Pharmacology

Justin L. Grobe, PhD

Portrait

Assistant Professor of Pharmacology

Contact Information

Primary Office: 2-307 Bowen Science Building
Iowa City, IA 52242
Primary Office Phone: 319-353-5789

Lab: 2-300 Bowen Science Building
Iowa City, IA 52242
Phone: 319-353-5803

Email: justin-grobe@uiowa.edu
Web: Department of Pharmacology

Education

BA, Biology and Chemistry, Hope College, Holland, MI
BS, Biology and Chemistry, Hope College, Holland, MI
PhD, Pharmacodynamics, University of Florida, Gainesville, FL

Postdoctoral Fellow, University of Florida College of Medicine, Gainesville, FL, Physiology and Functional Genomics
Postdoctoral Fellow, University of Iowa Carver College of Medicine, Internal Medicine (8/26-6/10) & Pharmacology (7/10-10/10)

Education/Training Program Affiliations

Biosciences Graduate Program
Department of Pharmacology Graduate Program
Interdisciplinary Graduate Program in Molecular and Cellular Biology
Interdisciplinary Graduate Program in Neuroscience
Medical Scientist Training Program

Research Summary

My laboratory is generally focused on understanding neural control of cardiovascular and metabolic function. We employ a wide range of pharmacological and physiological methods, along with new genetically-modified animal models of health and disease. We currently focus on four major areas of inquiry:

1. The control of cardiovascular and metabolic function by the brain renin-angiotensin system. The renin-angiotensin system, a circulating hormone system that is very important for blood pressure control, is used in various tissues (e.g. - kidney, heart, adipose, brain) for paracrine/autocrine/intracrine signaling. One of our projects is aimed at mapping the neural circuitry that underlies the control of blood pressure and metabolic rate. Greater understanding of these mechanisms should lead to the development of novel therapeutics for obesity and obesity-hypertension.

2. The regulation of resting metabolic rate by the adipose renin-angiotensin system. Angiotensin peptides within adipose tissues act to suppress resting metabolic rate. We are working to clarify the effects of angiotensin peptides upon adipose tissue function, and the mechanisms involved. Clarification of these mechanisms may lead to completely new classes of anti-obesity therapeutics, which work through the stimulation of resting metabolic rate (a superior method, for which there are currently no safe drug options).

3. Improving methods of assessing resting metabolic rate in vivo / role of the gut microbiome in energy balance. Previously we recognized a need for improved methods to assess resting metabolic rate, as conventional methods (respirometry) are plagued with various shortcomings. Using advanced methods (combined direct calorimetry and respirometry) we have developed a method to assess non-aerobic metabolic processes in vivo, and determined that various interventions (anesthesia, modulation of angiotensin receptors, and high fat diet) differentially modulate aerobic vs. non-aerobic processes. Ongoing work is aimed at clarifying mechanisms by which the gut microbiome controls non-aerobic resting metabolism, and continuing development of superior technologies for metabolic assessment.

4. Investigating the role of vasopressin in the pathogenesis of preeclampsia. Preeclampsia is a cardiovascular disorder of late pregnancy that includes sudden increases in blood pressure, renal damage, and fetal damage. We recently discovered that elevated arginine vasopressin secretion is a useful very-early diagnostic for this disorder in humans, and infusion of this hormone can model the disorder in mice. Ongoing studies are designed to identify the causes for increased vasopressin secretion, and the receptors involved, to develop novel drugs to prevent or treat this disorder.

Center, Program and Institute Affiliations

Cardiovascular Research Center
Center for Functional Genomics of Hypertension
Fraternal Order of Eagles Diabetes Research Center
Obesity Initiative

All Publications

Santillan M, Santillan D, Scroggins S, Min J, Sandgren J, Pearson N, Leslie K, Hunter S, Zamba G, Gibson-Corley K, Grobe J.  Vasopressin in Preeclampsia: A Novel Very-Early Human Pregnancy Biomarker and Clinically-Relevant Mouse Model..  Hypertension.  2014 October. 64(4):852-859.
[PubMed]

Burnett C, Grobe J.  Dietary effects on resting metabolic rate in C57BL/6 mice are differentially detected by indirect (O2/CO2 respirometry) and direct calorimetry.  Molecular Metabolism.  2014. 3:460-464.
[PubMed]

