University of Cincinnati Department of Pediatrics

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 and gene knockout mouse models to investigate in vivo mechanisms of gene regulation during cell differentiation and tissue (or organ) development.

Research in the Wiginton lab currently focuses on in vivo mechanisms of gene regulation controlling development of the small intestine and cell differentiation along the crypt-villus axis of the small intestinal epithelium. Epithelial cells differentiate, from stem cells localized in the crypt, into four major functional cell types (enterocytes, goblet cells, Paneth cells, and enteroendocrine cells). It is proposed that a discrete network of regulatory factors control these biological processes and the Wiginton lab is attempting to understand the role of various factors in this network. In addition, Dr. Wiginton’s lab is investigating the genetic programs that regulate profiles of gene expression along the various physical and temporal axes of the small intestine.

Significant variations in gene expression are observed along the cephalocaudal (horizontal) axis of the intestine within a particular cell type. These functional variations are established and maintained in the adult even though the intestinal epithelium undergoes a constant, continuous renewal. Changes in gene expression are also observed along the intestinal crypt-villus axis, related to cell differentiation status and cell migration. There are also very significant temporal changes in gene expression during fetal and early post-natal stages of intestinal development. Little is understood about how these temporal changes are orchestrated and regulated. Recent work in Dr. Wiginton’s lab indicates that Onecut factors (OC-2 and OC-3) play an important role in temporal regulation in the intestinal epithelium. These studies promise to reveal much about the mechanisms by which digestive function is established in the small 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

Dusing M, Maier E, and Wiginton D: Onecut 2 knockout mice fail to thrive during postnatal development and have aberrant duodenal gene expression patterns. (in preparation) 2009.

Maier E, Dusing M, and Wiginton D: Temporal regulation of enhancer function in intestinal epithelium: A role for Onecut factors.Journal of Biological Chemistry 281: 32263-71, 2006.