Dr. Thomas Eddinger

Dr. Thomas EddingerMarquette University

Wehr Life Sciences, B04

MilwaukeeWI53201United States of America(414) 288-1483thomas.eddinger@marquette.edu

Professor, Director of Undergraduate Studies

Smooth muscle function

Publications

Education

B.S., 1980, Purdue University, West Lafayette, IN
M.S., 1982, University of Wisconsin-Madison 
Ph.D., 1984, University of Wisconsin-Madison
Postdoctoral Fellow, University of Wisconsin Medical School and University of Virginia Medical School

Courses Taught

BIOL 4701, Human Physiology
BIOL 1002, General Biology 2

Research Interests

Molecular Mechanisms of Smooth Muscle Function

Muscle cells are unique in their ability to generate large amounts of force in a short period of time. In skeletal, cardiac and smooth muscle cells the method by which force is generated, the time scale required, and the mechanism for regulation are similar but yet unique. The differences within and between these tissues allow them to maximally perform their required functions.

One of the many differences between the muscle types are the contractile proteins themselves--the proteins directly involved in force generation. The major contractile proteins, actin and myosin, show tissue-specific types. These isoforms allow optimization of each muscle type for its specific function, including variation in speed of shortening, amount of force generated, and energy consumption. Differences in numerous other proteins within these cells, as well as their anatomical organization, regulatory mechanisms, innervation, etc., all contribute to the diversity between these tissues.

Research work in this lab involves the study of contractile, regulatory and cytoskeletal proteins in muscle including their  expression, regulation and function in SM contraction. Molecular, mechanical, biochemical, histochemical, and immunological approaches are used to further our understanding of the function and regulation of these proteins and their isoforms.

In addition to this work I collaborate with Dr. John LaDisa in the Biomedical Engineering Department on Coarctation of the aorta (CoA). CoA is a constriction of the proximal descending thoracic aorta and is one of the most common congenital cardiovascular defects. Treatments for CoA have improved life expectancy. However, these individuals still suffer a reduced average lifespan and morbidity resulting from cardiovascular disease, mostly due to hypertension. Identifying the mechanisms of morbidity is problematic in humans due to confounding variables such as differences in age at repair, time between correction and follow-up, severity of CoA before correction, and concurrent anomalies (e.g. bicuspid aortic valves or septal defects). To address this question, we developed a novel animal model that allows us to study CoA independent of these factors. This model replicates aortic changes in humans, and mimics correction at various durations using dissolvable suture. Our results to date using a putative clinical treatment guideline (20 mmHg pressure gradient) have revealed increased medial wall thickness and stiffening, a phenotypic shift in smooth muscle cells to the de-differentiated state, and endothelial dysfunction (decreased nitric oxide relaxation) all of which persist after correction. Microarray analysis of the aorta exposed to hypertension during the coarctation period revealed differentially expressed genes (DEG) in pathways unique to CoA and Corrected groups. These DEG include those associated with excitation contraction coupling that explain our findings, as well as unanticipated metabolic pathway genes, and have elucidated therapeutic options not previously considered for CoA patients.

Based on these findings, we hypothesize that the extent of vascular remodeling and endothelial dysfunction after Correction of CoA results from the severity of adverse hemodynamics caused by the coarctation, and can be mitigated by more discerning treatment guidelines or pharmacologically targeting DEG.

Publications

John F. LaDisa, Aoy Tomita-Mitchell, Karl Stamm, Kathleen Bazan, Donna K. Mahnke, Mary A. Goetsch, Brandon J. Wegter, Jesse W. Gerringer, Kathryn Repp, Oleg Palygin, Adrian P. Zietara, Mary M. Krolikowski, Thomas J. Eddinger, Abdel A. Alli, and Michael E. Mitchell. Human genotyping and an experimental model reveal NPR-C as a possible contributor to morbidity in coarctation of the aorta. Physiological Genomics Volume 51, Issue 62019 May 22, 177-185, 2019

Thomas J Eddinger. Reversible plasticity of detrusor smooth muscle: evidence for a key role of “slipping” actomyosin cross-bridges in the control of urinary bladder compliance. Am. J. Physiol. Renal. Vol. 313 no. 4, F862-F8632017 DOI: 10.1152/ajprenal.00227.2017

Thomas J Eddinger. Structure of Differentiated/Contractile Vascular Smooth Muscle Cells. In: Vascular Smooth Muscle: Structure and Function in Health and Disease. 2017. Edited by CM Hai. World Scientific Publishing Co. Singapore

Honors and Awards

National Academies Education Fellow in Life Sciences (2007)

Students

Dr. Eddinger is NOT currently accepting new Ph.D. students into his lab

Former Students:

Qian Huang, Ph.D. December 2012
Dissertation: Myosin Isoforms and regulation of tonic and phasic contraction in smooth muscle.

Yu Zhang, MS, August 2010
Dissertation: PKC-α and CPI-17 expression and spatial-temporal distribution with activation in pig stomach antrum and fundus.

Jennifer J. Sherwood, Ph.D. August, 2001
Dissertation: Expression and Mechanical Function of Arterial Smooth Muscle Cells.

Daniel P. Meer, Ph.D. August, 1996
Dissertation: Smooth Muscle Myosin Heavy Chain Isoform Levels and Unloaded Shortening Smooth Muscle Cells.

Allen Tsao, M.S., December, 1991
Thesis: Smooth Muscle Myosin Heavy Chain Isoforms.