroid differentiation. The erythroid progenitor cells generated in this way can be examined using functional genomic and computational biology approaches. Currently, Dr. Keller is interested in the epigenetic regulation of hematopoeitic progenitor cells and, in collaboration with researchers at Thomas Jefferson University, is using chromatin immunoprecipitation analysis to examine histone occupancy of transcriptional regulatory elements of the globin genes.
Peer-reviewed Articles
Gwinn K, Corriveau RA, Mitsumoto H, Bednarz K, Brown RH, Cudkowicz M, Gordon PH, Hardy J, Kasarskis EJ, Kaufmann P, Miller R, Sorenson E, Tandan R, Traynor BJ, Nash J, Sherman A, Mailman MD, Ostell J, Bruijn L, Cwik V, Rich SS, Singleton A, Refolo L, Andrews J, Zhang R, Conwit R, Keller MA; for The ALS Research Group.
Amyotrophic Lateral Sclerosis: An Emerging Era of Collaborative Gene Discovery
PMID: 18060051 PubMed - in process
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Keller, M.A., Addya, S., Vadigepalli, R., Banini, B., Delgrosso, K. and S. Surrey
Transcriptional regulatory network analysis of developing human erythroid progenitors reveals patterns of co-regulation and potential transcriptional regulators.
Physiological Genomics (in press).
PMID: 16940433 abstract
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Keller MA, Martinez J, Baradet TC, Nagaswami C, Chernysh IN, Borowski MK, Surrey S, Weisel JW
Fibrinogen Philadelphia, a hypodysfibrinogenemia characterized by abnormal polymerization and fibrinogen hypercatabolism due to {gamma} S378P mutation.
Blood 105(8):3162-3168, 2005.
PMID: 15632207 abstract
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Addya S, Keller, MA, Delgrosso K, Ponte, CM, Vadigepalli, R, Gonye, G and Surrey, S
Erythroid-induced Commitment of K562 cells results in clusters of differentially-expressed genes enriched for specific transcription regulatory elements.
Physiol. Genomics 19:117-130, 2004.
PMID: 15252187 abstract
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Sharan K, Surrey S, Ballas S, Borowski M, Devoto M, Wang KF, Sandler E, Keller M
Association of T-786C eNOS gene polymorphism with increased susceptibility to acute chest syndrome in females with sickle cell disease.Br J Haematol 124(2):240-243, 2004.
PMID: 14687036 abstract
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Kohli-Kumar, M., Marandi, H., Keller, MA, Guertin, K., Hvizdala, E
Use of hydroxyurea and recombinant erythropoietin in management of homozygous beta thalassemia. J Pediatr Hematol Oncol 24(9):777-8, 2002.
PMID: 12468925 abstract
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Keller, MA, Delgrosso, K, Surrey, S, and E Schwartz
Identification of the nucleotide change (CAC->CGC) responsible for Hb P-Galveston (Beta 117 (G19) His->Arg).
Hemoglobin 24(2):165-167, 2000.
PMID: 10870891 abstract
Schnur, RE, Gao, M, Wick, PA, Keller, M, Benke, PJ, Edwards, MJ, Grix, AW, Hockey, A, Jung, JH, Kidd, KK, Kistenmacher, M, Levin, AV, Lewis, RA, Musarella, MA, Nowakowski, RW, Orlow, SJ, Pagon, RS, Pillers, DA, Punnett, HH, Quinn, GE, Tezcan, K, Wagstaff, J, and RG Weleber.
OA1 mutations and deletions in X-linked ocular albinism.
Am. J. Hum. Genet 62(4):800-809, 1998.
PMID: 9529334 abstract
Kattamis, A.C., Kelly, K. M., Ohene-Frempong, K., Reilly, M.P., Keller, M., Cubeddu, R., Adachi, K. Surrey, S. and P. Fortina
Hb Osler [β145 (HC2) Tyr->Asn] results from post-translational modification.
Hemoglobin 21(2):109-120, 1997.
PMID: 9101280 abstract
Keller, M.A., McKenzie, S.E., Cassel, D.L., Rappaport, E.F., Schwartz, E., Surrey, S
Lineage-specific alternative splicing of the human FcγRIIA transmembrane exon requires sequences around the 3'-splice site.
Gene Expression 4:217-225, 1995.
PMID: 7787414 abstract
Keller, M.A., Cassel, D.L., Rappaport, E.F., McKenzie, S.E., Schwartz, E. and Surrey
S.:Flourescence-based RT-PCR analysis: Determination of ratios of soluble to membrane FcγRIIA transcripts.
PCR Methods and Applications 3:32-38, 1993.
PMID: 8220183 abstract
Cassel, D., Keller, M.A., Surrey, S., Schwartz, E., Schreiber, A.D., Rappaport, E.F. and McKenzie, S.E
Differential expression of FcγRIIA, FcγRIIB and FcγRIIC in hematopoietic cells: Analysis of transcripts.
Mol. Immunol 30:451-460, 1993.
PMID: 8464427 abstract
Rappaport, E.F., Cassel, D.L., Walterhouse, D.O., McKenzie, S.E., Surrey, S., Keller, M.A., Poncz, M., Chien, P., Schreiber, A.D. and Schwartz, E
A soluble form of the human Fcγ receptor, FcγRIIA: cloning, transcript analysis and detection.
Exper. Hematol 21:689-696, 1993.
PMID: 8513871 abstract
McKenzie, S.E., Keller, M.A., Cassel, D.L., Schreiber, A.D., Schwartz, E., Surrey, S. and E.F. Rappaport
Characterization of the 5'-flanking transcriptional regulatory region of the human Fcγ receptor gene, FcγRIIA.
Molecular Immunology 29:1165-1174, 1992.
PMID: 1382218 abstract
Books and Book Chapters
Vaddi, K., Keller, M, and R.C. Newton.
The Chemokine Factsbook
Academic Press, London, United Kingdom. 1997.
Keller, MA
"Molecular Diagnostic Testing for Inherited Thrombophilia using Invader®" (pp. 107-120) in Microarrays in Clinical Diagnostics (Methods in Molecular Medicine series).
Humana Press, 2005.
PMID: 16156100 abstract
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