Dan Wiginton, PhD
Appointment
Associate Professor of Pediatrics
Email
dan.wiginton@cchmc.org
Phone
513-636-4547
Fax
513-636-4317
Bio
Dan Wiginton, PhD, has been in the Department of Pediatrics at Children's Hospital and the University of Cincinnati since 1984. The principal focus of his work during that time has been basic research and research training of graduate students and postdoctoral fellows. Dr. Wiginton's current research interests are directed toward an understanding of the genetic regulatory networks that govern tissue and organ development, as well as the cell-type specific differentiation that underlies this development.
Dr. Wiginton's lab uses the human adenosine deaminase (ADA) gene as a model system to investigate tissue-specific gene expression and the mechanisms that govern it. Transgenic mouse technology has been utilized heavily in these studies, allowing investigation of these questions in vivo. With the ADA model, studies have been carried out to understand thymocyte differentiation in thymus (critical to development of the immune system) and epithelial development in small intestine (critical to normal nutrient utilization).
Prior to coming to Cincinnati, Dr. Wiginton carried out postdoctoral training at the University of Kentucky in Lexington and at the University of Texas Health Sciences Center in San Antonio under Dr. John Hutton. While at these institutions, Dr. Wiginton's research focused on characterization of the normal human ADA protein and gene, and defects in ADA structure and function that cause severe combined immunodeficiency disease(SCID). These studies included collaborations in very early studies directed toward stem cell gene therapy to correct ADA-deficient SCID. Dr. Wiginton carried out his graduate studies at the University of Texas (Austin) under Dr. William Shive. He was awarded a PhD in Biochemistry in 1978, for studies in the area of bacterial enzyme expression and regulation. These studies investigated the biosynthesis and intermediary metabolism of the branched-chain amino acids (valine/leucine/isoleucine).
Credentials
PhD: The University of Texas at Austin, 1978.
Postdoctoral Fellowship: University of Kentucky, Lexington, KY, 1978-1980.
Fellow / Chemist: Dept. of Hematology, UTHSC-San Antonio and Audie Murphy VA Hospital, San Antonio, TX, 1980-1984.
Awards and Honors
University Fellow, The University of Texas at Austin, 1973-1976.
Research
The research in Dr. Dan Wiginton's lab is devoted to the use of transgenic mouse models to investigate in vivo mechanisms of gene regulation during cell differentiation and tissue (or organ) development. The model system that is currently being exploited in these studies is the human adenosine deaminase (ADA) gene. ADA has a complex, highly regulated pattern of expression.
It is expressed in all human tissues but the expression levels vary over a range of several thousand-fold and undergo significant changes in various tissues and cell types in a developmentally specific manner. The ADA gene model is being used to investigate the regulatory events and networks that underlie this tissue-specific pattern of expression. A number of distinct genomic regions (regulatory modules) that control ADA tissue expression have been identified and characterized by the labs of Dr. Wiginton and others. These modules bind a variety of transcription factors that collaborate to control chromatin structure and activate ADA gene transcription in distinct cell types.
One cell type that exhibits very high levels of ADA expression is the enterocyte of the duodenal epithelium. Gene ablation studies by others have shown that ADA expression is essential for duodenal integrity and viability. Transgenic mouse studies in Dr. Wiginton's lab have identified and mapped an enhancer that activates high-level ADA expression specifically in duodenal enterocytes. This enhancer activates expression only in proximal duodenum (along the anterior-posterior axis of the small intestine).
The duodenal expression is limited to enterocytes in the epithelium along the villus past the crypt-villus junction (along that vertical crypt-villus axis of the intestine). The enhancer alone is capable of activating duodenal expression at two weeks of age, a developmental time point (suckling-weanling transition) at which the genes for many metabolic enzymes are activated in mice. An upstream region that appears to be a temporal regulatory module can alter the timing of activation to about the time of birth. Detailed analyses of these intestinal regulatory regions are currently underway in Dr. Wiginton's lab. These studies will give information about mechanisms of epithelial cell differentiation, regulation of positional expression, and temporal control of gene activation within the intestine.
Research Grants and Contracts
1/02-11/06, National Institutes of Health (DK 52343), Regulation of Adenosine Deaminase in Small Intestine: Wiginton D (PI).
1/98-12/00, National Institutes of Health (DK 52343), Regulation of Adenosine Deaminase in Small Intestine: Wiginton D (PI).
3/97-4/99, National Institutes of Health (DK 14770), Genetic Control of Mammalian Enzyme Expression: Wiginton D (PI).
Funded Training Programs: Pulmonary and Cardiovascular Development, Endocrinology and Neonatology
Publications, Most Recent
Dan Wiginton's publications as listed by PubMed
Maier E, Dusing M, and Wiginton D: Cdx binding determines the timing of enhancer activation in postnatal duodenum.Journal of Biological Chemistry 280: 13195-13202, 2005.
Dusing M and Wiginton D: Epithelial lineages of the small intestine have unique patterns of GATA expression.Journal of Molecular Histochemistry 36: 15-24, 2005.
Dusing M, Florence E, and Wiginton D: High-level activation by a duodenum specific enhancer requires functional GATA binding sites. American Journal of Physiology 284: G1053-G1065, 2003.
Bates M, Erwin C, Sanford L, Wiginton D, Bezerra J, Schatzman L, Jegga A, Ley-Ebert C, Williams S, Steinbrecher K, Warner B, Cohen M, and Aronow B: Novel genes and functional relationships in the adult mouse gastrointestinal tract identified by microarray analysis. Gastroenterology 122: 1467-1482, 2002.
Dusing M, Florence E, and Wiginton D: PDX-1 is required for activation in vivo from a duodenum-specific enhancer.Journal of Biological Chemistry 276:14434-14442, 2001.
Dusing M, Brickner A, Thomas M, and Wiginton D: A duodenal-specific enhancer regulates expression along three axes in the small intestine. American Journal of Physiology 279:G1080-G1093, 2000.
Professional Organization Memberships
Service
Editorial Board, Gene Therapy and Molecular Biology.
Special Interests
- Gene regulation and development
- Regulatory factor networks
- Enhancers
- Chromatin Modulation
Presentations
Dusing M and Wiginton D: Intestinal Epithelial Lineages Have Unique Patterns of GATA Expression FASEB.Summer Conference - Gastrointestinal Tract XI: Innovations in GI Research and Therapy, Snowmass, CO, August 2005.
Florence E, Dusing M and Wiginton D: Regulation of adenosine deaminase in duodenum.Experimental Biology 2003 Joint National Meeting of ASBMB with five other FASEB Societies, San Diego, CA, 2003.
Dusing M, Florence E, and Wiginton D: Role of GATA and Cdx factors in a duodenum-specific enhancer experimental biology.Joint National Meeting of ASBMB with six other FASEB Societies, New Orleans, LA, 2002.
Related Areas
This person works in these other areas at Cincinnati Children's Hospital Medical Center:
