About

Karam Aboudehen, PhD, is an Assistant Professor of Medicine in the Division of Nephrology & Hypertension at the Renaissance School of Medicine, Stony Brook University. His research focuses on polycystic kidney disease (PKD), a genetic disorder characterized by cyst formation in the kidneys leading to end-stage renal disease. He studies long noncoding RNAs (lncRNAs) and their role in the pathogenesis of PKD, aiming to discover therapeutically targetable lncRNAs that can prevent or mitigate cyst formation and progression. Aboudehen has utilized multiple orthologous PKD mouse models to identify dysregulated lncRNAs during cystogenesis, such as Hoxb3os and Pvt1, which directly modulate cyst development. His work reveals that downregulation of Hoxb3os exacerbates cystogenesis by affecting mTOR signaling and cellular metabolism, while upregulation of Pvt1 promotes cyst progression by stabilizing c-MYC levels. His research employs cutting-edge technologies including mouse molecular genetics, next-generation sequencing, CRISPR/Cas9 gene editing, and viral gene delivery. Aboudehen's long-term goal is to develop novel therapeutic approaches targeting these lncRNAs to treat PKD.

Research topics

• Cell biology
• Cancer research
• Biology
• Genetics
• Medicine
• Pathology
• Endocrinology
• Molecular biology
• Immunology

Selected publications

• Loss of Snhg5 disrupts cell-cycle regulation without altering cystogenesis in a mouse model of polycystic kidney disease

  Scientific Reports · 2026-01-08

  articleOpen accessSenior authorCorresponding

  Long non-coding RNAs (lncRNAs) regulate diverse cellular pathways and are increasingly linked to human disease. Snhg5 is frequently described as a pathogenic lncRNA in many human diseases, including cancer. Our previous studies revealed that Snhg5 is one of the most upregulated lncRNAs in multiple mouse models of polycystic kidney disease (PKD). Yet its role in renal biology and in autosomal dominant PKD (ADPKD) is not known. To elucidate the role of Snhg5, we generated a global Snhg5-null mouse. Homozygous animals were viable and displayed normal kidney morphology and function. RNA-sequencing of Snhg5-null kidneys and renal epithelial cells revealed common alterations in gene expression linked to cell cycle progression and DNA replication. At the molecular level, Snhg5-null cells showed increased sub-G1 and S/G2/M fractions, coinciding with depletion of ARPC5-a core ARP2/3 subunit-suggesting that reduced ARPC5 may contribute to this phenotype. To determine whether Snhg5 upregulation is pathogenic in mouse PKD, we crossed Snhg5-null mice with a collecting duct-specific Pkd1-mutant mouse model. Loss of Snhg5 did not attenuate cyst formation; if anything, disease severity was mildly but not significantly exacerbated. These findings indicate that Snhg5 modulates cell-cycle control and is dispensable for kidney development and cystogenesis in collecting duct-derived cysts.

  PublisherOA PDFDOI

• An RNA transmethylation pathway governs kidney nephrogenic potential

  Nature Communications · 2025-05-28 · 1 citations

  articleOpen access

  The adult kidney lacks the ability to generate new nephrons, placing individuals born with low nephron counts at greater risk for chronic kidney disease as they age. Limited nutrient availability hinders nephron formation; however, the key metabolic dependencies remain unclear. Here we show that S-adenosylmethionine (SAM) and cellular transmethylation status are crucial determinants of the kidney’s nephrogenic capacity. The RNA methyltransferase METTL3 serves as a SAM sensor and is essential for the fate determination of nephron progenitor cells (NPCs). Reducing transmethylation or inhibiting METTL3 blocks NPC differentiation and nephrogenesis, whereas enhancing transmethylation or increasing METTL3 activity facilitates an induced NPC population and increases nephron production. Additionally, we identify Lrpprc mRNA, encoding a mitochondrially enriched protein, as a key direct target of METTL3-mediated transmethylation. Accordingly, inhibiting LRPPRC negates the nephrogenic effects of SAM and METTL3. Our findings reveal a modifiable methionine-SAM-RNA transmethylation pathway that can be targeted to enhance nephron formation. The mechanisms governing kidney nephrogenic capacity are incompletely understood. Here, the authors reveal that METTL3-dependent RNA transmethylation is both necessary and sufficient to promote nephron progenitor differentiation, and that targeting this pathway enhances murine nephron endowment.