Burnett C, Grobe J.  Direct calorimetry identifies deficiencies in respirometry for the determination of resting metabolic rate in C57Bl/6 and FVB mice.  Am J Physiol Endocrinol Metab.  2013 October 1. 305(7).
[Link]

Littlejohn N, Siel Jr. R, Ketsawatsomkron P, Pelham C, Pearson N, Hilzendeger A, Buehrer B, Weidemann B, Li H, Davis D, Thompson A, Liu X, Cassell M, Sigmund C, Grobe J.  Hypertension in Mice with Transgenic Activation of the Brain Renin-Angiotensin System is Vasopressin-Dependent.  Am J Physiol Regul Integr Comp Physiol.  2013 May 15. 304(10):R818-R828.
[Link]

Hilzendeger A, Cassell M, Davis D, Stauss H, Mark A, Grobe J, Sigmund C.  Angiotensin Type 1a Receptors in the Subfornical Organ Are Required for Deoxycorticosterone Acetate-Salt Hypertension.  Hypertension.  2013 March 6. 61(3):716-722.
[Link]

Keen H, Littlejohn N, Liu X, Grobe J, Sigmund C.  Adiopose Angiotensin AT2 Receptors Modulate Thermogenesis though Interactions with Epidermal Growth Factor Signaling.  Hypertension.  2013. 62:A414.

Grobe J, Claflin K.  Angiotensin AT1A Receptos on Leptin Receptor-Expressing Cells are Required for the Blood Pressure and Metabolic Rate Effects of Leptin.  Hypertension.  2013. 62:A25.

Coble J, Cassell M, Grobe J, Sigmund C.  Angiotensin production specifically within the subfornical organ induces polydipsia.  Hypertension.  2013. 62:A174.

Ketsawatsomkron P, Davis D, Hilzendeger A, Grobe J, Sigmund C.  Deoxycorticosterone Acetate (DOCA)-Salt Exacerbates Hypertension and Vascular Dysfunction in Mice Expressing Dominant Negative Peroxisome Proliferator-Activated Receptor-Gamma (PPARG) in Smooth Muscle.  Hypertension .  2013. 62:A310.

Burnett C, Grobe J.  Direct calorimetry identifies deficiencies in respirometry for the determination of resting metabolic rate in C57Bl/6 and FVB mice.  American Journal of Physiology: Endocrinology & Metabolism.  2013. 305(7):E916-E924.
[PubMed]

Littlejohn N, Siel, Jr. R, Ketasawatsomkron P, Pelham C, Pearson N, Hilzendeger A, Buehrer B, Weidemann B, Li H, Davis D, Thompson A, Liu X, Cassell M, Sigmund C, Grobe J.  Hypertension in Mice with Transgenic Activation of the Brain Renin-Angiotensin System is Vasopressin-Dependent.  American Journal of Physiology: Regulatory, Integrative & Comparative Physiology.  2013. 304(10):R818-R828.
[PubMed]

Li W, Peng H, Mehaffey E, Kimball C, Grobe J, van Gool J, Sullivan M, Earley S, Danser A, Ichihara A, Feng Y.  Neuron-Specific (Pro)renin Receptor Knockout Prevents the Development of Salt-Sensitive Hypertension.  Hypertension.  2013. 63(2).
[Link]

Folchert M, Littlejohn N, Liu X, Grobe J, Sigmund C.  Physiological characterization of a selective knockout of the intracellular isoform of renin in the brain in mice.  Hypertension.  2013. 62:A16.

Jo F, Jo H, Hilzendeger A, Cassell M, Rutkowski D, Davisson R, Grobe J, Sigmund C.  Role of Endoplasmic Reticulum Stress in the SFO in Fluid Balance and Metabolic Effects of Brain Renin-Angiotensin System Activation.  Hypertension.  2013. 62:A176.

Lu K, Weatherford E, Ketsawatsomkron P, Grobe J, Sigmund C.  Transcriptional regulation of renin by nuclear receptors co-regulated with renin.  Hypertension.  2013. 62:A191.

