Scholars@Duke
Gentzon Hall

Gentzon Hall

Assistant Professor of Medicine
Medicine, Nephrology
gentzon.hall@duke.edu
Dept of Medicine, Box 31108 DUMC, Durham, NC 27710

Selected Publications

Mechanistic Insights Into Redox Damage of the Podocyte in Hypertension.

Journal Article Hypertension · November 13, 2024 Podocytes are specialized cells within the glomerular filtration barrier, which are crucial for maintaining glomerular structural integrity and convective ultrafiltration. Podocytes exhibit a unique arborized morphology with foot processes interfacing by s ... Full text Link to item Cite

Genetic insights into the mechanisms of proliferative glomerulonephritis.

Journal Article J Clin Invest · August 1, 2024 Glomerular visceral epithelial cells (i.e., podocytes) are an essential component of the tripartite glomerular filtration barrier. Healthy podocytes are terminally differentiated cells with limited replicative capacity; however, inappropriate cell cycle re ... Full text Link to item Cite

Swollen Feet: Considering the Paradoxical Roles of Interleukins in Nephrotic Syndrome.

Journal Article Biomedicines · March 26, 2024 Interleukins are a family of 40 bioactive peptides that act through cell surface receptors to induce a variety of intracellular responses. While interleukins are most commonly associated with destructive, pro-inflammatory signaling in cells, some also play ... Full text Link to item Cite

Interleukin-15 in kidney disease and therapeutics.

Journal Article Curr Opin Nephrol Hypertens · March 1, 2024 PURPOSE OF REVIEW: Interleukin 15 (IL-15) is a member of the IL-2 family of common gamma chain receptor cytokines with well described anti-inflammatory, pro-survival and pro-proliferative signaling properties. The cytoprotective role of IL-15 in the kidney ... Full text Link to item Cite

β-Arrestin pathway activation by selective ATR1 agonism promotes calcium influx in podocytes, leading to glomerular damage.

Journal Article Clin Sci (Lond) · December 22, 2023 Angiotensin receptor blockers (ARBs) are the first-line treatment for hypertension; they act by inhibiting signaling through the angiotensin 1 receptor (AT1R). Recently, a novel biased AT1R agonist, TRV120027 (TRV), which selectively activates the β-arrest ... Full text Link to item Cite

Tobacco exposure in adults and children with proteinuric glomerulopathies: a NEPTUNE cohort study.

Journal Article BMC Nephrol · February 9, 2023 BACKGROUND: Tobacco exposure has been recognized as a risk factor for cardiovascular disease (CVD) and progression of kidney disease. Patients with proteinuric glomerulopathies are at increased risk for cardiovascular morbidity and mortality. Multiple stud ... Full text Link to item Cite

JAK inhibitor blocks COVID-19 cytokine-induced JAK/STAT/APOL1 signaling in glomerular cells and podocytopathy in human kidney organoids.

Journal Article JCI Insight · June 8, 2022 COVID-19 infection causes collapse of glomerular capillaries and loss of podocytes, culminating in a severe kidney disease called COVID-19-associated nephropathy (COVAN). The underlying mechanism of COVAN is unknown. We hypothesized that cytokines induced ... Full text Open Access Link to item Cite

IL-1 receptor signaling in podocytes limits susceptibility to glomerular damage.

Journal Article Am J Physiol Renal Physiol · February 1, 2022 Interleukin (IL)-1 receptor type 1 (IL-1R1) activation triggers a proinflammatory signaling cascade that can exacerbate kidney injury. However, the functions of podocyte IL-1R1 in glomerular disease remain unclear. To study the role of IL-1R1 signaling in ... Full text Link to item Cite

Steroid-sensitive nephrotic syndrome candidate gene CLVS1 regulates podocyte oxidative stress and endocytosis.

Journal Article JCI Insight · January 25, 2022 We performed next-generation sequencing in patients with familial steroid-sensitive nephrotic syndrome (SSNS) and identified a homozygous segregating variant (p.H310Y) in the gene encoding clavesin-1 (CLVS1) in a consanguineous family with 3 affected indiv ... Full text Link to item Cite

Twist1 in podocytes ameliorates podocyte injury and proteinuria by limiting CCL2-dependent macrophage infiltration.

Journal Article JCI Insight · August 9, 2021 The transcription factor Twist1 regulates several processes that could impact kidney disease progression, including epithelial cell differentiation and inflammatory cytokine induction. Podocytes are specialized epithelia that exhibit features of immune cel ... Full text Link to item Cite

Mechanisms of Proteinuria in HIV.

Journal Article Front Med (Lausanne) · 2021 Proteinuria is common in the setting of HIV infection, and may reflect comorbid kidney disease, treatment-related nephrotoxicity, and HIV-related glomerular diseases. The mechanisms of podocyte and tubulointerstial injury in HIV-associated nephropathy (HIV ... Full text Link to item Cite

TRPC Channels in Proteinuric Kidney Diseases.

