Reuben Howden received a B.Sc. (hons) in Sports Science (including biomedical science) from Anglia Ruskin University, Cambridge, UK in 1999 and a Ph.D. in human blood pressure regulation from DeMontfort University, Leicester, UK in 2002. Dr. Howden then moved with his family to the USA where he completed 6 years of post-doctoral work at the National Institute of Environmental Health Sciences from 2002 to 2008. Dr. Howden joined the faculty of the Department of Kinesiology at UNC Charlotte from 2008 to present. Dr. Howden serves as the director of the Exercise Physiology Research Laboratory, in addition to Department, College and University committees. Dr. Howden is a professional member of the American Heart Association, a member of The American College of Sports Medicine, and serves as a reviewer for 7 peer-reviewed journals. Dr. Howden currently collaborates with Drs. Susan Arthur and Mike Turner in Kinesiology, Drs.Yvette Huet and Mark Clemens in the Dept. of Biology at UNCC, Dr. Steven Kleeberger at The National Institute of Environmental Health Science and Dr. Ian Swaine at Canterbury Christchurch University, UK
Howden R, Kleeberger SR. (2012) Genetic and environmental influences on gas exchange. In Comprehensive Physiology, published for The American Physiological Society by Wiley-Blackwell. 2(4), 10.1002/cphy.c110060
Howden R, Cho HY, Miller-Degraff L, Walker C, Clark JA, Myers PH, Rouse DC, Kleeberger SR. (2012) Cardiac Physiologic and Genetic Predictors of Hyperoxia-Induced Acute Lung Injury in Mice. American Journal of Respiratory Cell and Molecular Biology. 46 (4): 470-478. (Paper highlighted by Editor)
Sissung TM, Gardner ER, Piekarz RL, Howden R, Chen X, Woo S, Franke RM, Clark JA, Miller-Degraff L, Steinberg SM, Venzon D, Liewehr DJ, Kleeberger SR, Bates SE, Price DK, Rosing DR, Cabell C, Sparreboom A, Figg WD. (2010) Impact of ABCB1 allelic variants on QTc interval prolongation. Clinical Cancer Research. 17: 937-946.
Backus GS, Howden R, Fostel J, Bauer AK, Cho H-Y, Marzec J, Peden DB, Kleeberger SR. (2010). Protective Role of IL-10 in Ozone-induced Pulmonary Inflammation. Environmental Health Perspectives. 118(12): 1721 – 7.
Howden R, Liu E, Miller-DeGraff L, Keener HL, Walker C, Clark JA, Myers PH, Rouse DC, Wiltshire T, Kleeberger SR. (2008). The genetic contribution to heart rate and heart rate variability in quiescent mice. American Journal of Physiology. 295(1), H59 – 68.
Dr. Howden’s research program focuses on genetic control of cardiopulmonary function at baseline and under specific environmental conditions. Further, Dr. Howden is investigating the mechanisms associated with isometric exercise training induced reductions in human resting blood pressure.
Baseline cardiopulmonary function
Little is known about the likely complex nature of the genetic influence on cardiopulmonary control. Dr. Howden has developed a model for assessing baseline cardiopulmonary function from quiescent, unrestrained, conscious mice. In this model, electrocardiographic (ECG) is recorded by radio telemetry and pulmonary function by whole body plethysmgraphy, simultaneously. Coupling this animal model with available genetic tools, Dr. Howden has identified a number of potential candidate genes. We have identified a region (QTL) on mouse chromosome 6 that associates with between mouse strain differences in baseline heart rate (Figure 1). We are currently investigating the genetic effect of this QTL on baseline heart rate.
Figure 1. Genome-wide linkage map for baseline heart rate in 28 AXB/BXA RI strains. The X axis represents the length of the each chromosome, the left Y axis shows the Likelihood Odds Ratio. (LOD; blue line), and the right Y axis shows the degree to which either A/J (green line) or B6 (red line; parental strains) alleles increase phenotypic values. The numbers along the top of the graph indicate chromosome number. The lower horizontal line indicates suggestive linkage and the upper horizontal line indicates significant (P < 0.05) linkage. Adapted from Howden et al. (2008) Am J Physiol Heart Circ Physiol 295(1), H59 – 68.
Hyperoxia-induced cardiopulmonary responses
Prolonged hyperoxia (100% oxygen) exposure is an established animal model for Acute Lung Injury, Acute Respiratory Distress Syndrome and Bronchpulmonary Dysplasia. However, little is known about the role of the cardiovascular system in the adverse outcomes associated with these diseases. Using similar tools to those described above, continuous cardiopulmonary function can be recorded during hyperoxia exposure of genetic reference animal populations to describe the genetic contribution to exposure-induced responses. We have identified a region (QTL) on mouse chromosome 9 that associates with between mouse strain differences in heart rate responses to hyperoxia exposure (Figure 2). We are currently investigating the genetic effect of this QTL on baseline heart rate.
Figure 2. Genome-wide linkage map for heart rate responses to hyperoxia exposure in 28 AXB/BXA RI strains. The X axis represents the length of the each chromosome, the left Y axis shows the Likelihood Odds Ratio. (LOD; blue line), and the right Y axis shows the degree to which either A/J (green line) or B6 (red line; parental strains) alleles increase phenotypic values. The numbers along the top of the graph indicate chromosome number. The lower horizontal line indicates suggestive linkage and the upper horizontal line indicates significant (P < 0.05) linkage. Adapted from Howden et al. (2011) Am J Respir Cell Mol Biol. (epub ahead of print)
Isometric exercise training induced reductions in blood pressure
In recent years, low volume isometric exercise training it has been shown constituently to induce a reduction in human resting blood pressure (Figure 3). Since the exercise training is simple to perform, this paradigm could have important clinical implicates. However, little is known about the mechanisms associated with these changes in blood pressure, an understanding of which could provide the basis for maximizing the therapeutic benefit of isometric exercise training.
Figure 3. Mean ± S.D. resting systolic and diastolic blood pressure, before and during 5 weeks of double leg isometric exercise training. * = P<0.05 compared to before training. Adapted from Howden et al. (2002) Exp Physiol 87.4, 507-515.