Grobe J, Rahmouni K, Liu X, Sigmund C.  Metabolic rate regulation by the renin-angiotensin system: brain vs. body..  Pflugers Arch - European J of Physiology.  2013 January. 465(1):167-175.
[Link]

Grobe J, Rahmouni K.  Editorial Commentary: The adipose-circulating renin-angiotensin system cross-talk enters a new dimension..  Hypertension.  2012 December. 60(6):1389-1390.
[PubMed]

Ketsawatsomkron P, Lorca R, Keen H, Weatherford E, Liu X, Pelham C, Grobe J, Faraci F, England S, Sigmund C.  PPARγ regulates resistance vessel tone through a mechanism involving RGS5-mediated control of protein kinase C and BKCa channel activity..  Circ Res.  2012 November 9. 111(11):1446-1458.
[Link]

Pelham C, Ketsawatsomkron P, Groh S, Grobe J, de Lange W, Ibeawuchi S, Keen H, Weatherford E, Faraci F, Sigmund C.  Cullin-3 Regulates Vascular Smooth Muscle Function and Arterial Blood Pressure via PPARγ and RhoA/Rho-Kinase.  Cell Metab.  2012 October 3. 16(4):462-472.
[Link]

Hilzendeger A, Morgan D, Brooks L, Dellsperger D, Liu X, Grobe J, Rahmouni K, Sigmund C, Mark A.  A brain leptin-renin angiotensin system interaction in the regulation of sympathetic nerve activity.  Am J Physiol Heart Circ Physiol.  2012 July 15. 303(2):H197-H206.
[Link]

Grobe J, Park S, Liu X, Sigmund C.  Angiotensinergic signaling in the brain controls whole-body metabolism: Role of adipose AT2 receptors.  Gordon Research Conference: Angiotensin.  2012 February. 

Grobe J, Rahmouni K.  Editoral Focus: A fat contribution to RAS activation and blood pressure control: evidence from angiotensinogen conditional null mice. Focus on: "Adipocyte-specific deficiency of angiotensinogen decreases plasma angiotensinogen concentration and systolic blood pressure in mice."..  Am J Physiol Regul Integr Comp Physiol.  2012 January 15. 302(2):R242-R243.
[Link]

 .  Angiotensin II Type 1a receptor in the subfornical organ is essential for blood pressure regulation and hydromineral effects in mouse models of elevated brain renin-angiotensin system activity.  Hypertension.  2012. 60:A84.

Grobe J, Park S, Littlejohn N, Buehrer B, Weidemann B, Keen H, Liu X, Sigmund C.  Angiotensin suppresses thermogenic capacity through adipose AT2 receptors.  Hypertension.  2012. 60:A20.

Grobe J, Hilzendeger A, Davis D, Davisson R, Mark A, Sigmund C.  Endoplasmic Reticulum Stress Mediates Fluid Balance and Metabolic Effects of the Brain Renin-Angiotensin System.  Hypertension.  2012. 60:A409.

 .  Selective activation of the renin-angiotensin system in the subfornical organ is sufficient to elicit fluid and sodium intake behaviors.  Hypertension.  2012. 60:A114.

Folchert M, Liu X, Grobe J, Sigmund C.  Selective Genetic Deletion of the Brain-Specific Intracellular Renin Isoform (Renin-1b) Results in Altered Metabolic and Fluid Balance Regulation.  Hypertension.  2012. 60:A634.

Littlejohn N, Siel Jr. R, Ketsawatsomkron P, Pelham C, Hilzendeger A, Buehrer B, Weidemann B, Li H, Davis D, Thompson A, Liu X, Cassell M, Sigmund C, Grobe J.  Transgenic Hyperactivity of the Brain Renin-Angiotensin System Causes Vasopressin-Dependent Hypertension.  Hypertension.  2012. 60:A126.

Li H, Weatherford E, Davis D, Keen H, Grobe J, Daugherty A, Cassis L, Allen A, Sigmund C.  Renal proximal tubule angiotensin AT1A receptors regulate blood pressure..  Am J Physiol Regul Integr Comp Physiol.  2011 October. 301(4):R1067-R1077.
[Link]

Xu D, Borges G, Davis D, Agassandian K, Sequeira Lopez M, Gomez R, Cassell M, Grobe J, Sigmund C.  Neuron- or glial-specific ablation of secreted renin does not affect renal renin, baseline arterial pressure, or metabolism.  Physiol Genomics.  2011 March 29. 43(6):286-294.
[Link]

Xu D, Borges G, Davis D, Agassandian K, Sequeira Lopez M, Gomez R, Cassell M, Grobe J, Sigmund C.  Neuron- or glial-specific ablation of secreted renin does not affect renal renin, baseline arterial pressure, or metabolism.  Physiol Genomics.  2011 March 29. 43(6):286-294.
[Link]

Grobe J, Buehrer B, Hilzendeger A, Liu X, Davis D, Xu D, Sigmund C.  Angiotensinergic signaling in the brain mediates metabolic effects of deoxycorticosterone (DOCA)-salt in C57 mice.  Hypertension.  2011 March. 57[Part 2}(3):600-607.
[Link]

Hilzendeger A, Grobe J, Mark A, Sigmund C.  Hydromineral Consequences of DOCA-Salt Treatment: AT1A Receptors in the Brain.  Hypertension.  2011. 58(5):e37.

