Molecular Regulation of Cell Development and Differentiation
Principal Investigator: Dale R Abrahamson
Abstract: DESCRIPTION (provided by applicant): Funds are requested to renew a Center of Biomedical Research Excellence (COBRE) at the University of Kansas Medical Center (KUMC) for an additional five year period. This COBRE has a research focus on the regulation of cell development and differentiation. During the initial, 5 year term, 6 Beginning Investigators graduated from the COBRE, and all are becoming successful, independent researchers. Five new Beginning Investigators have joined the Center and our goal is to help them become independently funded investigators as well. A PI, two co-PIs, an Internal Advisory Committee (lAC), a robust group of mentoring faculty, and an External Advisory Committee (EAC) of distinguished investigators have been assembled to achieve this goal. The Center is also designed to improve the research infrastructure at KUMC. The expected outcome will be more research productivity as reflected in joint publications and grant support based on a developmental biology theme. A Mentor has been assigned to each of the new Beginning Investigator faculty recruits, and individual mentoring plans and productivity timetables have been developed. Central features of the mentoring plans include ongoing critical evaluation of research projects by Mentors, semiannual conferences, and special training on scientific writing. We expect that each of our current junior faculty members will compete successfully for R01-level support from the NIH or other national granting agency within 3 years of joining the COBRE. Once funded, they will cycle off the grant making room for new faculty, and we have firm commitments from Department Chairs/Center Directors who will provide these recruits. Another important feature is the maintenance of 3 scientific Cores to provide research support to all of the Center's faculty. Together with an Administrative and Mentoring Core A, there are Cores supporting transgenesis (Core B), molecular profiling (Core C), and high resolution imaging (Core D). The outstanding combination of exceptional scientific talent, research environment, and substantial institutional commitment, ensure that this COBRE will continue to foster the development of a thematic, multidisciplinary research effort and enhance the ability of new investigators to compete for NIH support.
Funding Period: 2007-09-27 - 2017-06-30
more information: NIH RePORT
- Global alteration in gene expression profiles of deciduas from women with idiopathic recurrent pregnancy lossS A Krieg
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Kansas University Medical Center, Kansas City, KS 66160, USA
Mol Hum Reprod 18:442-50. 2012..In this first microarray approach to decidual gene expression in RPL patients, our data suggest that dysregulation of genes associated with cell invasion and immunity may contribute significantly to idiopathic recurrent miscarriage...
- Exome sequencing reveals a thrombopoietin ligand mutation in a Micronesian family with autosomal recessive aplastic anemiaMajed J Dasouki
Department of Pediatrics
Blood 122:3440-9. 2013....
- Cross-talk between hypoxia and insulin signaling through Phd3 regulates hepatic glucose and lipid metabolism and ameliorates diabetesCullen M Taniguchi
Division of Radiation and Cancer Biology, Department of Radiation Oncology, Center for Clinical Sciences Research, Stanford, California, USA
Nat Med 19:1325-30. 2013..Thus, isoform-specific inhibition of Phd3 could be exploited to treat type 2 diabetes without the toxicity that could occur with chronic inhibition of multiple Phd isoforms. ..
- Laminin and type IV collagen isoform substitutions occur in temporally and spatially distinct patterns in developing kidney glomerular basement membranesDale R Abrahamson
Department of Anatomy and Cell Biology and The Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas
J Histochem Cytochem 61:706-18. 2013..We conclude that different biosynthetic mechanisms control laminin and type IV collagen expression in developing glomeruli. ..
- Conserved aromatic residue confers cation selectivity in claudin-2 and claudin-10bJiahua Li
Division of Nephrology and Hypertension and The Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas 66160, USA
J Biol Chem 288:22790-7. 2013..Our findings provide new insight into how ion selectivity is achieved in the paracellular pore. ..
- Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud-to-cap stage transition in tooth developmentIrfan Saadi
Center for Regenerative and Developmental Biology, The Forsyth Institute, Cambridge, MA 02142, USA
Development 140:2697-702. 2013....
- Claudin-2 pore function requires an intramolecular disulfide bond between two conserved extracellular cysteinesJiahua Li
Division of Nephrology and Hypertension, University of Kansas Medical Center, Kansas City, Kansas 66160, USA
Am J Physiol Cell Physiol 305:C190-6. 2013..We further speculate that this role is generalizable to other claudin family members. ..
- Upregulated expression of integrin α1 in mesangial cells and integrin α3 and vimentin in podocytes of Col4a3-null (Alport) miceBrooke M Steenhard
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
PLoS ONE 7:e50745. 2012..We conclude that overexpression of mesangial integrin α1 and podocyte vimentin and integrin α3 may be important features of glomerular Alport disease, possibly affecting cell-signaling, cell shape and cellular adhesion to the GBM...
- Role of the podocyte (and glomerular endothelium) in building the GBMDale R Abrahamson
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA
Semin Nephrol 32:342-9. 2012..Stress is placed on the assembly of a compositionally correct GBM for the acquisition and maintenance of glomerular barrier properties...
- Vaginal hypersensitivity and hypothalamic-pituitary-adrenal axis dysfunction as a result of neonatal maternal separation in female miceA N Pierce
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, United States
Neuroscience 263:216-30. 2014..Together these data indicate that NMS affects both central and peripheral aspects of the HPA axis, which may drive changes in vaginal sensitivity and the development of comorbid chronic pain and mood disorders. ..
- UNMC EPPLEY CANCER CENTER SUPPORT GRANTKenneth H Cowan; Fiscal Year: 2013....
- Neurohumoral control of veins in hypertensionGregory D Fink; Fiscal Year: 2013..This project tests the idea that altered structure or function of veins also may cause hypertension, and that it may be possible to treat hypertension using drugs that affect veins. ..
- EARLY EVENTS IN ALZHEIMER PATHOGENESISSUE TILTON GRIFFIN; Fiscal Year: 2013..The synergy between our aims, approaches, and measures will enable us to meet our goal of defining early cellular interactions toward development of rational interventions in AD. ..
- Neuro-Circulatory Function in Chronic Heart FailureIrving H Zucker; Fiscal Year: 2013..The role of exercise training in modulating ROS generation and antioxidant enzymes in animals with CHF will also be investigated in this project. ..
- DIABETES AND ENDOCRINOLOGY RESEARCH CENTERDomenico Accili; Fiscal Year: 2013....
- Indiana University Center for Pediatric PharmacologyJamie L Renbarger; Fiscal Year: 2013..The direct outcome of these studies will be new biomarkers and predictive signatures that will increase the precision of the existing dosing schemas used in the treatment of childhood cancer. ..