Seth W. Holwerda, Ph.D.

Professional Background

My scientific career has focused on understanding the neural and vascular mechanisms that regulate human cardiovascular function in health and disease. I earned a B.S. in Kinesiology from the University of Texas at Austin, an M.S. in Exercise Physiology from the University of Texas at Arlington, and a Ph.D. in Physiology from the University of Missouri, where my doctoral research examined autonomic regulation and blood pressure control in type 2 diabetes. I subsequently completed a NIH-supported postdoctoral fellowship in vascular physiology at the University of Iowa, expanding my expertise in human integrative physiology, sympathetic neural control of the circulation, vascular function, and cardiovascular disease mechanisms.

In 2020, I joined the University of Kansas Medical Center as a faculty member in the Department of Anesthesiology, Pain and Perioperative Medicine, with a joint appointment in the Department of Cell Biology and Physiology. I direct a translational human physiology research program that combines advanced autonomic testing, microneurography, vascular imaging, and interventional clinical studies to investigate mechanisms of hypertension, obesity-related cardiovascular disease, and autonomic dysfunction.

My laboratory has been supported by an NHLBI R01 investigating sympathetic-vascular dysfunction in obesity-related hypertension and the NIH RECOVER-AUTONOMIC clinical trial evaluating treatments for autonomic dysfunction and postural orthostatic tachycardia syndrome (POTS) following SARS-CoV-2 infection. My research has resulted in more than 45 peer-reviewed publications in leading cardiovascular and physiology journals.

Beyond research, I am committed to mentoring the next generation of physician-scientists and biomedical investigators. I mentor graduate and medical students, serve as a member of the KUMC Institutional Review Board and the KU Clinical and Translational Science Institute Scientific Advisory Board, and actively participate in NIH grant review panels, NASA grant review panels, and scientific journal editorial activities. My goal is to foster collaborative, multidisciplinary research that advances our understanding of cardiovascular physiology while translating mechanistic discoveries into improved patient care.

• PhD, Medical Pharmacology & Physiology, University of Missouri
• Post Doctoral Fellowship, Vascular Physiology, University of Iowa, Iowa City, IA

Research

Overview

My research program investigates the physiological mechanisms by which metabolic and autonomic disorders increase cardiovascular risk in humans. By integrating fundamental cardiovascular physiology with translational clinical research, my laboratory examines how obesity, insulin resistance, dyslipidemia, chronic pain, and post-viral autonomic dysfunction alter neural control of the circulation, vascular function, and blood pressure regulation. The overarching goal is to identify mechanisms that contribute to cardiovascular disease before overt clinical complications develop.

A major focus of my work is understanding how the sympathetic nervous system regulates vascular tone and blood pressure. We use microneurography, beat-to-beat hemodynamic monitoring, vascular ultrasound, retinal microvascular imaging, transcranial Doppler ultrasound, and targeted pharmacological interventions to study interactions between sympathetic nerve activity and vascular responsiveness. Our research addresses sympathetic-vascular transduction, arterial baroreflex function, endothelial and microvascular dysfunction, oxidative stress, inflammation, and blood pressure variability.

My NIH-funded research examines why obesity-related metabolic dysfunction sensitizes the vasculature to sympathetic activation. We are particularly interested in how circulating lipids, insulin resistance, oxidative stress, inflammation, adrenergic signaling, and vascular smooth muscle pathways contribute to exaggerated vasoconstriction and unstable blood pressure. These mechanistic human studies are designed to identify pathways that may become therapeutic targets for hypertension and obesity-related cardiovascular disease.

A complementary area of my research focuses on postural orthostatic tachycardia syndrome and autonomic dysfunction associated with Long COVID. As site principal investigator for the NIH RECOVER-AUTONOMIC clinical trial, I oversee autonomic phenotyping and participate in multicenter trials evaluating pharmacological and nonpharmacological treatments for patients with persistent autonomic symptoms after SARS-CoV-2 infection.

Ultimately, my laboratory seeks to bridge mechanistic physiological discovery with clinical investigation. By defining the neural and vascular abnormalities that precede cardiovascular disease, we aim to develop better biomarkers, identify therapeutic targets, and improve treatment for patients with metabolic and autonomic disorders.