Sepulveda M, Ketsawatsomkron P, Grobe J, Sigmund C.  Loss of function of peroxisome proliferator-activated receptor gamma (PPARG) in vascular smooth muscle augments angiotensin II (ANG) signaling.  Hypertension.  2011. 58(5):e62.

Shi P, Grobe J, Desland F, Rodriguez V, Shan Z, Richards E, Raizada M, Sumners C.  Stimulatory action of the renin-angiotensin-aldosterone system on the production of microglial derived cytokines.  Hypertension.  2011. 58(5):e37.

Grobe J, Ketsawatsomkron P, Pelham C, Siel Jr. R, Davis D, Sigmund C.  Vascular Remodeling and Dysfunction in Response to Elevated Brain Angiotensins.  Hypertension.  2011. 58(5):e43.

Grobe J, Grobe C, Beltz T, Westphal S, Morgan D, Xu D, de Lange W, Li H, Sakai K, Thedens D, Cassis L, Rahmouni K, Mark A, Johnson A, Sigmund C.  The brain Renin-angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance.  Cell Metabolism.  2010 November 3. 12(5):431-442.
[Link]

Grobe J, Dickson M, Park S, Davis D, Born E, Sigmund C.  Cardiovascular consequences of genetic variation at -6/235 in human angiotensinogen using "humanized" gene-targeted mice..  Hypertension.  2010 November. 56(5):981-987.
[Link]

Agassandian K, Grobe J, Liu X, Agassandian M, Sigmund C, Cassell M.  Evidence for intraventricular secretion of angiotensinogen and angiotensin peptides by the subfornical organ.  Hypertension.  2010. 56(5):e102.

Grobe J, Buehrer B, Xu D, Sigmund C.  Metabolic consequences of deoxycorticosterone acetate (DOCA)-salt in mice.  Hypertension.  2010. 56(5):e102.

Shenov V, Grobe J, Qi Y, Ferreira A, Fraga-Silva R, Collamat G, Bruce E, Katovich M.  17beta-Estradiol modulates local cardiac renin-angiotensin system to prevent cardiac remodeling in the DOCA-salt model of hypertension in rats..  Peptides.  2009 December. 30(12):2309-2315.
[Link]

Xu D, Borges G, Grobe J, Pelham C, Yang B, Sigmund C.  Preservation of intracellular renin expression is insufficient to compensate for genetic loss of secreted renin.  Hypertension.  2009 December. 54(6):1240-1247.
[Link]

Xu D, Borges G, Grobe J, Pelham C, Yang B, Sigmund C.  Preservation of intracellular renin expression is insufficient to compensate for genetic loss of secreted renin.  Hypertension.  2009 December. 54(6):1240-1247.
[Link]

Grobe J, Venegas-Pont M, Sigmund C, Ryan M.  PPARgamma differentially regulates energy substrate handling in brown vs. white adipose: focus on "The PPARgamma agonist rosiglitazone enhances rat brown adipose tissue lipogenesis from glucose without altering glucose uptake"..  Am J Physiol Regul Integr Comp Physiol.  2009 May. 296(5):R1325-R1326.
[Link]

Grobe J, Grobe C, Beltz T, Borges G, Cassis L, Johnson A, Sigmund C.  Hydromineral phenotypes of transgenic mice with central renin-angiotensin system hyperactivity are dependent upon adrenal steroids.  Hypertension.  2009. 54(4):e96.

Grobe J, Xu D, Sigmund C.  An intracellular renin-angiotensin system in neurons: fact, hypothesis, or fantasy.  Physiology (Bethesda).  2008 August. 23:187-193.
[Link]

Katovich M, Grobe J, Raizada M.  Angiotensin-(1-7) as an antihypertensive, antifibrotic target..  Curr Hypertens Rep.  2008 June. 10(3):227-232.
[PubMed]

Der Sarkissian S, Grobe J, Yuan L, Narielwala D, Walter G, Katovich M, Raizada M.  Cardiac overexpression of angiotensin converting enzyme 2 protects the heart from ischemia-induced pathophysiology..  Hypertension.  2008 March. 51(3):712-718.
[Link]

Grobe J, Morgan D, Rahmouni K, Sigmund C.  Enhanced Sympathetic and HPA-Axis Activity Contribute to Increased Metabolic Rate in Transgenic Mice with Overactivity of the Central Renin-Angiotensin System.  Hypertension.  2008. 52(4):e49.

