Allen W. Cowley, Jr., PhD

Dr. Cowley is the Harry & Gertrude Hack Term Professor in Physiology and from 1980-2018 served as chair of the Department of Physiology at the Medical College of Wisconsin. He earned his doctorate in Physiology from Hahneman Medical College in Philadelphia, PA working with Dr. John Scott before joining Dr. Arthur Guyton in the Department of Physiology and Biophysics at the University of Mississippi Medical Center where he rose to the rank of Professor.

Dr. Cowley has served as President of the American Physiological Society (APS) as well as the President of the International Union of Physiological Sciences and Chair of the Council for High Blood Pressure Research of the American Heart Association (AHA). He has received the Walter Cannon, Ernest Starling, Carl Wiggers, and Ray Daggs Awards from the APS and the Novartis Award from the Council for High Blood Pressure Research and Distinguished Scientist Award from the AHA. His research has been continuously funded by the National Institutes of Health since 1971 during which time he has mentored over fifty fellows and students in his laboratory resulting in over 410 publications in peer-reviewed journals.

Dr. Cowley is an international leader in cardiovascular research. He has made seminal observations that have advanced our understanding of hypertension with a bold vision of system approaches to the understanding of complex biological functions. These contributions have ranged from studies defining the genetic basis of hypertension in both animals and humans. As a member of the Advisory Council of the National Heart, Lung, and Blood Institute of the NIH, he spearheaded efforts, which resulted in the investment of more than $100 million for the development of the needed infrastructure to link genes to complex physiological functions and diseases (programs of Genomic Applications). As President of the American Physiological Society, he was responsible for the launch in 1999 of The Journal of Physiological Genomics in a determined effort to unite the genomic and physiological sciences in the identification of functional relevance of genomic research. During his tenure as Chair of the Department of Physiology, he forged the development and integration of genomics, bioinformatics, computational biology, and physiology to address questions of real clinical importance. As the Principal Investigator/Director of both NHLBI-Specialized Centers for Research (SCOR) grant and Programs for the Genetics of Hypertension Program Project Grant (PPG), his research team has applied genomic scale approaches to integrate the building blocks of molecular/cellular/genomic scale data with physiological data in an effort to understand the complex higher functions and diseases of the whole organism.

Dr. Cowley has made seminal findings related to the role of the baroreceptor reflexes, the renin-angiotensin system and vasopressin in both the short and long-term regulation of arterial blood pressure. His research has revealed the importance of the renal medullary circulation in sodium homeostasis and the long-term control of arterial pressure. He proposed the novel hypothesis and then demonstrated that small reductions of blood flow to the medulla of the kidney can produce chronic hypertension. More recent work has determined the impact of arterial pressure on the production of oxidative stress and renal injury in the renal medulla of hypertensive rats. During the past decade, he has pioneered efforts to attach systems level biology to the genome providing novel insights into the location of genes that underlie complex diseases planting the seeds for the field now referred to as “physiological genomics.”

Research Interests
Research in Dr. Cowley’s laboratory has been dedicated to advancing our understanding of physiological and genomic mechanisms that control blood pressure in normal and hypertensive states, with a specific interest in the role of the kidney and sodium homeostasis. As a systems physiologist, Dr. Cowley has eagerly applied many novel biological and engineering tools as possible to better understand the role of the kidney and sodium homeostasis in the regulation of blood pressure. This includes computer modeling, genomic/proteomic/molecular methods, and physiological approaches to study function of the level of the cell, tissue, and whole organism. Since the time of Dr. Cowley’s post-doctoral training with Dr. Arthur Guyton, he has applied systems engineering and computer modeling techniques to unravel cause-and-effect relationships of the parallel and overlapping pathways that determine arterial pressure. In the mid-90’s, he became deeply involved in the mapping and identification of genes responsible for salt-sensitive hypertension and linking the genome to complex biological functions. This work began with linkage studies intercrossing Dahl salt-sensitive (SS) rats with Brown Norway (BN) salt-resistant (SR) rats. It was followed by the development of consomic and congenic inbred strains by chromosomal substitution approaches. Published in Science (PMID:11721057), the studies yielded the first genomic map of cardiovascular, respiratory, kidney, and blood pressure-related traits, and then to fine-structure mapping of blood pressure and kidney-related phenotypes.

For years, a major interest in the Cowley Laboratory has also been on mechanisms that regulate blood flow to the renal medulla, with a focus on the effects of nitric oxide and reactive oxygen species (ROS) production in the medullary thick ascending limb. We developed unique techniques in the rat model organism (in vitro and in vivo) to determine changes in medullary blood flow in unanesthetized rats of genetically modified strains to study the consequences of the production and metabolism of ROS. We applied LC/MS spectral analysis techniques to identify mitochondrial proteins in the medullary thick ascending limb of Dahl salt-sensitive rats. Most recently, we have applied multi-omics (RNA-seq-transcriptomic and global metabolomic analyses) to study the effects of high salt diets upon renal tubular intermediate metabolism and bioenergetics. The studies proposed in this grant employ many of these techniques to study kidney function and the regulation of sodium and water homeostasis and blood pressure in rat models of salt-sensitive hypertension. These studies build upon our recent discovery of the importance of the mTOR pathways in salt-sensitive hypertension and kidney metabolism. Having experience in both experimental physiology and computational modeling and strong collaborative ties with Dr. Ranjan Dash on various research projects, has resulted in ~10 publications over the past five years.