Journal Article Cells · December 23, 2019 Over a decade ago, mutations in the gene encoding TRPC6 (transient receptor potential cation channel, subfamily C, member 6) were linked to development of familial forms of nephrosis. Since this discovery, TRPC6 has been implicated in the pathophysiology o ... Full text Link to item Cite

The Human FSGS-Causing ANLN R431C Mutation Induces Dysregulated PI3K/AKT/mTOR/Rac1 Signaling in Podocytes.

Journal Article J Am Soc Nephrol · August 2018 BACKGROUND: We previously reported that mutations in the anillin (ANLN) gene cause familial forms of FSGS. ANLN is an F-actin binding protein that modulates podocyte cell motility and interacts with the phosphoinositide 3-kinase (PI3K) pathway through the ... Full text Link to item Cite

Genetic Testing for Steroid-Resistant-Nephrotic Syndrome in an Outbred Population.

Journal Article Front Pediatr · 2018 Background: Steroid-resistant nephrotic syndrome (SRNS) is a leading cause of end-stage kidney disease in children and young adults. Despite advances in genomic science that have led to the discovery of >50 monogenic causes of SRNS, there are no clear guid ... Full text Link to item Cite

Genetic Causes of Chronic Kidney Disease

Chapter · January 1, 2018 Chronic kidney disease (CKD) is a major cause of morbidity and mortality worldwide, affecting an estimated 10% of the world population. There are many causes for CKD, including familial diseases. This chapter will discuss the genetics of two of the major c ... Full text Cite

Losing their footing: Rac1 signaling causes podocyte detachment and FSGS.

Journal Article Kidney Int · August 2017 Selective modulation of Rho GTPase activity in podocytes recapitulates characteristic features of human nephrosis. Using a mouse model, Robins et al. found that high levels of Rac1 activation in podocytes caused podocyte detachment and glomerulosclerosis. ... Full text Link to item Cite

Dysregulation of WTI (-KTS) is Associated with the Kidney-Specific Effects of the LMX1B R246Q Mutation.

Journal Article Sci Rep · January 6, 2017 Mutations in the LIM homeobox transcription factor 1-beta (LMX1B) are a cause of nail patellar syndrome, a condition characterized by skeletal changes, glaucoma and focal segmental glomerulosclerosis. Recently, a missense mutation (R246Q) in LMX1B was repo ... Full text Link to item Cite

Rare variants in tenascin genes in a cohort of children with primary vesicoureteric reflux.

Journal Article Pediatr Nephrol · February 2016 BACKGROUND: Primary vesicoureteral reflux (PVUR) is the most common malformation of the kidney and urinary tract, and reflux nephropathy is a major cause of chronic kidney disease in children. Recently, we reported mutations in the tenascin XB gene (TNXB) ... Full text Link to item Cite

Variability in phenotype induced by the podocin variant R229Q plus a single pathogenic mutation.

Journal Article Clin Kidney J · October 2015 BACKGROUND: Mutations in podocin (NPHS2) are the most common cause of childhood onset autosomal recessive steroid-resistant nephrotic syndrome (SRNS). The disease is characterized by early-onset proteinuria, resistance to immunosuppressive therapy and rapi ... Full text Open Access Link to item Cite

HLA-DQA1 and PLCG2 Are Candidate Risk Loci for Childhood-Onset Steroid-Sensitive Nephrotic Syndrome.

Journal Article J Am Soc Nephrol · July 2015 Steroid-sensitive nephrotic syndrome (SSNS) accounts for >80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome arra ... Full text Link to item Cite

Translating genetic findings in hereditary nephrotic syndrome: the missing loops.

Journal Article Am J Physiol Renal Physiol · July 1, 2015 Nephrotic syndrome (NS) is a clinicopathological entity characterized by proteinuria, hypoalbuminemia, peripheral edema, and hyperlipidemia. It is the most common cause of glomerular disease in children and adults. Although the molecular pathogenesis of NS ... Full text Link to item Cite

A novel missense mutation of Wilms' Tumor 1 causes autosomal dominant FSGS.

Journal Article J Am Soc Nephrol · April 2015 FSGS is a clinical disorder characterized by focal scarring of the glomerular capillary tuft, podocyte injury, and nephrotic syndrome. Although idiopathic forms of FSGS predominate, recent insights into the molecular and genetic causes of FSGS have enhance ... Full text Link to item Cite

Mutations in the gene that encodes the F-actin binding protein anillin cause FSGS.

Journal Article J Am Soc Nephrol · September 2014 FSGS is characterized by segmental scarring of the glomerulus and is a leading cause of kidney failure. Identification of genes causing FSGS has improved our understanding of disease mechanisms and points to defects in the glomerular epithelial cell, the p ... Full text Link to item Cite

Phosphodiesterase 5 inhibition ameliorates angiontensin II-induced podocyte dysmotility via the protein kinase G-mediated downregulation of TRPC6 activity.

