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Full-Text Articles in Medicine and Health Sciences
Loss Of Mll Phd Finger 3 Is Necessary For Mll-Enl-Induced Hematopoietic Stem Cell Immortalization, J. Chen, Donna Santillan, M. Koonce, W. Wei, R. Luo, M. Thirman, N. Zeleznik-Le, M. Diaz
Loss Of Mll Phd Finger 3 Is Necessary For Mll-Enl-Induced Hematopoietic Stem Cell Immortalization, J. Chen, Donna Santillan, M. Koonce, W. Wei, R. Luo, M. Thirman, N. Zeleznik-Le, M. Diaz
Donna A. Santillan
Reciprocal chromosomal translocations at the MLL gene locus result in expression of novel fusion proteins, such as MLL-ENL, associated with leukemia. The three PHD finger cassette, one of the highly conserved domains in MLL, is absent in all fusion proteins. This domain has been shown to interact with Cyp33, a cyclophilin which enhances the recruitment of histone deacetylases (HDAC) to the MLL repression domain and mediates HOX gene repression. Insertion of the third PHD finger of MLL into MLL-ENL allows the recruitment of Cyp33 and, subsequently, HDAC1 to the fusion protein. Furthermore, expression of the fusion protein with the PHD …
From Molecules To Medicine: A Future Cure For Preeclampsia?, Mark Santillan, Donna Santillan, Curt Sigmund, Stephen Hunter
From Molecules To Medicine: A Future Cure For Preeclampsia?, Mark Santillan, Donna Santillan, Curt Sigmund, Stephen Hunter
Donna A. Santillan
In the United States, preeclampsia (PreE) affects 5-7% of all pregnancies, yet represents 15% of all maternal-fetal morbidity and mortality. PreE causes fetal growth restriction, oligohydramnios, fetal death, and maternal seizures, stroke, cerebrovascular hemorrhage and death. It has immediate and potentially long-term effects on both the fetus and mother. To date, the molecular pathogenesis of PreE is largely unknown. Multiple pathways, including dysfunctional angiogenesis, inappropriate placentation, oxidative stress and an altered immunological milieu have been proposed as key players in the development of PreE. In addition, genetic factors in all of these pathways are essential components in the etiology of …
Bromodomain And Histone Acetyltransferase Domain Specificities Control Mixed Lineage Leukemia Phenotype, Donna Santillan, C. Theisler, A. Ryan, R. Popovic, T. Stuart, M. Zhou, S. Alkan, N. Zeleznik-Le
Bromodomain And Histone Acetyltransferase Domain Specificities Control Mixed Lineage Leukemia Phenotype, Donna Santillan, C. Theisler, A. Ryan, R. Popovic, T. Stuart, M. Zhou, S. Alkan, N. Zeleznik-Le
Donna A. Santillan
A critical unanswered question about mixed lineage leukemia (MLL) is how specific MLL fusion partners control leukemia phenotype. The MLL-cyclic AMP-responsive element binding protein-binding protein (CBP) fusion requires both the CBP bromodomain and histone acetyltransferase (HAT) domain for transformation and causes acute myelogenous leukemia (AML), often preceded by a myelodysplastic phase. We did domain-swapping experiments to define whether unique specificities of these CBP domains drive this specific MLL phenotype. Within MLL-CBP, we replaced the CBP bromodomain or HAT domain with P300/CBP-associated factor (P/CAF) or TAF(II)250 bromodomains or the P/CAF or GCN5 HAT domains. HAT, but not bromodomain, substitutions conferred enhanced …
Cell Encapsulation As A Potential Nondietary Therapy For Maternal Phenylketonuria, Donna Santillan, Mark Santillan, Stephen Hunter
Cell Encapsulation As A Potential Nondietary Therapy For Maternal Phenylketonuria, Donna Santillan, Mark Santillan, Stephen Hunter
Donna A. Santillan
OBJECTIVE: The objective of this work was to determine whether cells overexpressing phenylalanine (Phe) hydroxylase (PAH) can significantly reduce Phe in vitro for potential use as a therapy for preventing maternal phenylketonuria. STUDY DESIGN: Human 293T and WRL68 cell lines were transiently and stably transfected to overexpress PAH. Cells were encapsulated within microspheres of sodium alginate. Timed measurements of Phe in media were performed using tandem mass spectrometry. RESULTS: Both nonencapsulated and encapsulated transiently transfected cells overexpressing PAH significantly reduced the Phe concentration in media by approximately 50% in comparison to mock-transfected cells. Cell line clones stably expressing PAH significantly …
Protective Immunization In Mice Against Group B Streptococci Using Encapsulated C5a Peptidase, Donna Santillan, M. E. Andracki, S. K. Hunter
Protective Immunization In Mice Against Group B Streptococci Using Encapsulated C5a Peptidase, Donna Santillan, M. E. Andracki, S. K. Hunter
Donna A. Santillan
OBJECTIVE: The purpose of the study was to test whether C5a peptidase encapsulated within a biodegradable polymer can act as a vaccine and elicit an immune response to prevent group B streptococci (GBS) infection in mice and provide protection to pups. STUDY DESIGN: C5a peptidase was encapsulated in semipermeable microspheres of poly(lactide-co-glycolide). Female ICR mice were immunized with encapsulated C5a peptidase, free C5a peptidase, or empty microparticles. Booster doses were given at days 21 and 42. Antibody responses were measured by enzyme-linked immunosorbent assay. Challenge with GBS type III was performed 4 days after the final booster in the vaginal …
Efficacy Of Polymeric Encapsulated C5a Peptidase-Based Group B Streptococcus Vaccines In A Murine Model, Donna Santillan, K. Rai, Mark Santillan, Y. Krishnamachari, A. Salem, S. Hunter
Efficacy Of Polymeric Encapsulated C5a Peptidase-Based Group B Streptococcus Vaccines In A Murine Model, Donna Santillan, K. Rai, Mark Santillan, Y. Krishnamachari, A. Salem, S. Hunter
Donna A. Santillan
OBJECTIVE: The purpose was to examine in mice the efficacy of various polymeric-encapsulated C5a peptidase vaccine formulations in eliciting a long-term immune response and preventing group B streptococcus (GBS) infection. STUDY DESIGN: C5a peptidase was encapsulated in semipermeable microspheres of poly(lactide-coglycolide) (PLGA). Female ICR mice were immunized with 0, 10, or 30 mug of encapsulated C5a peptidase within 2 different formulations of PLGA polymers. Booster doses were given at weeks 4 and 8. Antibody responses were measured by enzyme-linked immunosorbent assay at weeks 4, 8, 11, and 40. Vaginal challenges with GBS types 1a, III, and V were performed at …