  PublisherOA PDFDOI

• Evolving Understanding of RNA Biology in Kidney Disease

  Journal of the American Society of Nephrology · 2025-12-24

  articleOpen access
  PublisherOA PDFDOI

• Ablation of Long Noncoding RNA Hoxb3os Exacerbates Cystogenesis in Mouse Polycystic Kidney Disease

  Journal of the American Society of Nephrology · 2023 · 11 citations

  Senior authorCorresponding
  • Biology
  • Cancer research
  • Cell biology

  SIGNIFICANCE STATEMENT: Long noncoding RNAs (lncRNAs) are a class of nonprotein coding RNAs with pivotal functions in development and disease. They have emerged as an exciting new drug target category for many common conditions. However, the role of lncRNAs in autosomal dominant polycystic kidney disease (ADPKD) has been understudied. This study provides evidence implicating a lncRNA in the pathogenesis of ADPKD. We report that Hoxb3os is downregulated in ADPKD and regulates mammalian target of rapamycin (mTOR)/Akt pathway in the in vivo mouse kidney. Ablating the expression of Hoxb3os in mouse polycystic kidney disease (PKD) activated mTOR complex 2 (mTORC2) signaling and exacerbated the cystic phenotype. The results from our study provide genetic proof of concept for future studies that focus on targeting lncRNAs as a treatment option in PKD. BACKGROUND: ADPKD is a monogenic disorder characterized by the formation of kidney cysts and is primarily caused by mutations in two genes, PKD1 and PKD2 . METHODS: In this study, we investigated the role of lncRNA Hoxb3os in ADPKD by ablating its expression in the mouse. RESULTS: Hoxb3os -null mice were viable and had grossly normal kidney morphology but displayed activation of mTOR/Akt signaling and subsequent increase in kidney cell proliferation. To determine the role of Hoxb3os in cystogenesis, we crossed the Hoxb3os -null mouse to two orthologous Pkd1 mouse models: Pkhd1/Cre; Pkd1F/F (rapid cyst progression) and Pkd1RC/RC (slow cyst progression). Ablation of Hoxb3os exacerbated cyst growth in both models. To gain insight into the mechanism whereby Hoxb3os inhibition promotes cystogenesis, we performed western blot analysis of mTOR/Akt pathway between Pkd1 single-knockout and Pkd1 - Hoxb3os double-knockout (DKO) mice. Compared with single-knockout, DKO mice presented with enhanced levels of total and phosphorylated Rictor. This was accompanied by increased phosphorylation of Akt at Ser 473 , a known mTORC2 effector site. Physiologically, kidneys from DKO mice displayed between 50% and 60% increase in cell proliferation and cyst number. CONCLUSIONS: The results from this study indicate that ablation of Hoxb3os in mouse PKD exacerbates cystogenesis and dysregulates mTORC2.

  PublisherDOI

• Ablation of Long Noncoding RNA Hoxb3os Exacerbates Cystogenesis in Mouse Polycystic Kidney Disease

  Journal of the American Society of Nephrology · 2023-11-01

  article1st authorCorresponding
  PublisherDOI

• Self-Complementary Adeno-Associated Viral Gene Delivery in the Metanephric Organ Culture Identifies Pvt1 as Modulator of Cystogenesis

  Journal of the American Society of Nephrology · 2022-11-01

  article1st authorCorresponding

  Aboudehen, Karam S.; Eckberg, Kara; Weisser, Ivan D.; Buttram, Daniel J.; Somia, Nikunj; Igarashi, Peter Author Information

  PublisherDOI

• Small hairpin inhibitory RNA delivery in the metanephric organ culture identifies long noncoding RNA <i>Pvt1</i> as a modulator of cyst growth

  AJP Renal Physiology · 2022 · 8 citations

  Senior authorCorresponding
  • Biology
  • Cell biology
  • Molecular biology

  activity in autosomal dominant polycystic kidney disease might reduce cyst growth.