Journal Article Am J Physiol Renal Physiol · June 15, 2014 The emerging role of the transient receptor potential cation channel isotype 6 (TRPC6) as a central contributor to various pathological processes affecting podocytes has generated interest in the development of therapeutics to modulate its function. Recent ... Full text Link to item Cite

Rare hereditary COL4A3/COL4A4 variants may be mistaken for familial focal segmental glomerulosclerosis

Journal Article Kidney International · January 1, 2014 Focal segmental glomerulosclerosis (FSGS) is a histological lesion with many causes, including inherited genetic defects, with significant proteinuria being the predominant clinical finding at presentation. Mutations in COL4A3 and COL4A4 are known to cause ... Full text Cite

TNXB mutations can cause vesicoureteral reflux.

Journal Article J Am Soc Nephrol · July 2013 Primary vesicoureteral reflux (VUR) is the most common congenital anomaly of the kidney and the urinary tract, and it is a major risk factor for pyelonephritic scarring and CKD in children. Although twin studies support the heritability of VUR, specific ge ... Full text Link to item Cite

Inverted formin 2 mutations with variable expression in patients with sporadic and hereditary focal and segmental glomerulosclerosis.

Journal Article Kidney Int · January 2012 Focal and segmental glomerulosclerosis (FSGS) is a major cause of end-stage kidney disease. Recent advances in molecular genetics show that defects in the podocyte play a major role in its pathogenesis and mutations in inverted formin 2 (INF2) cause autoso ... Full text Link to item Cite

Hepatorenal correction in murine glycogen storage disease type I with a double-stranded adeno-associated virus vector.

Journal Article Mol Ther · November 2011 Glycogen storage disease type Ia (GSD-Ia) is caused by the deficiency of glucose-6-phosphatase (G6Pase). Long-term complications of GSD-Ia include life-threatening hypoglycemia and proteinuria progressing to renal failure. A double-stranded (ds) adeno-asso ... Full text Link to item Cite

TRPC6 enhances angiotensin II-induced albuminuria.

Journal Article J Am Soc Nephrol · March 2011 Mutations in the canonical transient receptor potential cation channel 6 (TRPC6) are responsible for familial forms of adult onset focal segmental glomerulosclerosis (FSGS). The mechanisms by which TRPC6 mutations cause kidney disease are not well understo ... Full text Link to item Cite

Mesenchymal stem cells stimulate protective genetic reprogramming of injured cardiac ventricular myocytes.

Journal Article J Mol Cell Cardiol · February 2011 Since massive irreversible loss of cardiac myocytes occurs following myocardial injury, injection of human mesenchymal stem cells (hMSCs) has emerged as a promising therapeutic intervention. Despite the growing enthusiasm for this approach, the understandi ... Full text Link to item Cite

Regulating the regulator: NF-kappaB signaling in heart.

Journal Article J Mol Cell Cardiol · October 2006 The Nuclear Factor-kappaB (NF-kappaB) signaling pathway has been linked to several pathologic processes in the myocardium including cardiomyocyte proinflammatory cytokine release, ischemia/reperfusion injury, hypertrophy and apoptosis. However, very little ... Full text Link to item Cite

Pregnancy and estradiol modulate myometrial G-protein pathways in the guinea pig.

Journal Article Am J Obstet Gynecol · July 2006 OBJECTIVE: Coupled to hundreds of receptors, G-proteins modulate signal transduction pathways and are important hormonal targets. The first objective was to determine the effect of pregnancy and estradiol on myometrial guanosine triphosphatase activity. Th ... Full text Link to item Cite

Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma.

Journal Article J Exp Med · May 15, 2006 Emerging evidence suggests that both human stem cells and mature stromal cells can play an important role in the development and growth of human malignancies. In contrast to these tumor-promoting properties, we observed that in an in vivo model of Kaposi's ... Full text Link to item Cite

Inhibitor-kappaB kinase-beta regulates LPS-induced TNF-alpha production in cardiac myocytes through modulation of NF-kappaB p65 subunit phosphorylation.

Journal Article Am J Physiol Heart Circ Physiol · November 2005 TNF-alpha is recognized as a significant contributor to myocardial dysfunction. Although several studies suggest that members of the NF-kappaB family of transcription factors are essential regulators of myocardial TNF-alpha gene expression, recent developm ... Full text Link to item Cite

Endotoxin stress-response in cardiomyocytes: NF-kappaB activation and tumor necrosis factor-alpha expression.

Journal Article Am J Physiol Heart Circ Physiol · March 2002 Although tumor necrosis factor (TNF)-alpha is implicated in numerous cardiac pathologies, the intracellular events leading to its production by heart cells are largely unknown. The goal of the present study was to identify the role of the transcription fac ... Full text Link to item Cite

Pregnancy and estradiol decrease GTPase activity in the guinea pig uterine artery.

Journal Article Am J Physiol Heart Circ Physiol · November 2001 The mechanisms by which pregnancy redistributes cardiac output in an organ-specific manner are poorly understood. We propose that it is consequential to estrogen-mediated alterations in G protein-mediated signal transduction. Aortas and uterine (UAs) and m ... Full text Link to item Cite