Grobe J, Der Sarkissian S, Stewart J, Meszaros J, Raizada M, Katovich M.  ACE2 overexpression inhibits hypoxia-induced collagen production by cardiac fibroblasts..  Clin Sci (Lond).  2007 October. 113(8):357-364.
[Link]

Li H, Gao Y, Grobe J, Raizada M, Katovich M, Sumners C.  Potentiation of the antihypertensive action of losartan by peripheral overexpression of the ANG II type 2 receptor..  Am J Physiol Heart Circ Physiol..  2007 February. 2992(2):H727-H735.
[Link]

Grobe J, Mecca A, Lingis M, Shenoy V, Bolton T, Machado J, Speth R, Raizada M, Katovich M.  Prevention of angiotensin II-induced cardiac remodeling by angiotensin-(1-7)..  Am J Physiol Heart Circ Physiol.  2007 February. 292(2):H736-H742.
[Link]

Grobe J, Grobe C, Gall A, Sakai K, Rahmouni K, Blumberg M, Johnson A, Sigmund C.  Increased metabolic rate in transgenic mice over-expressing the central renin-angiotensin system.  Hypertension.  2007. 50(4):e82.

Grobe J, Mecca A, Mao H, Katovich M.  Chronic angiotensin-(1-7) prevents cardiac fibrosis in DOCA-salt model of hypertension..  Am J Physiol Heart Circ Physiol..  2006 June. 290(6):H2417-H2423.
[Link]

Grobe J, Katovich M.  Alterations in aortic vascular reactivity to angiotensin 1-7 in 17-beta-estradiol-treated female SD rats.  Regul Pept.  2006 January 15. 133(1-3):62-67.
[Link]

Grobe J, DerSarkissian S, Raizada M, Katovich M.  ACE2 protects cultured cardiac fibroblasts from hypoxia-reperfusion injury.  Hypertension.  2006. 48(4):e79.

Huentelman M, Grobe J, Vazquez J, Stewart J, Mecca A, Katovich M, Ferrario C, Raizada M.  Protection from angiotensin II-induced cardiac hypertrophy and fibrosis by systemic lentiviral delivery of ACE2 in rats..  Exp Physiol.  2005 September. 90(5):783-790.
[Link]

Katovich M, Grobe J, Huentelman M, Raizada M.  Angiotensin-converting enzyme 2 as a novel target for gene therapy for hypertension.  Exp Physiol.  2005 May. 90(3):299-305.
[Link]

Li H, Gao Y, Grobe J, Raizada M, Katovich M, Sumners C.  Adenoviral-mediated systemic transduction of the angiotensin II (ang II) type 2 receptor (AT2R) enhances the hypotensive action of losartan.  Molecular Therapy.  2005. 11:S244.

Katovich M, Grobe J, Raizada M.  Gene therapy for hypertension: current targets and consideration of novel targets..  Humana Press.  2005. 

Grobe J, Rowland N, Katovich M.  Role of angiotensin II and the subfornical organ in the pharmacological actions of ethanol..  Alcohol Alcohol.  2004 September. 39(5):410-417.
[Link]

Barney C, Kurylo D, Grobe J.  Thermal dehydration-induced thirst in lithium-treated rats..  Pharmacol Biochem Behav..  2003 May. 75(2):341-347.
[Link]

Burnatowska-Hledin M, Zeneberg A, roulo A, Grobe J, Zhao P, Lelkes P, Clare P, Barney C.  Expression of VACM-1 protein in cultured rat adrenal endothelial cells is linked to the cell cycle.  Endothelium.  2001. 8(1):49-63.
[PubMed]

Li H, Park S, Davis D, Sigmund R, Grobe J, Stokes J, Sigmund C.  Role of Angiotensin II AT1A Receptor in the Renal Thick Ascending Limb of Henle’s Loop and Distal Tubules.  AJP Regulatory. 

Date Last Modified: 11/18/2014 - 10:15:00