Nathan Tykocki, PhD

he/his/him
Associate Professor and Cubi³C Core Director
Pharmacology and Toxicology

Bio

My research focuses on urinary bladder physiology, with specific emphasis on the bladder afferent nerves and the bladder vasculature as major regulators of bladder function. Presently, my work discovered that (1) transient contractions of the bladder wall generate bursts of afferent nerve activity that dominate sensory outflow from the bladder; (2) the vasculature of the urinary bladder, due to the unique physiological demands it experiences during bladder filling, possesses distinct contractile properties versus other vessels of similar size; and (3) social stress alone is sufficient to cause progressive bladder dysfunction that moves from overactivity to underactivity as stress duration/intensity increases. We employ a multi-disciplinary approach, including biochemical, pharmacological, physiological and genetic tools, to understand how the bladder muscle, nerves, vasculature and urothelium communicate to impact bladder function in health and disease. My scientific training explored vascular smooth muscle biology, physiology and pharmacology, specifically in terms of calcium signaling pathways as regulators of smooth muscle contractility. My fields of expertise include in vivo physiology, myography, receptor pharmacology, confocal microscopy, fluorescence microscopy, calcium imaging, immunofluorescence, and instrumentation design/fabrication.

Colleges

• College of Human Medicine
• College of Osteopathic Medicine

Programs

• Neuroscience Program Executive Committee Member
• Integrated Pharmacological Sciences Training Program
• Doctor of Philosophy in Pharmacology and Toxicology
• Undergraduate Minor in Pharmacology and Toxicology Advisor

Facilities

• MSU Cubi³C (Director)

Education

• Ph.D., Pharmacology and Toxicology, Pharmacology and Toxicology, Michigan State University (2007-09-01—2012-08-01)
• B.S., Science and Technology Studies, Lyman Briggs College, Michigan State University (1998-09-01—2002-04-01)

Funding

• Bladder Wall Stiffness Drives Sensation of Fullness, National Institute of Diabetes and Digestive and Kidney Diseases (2023-12-01—2027-11-30)
• Bladder Blood Flow and Vascular Contractility Regulate Bladder Function, National Institute of Diabetes and Digestive and Kidney Diseases (2015-09-01—2020-08-31)
• TRPV1 Mediates Progressive Stress-Induced Bladder Dysfunction, National Institute of Diabetes and Digestive and Kidney Diseases (2019-06-19—2024-04-30)
• Michigan Interdisciplinary Center for Urology Research and Education (MI-CURE), National Institute of Diabetes and Digestive and Kidney Diseases (2021-09-22—2023-07-31)

Works

• Quantifying whole bladder biomechanics using the novel pentaplanar reflected image macroscopy system. Biomechanics and Modeling in Mechanobiology (2023)
• The mast cell stimulator Compound 48/80 causes urothelium-dependent increases in murine urinary bladder contractility. American journal of physiology. Renal physiology (2023)
• Compound 48/80 increases murine bladder wall compliance independent of mast cells. Scientific Reports (2023)
• Genetic ablation of smooth muscle KIR2.1 is inconsequential to the function of mouse cerebral arteries. Journal of Cerebral Blood Flow & Metabolism (2022)
• Histamine receptors rapidly desensitize without altering nerve-evoked contractions in murine urinary bladder smooth muscle. American Journal of Physiology-Renal Physiology (2022-03-01)
• Identification of Piezo1 channels in perivascular adipose tissue (PVAT) and their potential role in vascular function. Pharmacological Research (2022)
• Remodeling of extracellular matrix in the urinary bladder of paraplegic rats results in increased compliance and delayed fiber recruitment 16 weeks after spinal cord injury. Acta Biomaterialia (2022)
• A mechanism linking perinatal 2,3,7,8 tetrachlorodibenzo-p-dioxin exposure to lower urinary tract dysfunction in adulthood. Disease Models & Mechanisms (2021)
• Reflected image macroscopy system. United States Patent Office (2020-03-10)
• New direct evidence that histamine augments bladder sensory outflow during filling is nothing to sneeze at. American Journal of Physiology-Renal Physiology (2020-02-01)
• Excitability and contractility in arterioles and venules from the urinary bladder. Current Topics in Membranes (2020)
• The KV 7 channel activator retigabine suppresses mouse urinary bladder afferent nerve activity without affecting detrusor smooth muscle K+ channel currents. The Journal of physiology (2018)
• The KV7 channel activator retigabine suppresses mouse urinary bladder afferent nerve activity without affecting detrusor smooth muscle K+ channel currents. The Journal of Physiology (2019)
• Development of stress-induced bladder insufficiency requires functional TRPV1 channels. American journal of physiology. Renal physiology (2018)
• Capillary K+-sensing initiates retrograde hyperpolarization to increase local cerebral blood flow. (2017)
• Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles. (2017)
• Inhibition of vascular smooth muscle inward-rectifier K+ channels restores myogenic tone in mouse urinary bladder arterioles. (2017)
• Transient contractions of urinary bladder smooth muscle are drivers of afferent nerve activity during filling. (2016)
• Synthetic Peptides as cGMP-Independent Activators of cGMP-Dependent Protein Kinase Iα. (2015)
• Divergent signaling mechanisms for venous versus arterial contraction as revealed by endothelin-1. (2015)
• Social stress in mice induces urinary bladder overactivity and increases TRPV1 channel-dependent afferent nerve activity. (2015)
• Location, Location, Location: Juxtaposed calcium-signaling microdomains as a novel model of the vascular smooth muscle myogenic response. (2015)
• Transglutaminase activity is decreased in large arteries from hypertensive rats compared with normotensive controls. (2015)
• Measurement of smooth muscle function in the isolated tissue bath-applications to pharmacology research. (2015)
• Ryanodine receptors are uncoupled from contraction in rat vena cava. Cell Calcium (2013)
• One-month serotonin infusion results in a prolonged fall in blood pressure in the deoxycorticosterone acetate (DOCA) salt hypertensive rat. (2013)
• Reverse-mode Na+/Ca2+ exchange is an important mediator of venous contraction. (2012)
• Expression and potential function of prion protein in the vasculature. Reinvention: And International Journal of Undergraduate Research (2011)
• The interdependence of endothelin-1 and calcium: a review. (2010)
• Endothelin ET(B) receptors in arteries and veins: multiple actions in the vein. (2009)

Employment

• Associate Professor, Michigan State University (2024-07-01)
• Assistant Professor, Michigan State University (2019-02-01—2024-06-30)
• Research Assistant Professor, University of Vermont College of Medicine (2015-07-01—2019-01-31)
• Postdoctoral Associate, University of Vermont College of Medicine (2012-08-01—2015-06-30)
• Research Associate, Michigan State University (2006—2007)
• Donor Recruitment Representative, American Red Cross (2005—2006)
• Admissions Adviser, Baker College of Owosso (2004—2005)
• Professional Sales Representative, Ventiv Health (2002—2004)