  PublisherOA PDFDOI

• Interstitial microRNA miR-214 attenuates inflammation and polycystic kidney disease progression

  JCI Insight · 2020 · 63 citations

  • Biology
  • Cancer research
  • Cell biology

  Renal cysts are the defining feature of autosomal dominant polycystic kidney disease (ADPKD); however, the substantial interstitial inflammation is an often-overlooked aspect of this disorder. Recent studies suggest that immune cells in the cyst microenvironment affect ADPKD progression. Here we report that microRNAs (miRNAs) are new molecular signals in this crosstalk. We found that miR-214 and its host long noncoding RNA Dnm3os are upregulated in orthologous ADPKD mouse models and cystic kidneys from humans with ADPKD. In situ hybridization revealed that interstitial cells in the cyst microenvironment are the primary source of miR-214. While genetic deletion of miR-214 does not affect kidney development or homeostasis, surprisingly, its inhibition in Pkd2- and Pkd1-mutant mice aggravates cyst growth. Mechanistically, the proinflammatory TLR4/IFN-γ/STAT1 pathways transactivate the miR-214 host gene. miR-214, in turn as a negative feedback loop, directly inhibits Tlr4. Accordingly, miR-214 deletion is associated with increased Tlr4 expression and enhanced pericystic macrophage accumulation. Thus, miR-214 upregulation is a compensatory protective response in the cyst microenvironment that restrains inflammation and cyst growth.

  PublisherOA PDFDOI

• Regulation of mTOR signaling by long non-coding RNA

  Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · 2019-11-18 · 30 citations

  reviewOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Mechanism of Fibrosis in HNF1B-Related Autosomal Dominant Tubulointerstitial Kidney Disease

  Journal of the American Society of Nephrology · 2018-08-10 · 102 citations

  articleOpen access

  Background Mutation of HNF1B , the gene encoding transcription factor HNF-1 β , is one cause of autosomal dominant tubulointerstitial kidney disease, a syndrome characterized by tubular cysts, renal fibrosis, and progressive decline in renal function. HNF-1 β has also been implicated in epithelial–mesenchymal transition (EMT) pathways, and sustained EMT is associated with tissue fibrosis. The mechanism whereby mutated HNF1B leads to tubulointerstitial fibrosis is not known. Methods To explore the mechanism of fibrosis, we created HNF-1 β –deficient mIMCD3 renal epithelial cells, used RNA-sequencing analysis to reveal differentially expressed genes in wild-type and HNF-1 β –deficient mIMCD3 cells, and performed cell lineage analysis in HNF-1 β mutant mice. Results The HNF-1 β –deficient cells exhibited properties characteristic of mesenchymal cells such as fibroblasts, including spindle-shaped morphology, loss of contact inhibition, and increased cell migration. These cells also showed upregulation of fibrosis and EMT pathways, including upregulation of Twist2, Snail1, Snail2, and Zeb2, which are key EMT transcription factors. Mechanistically, HNF-1 β directly represses Twist2 , and ablation of Twist2 partially rescued the fibroblastic phenotype of HNF-1 β mutant cells. Kidneys from HNF-1 β mutant mice showed increased expression of Twist2 and its downstream target Snai2 . Cell lineage analysis indicated that HNF-1 β mutant epithelial cells do not transdifferentiate into kidney myofibroblasts. Rather, HNF-1 β mutant epithelial cells secrete high levels of TGF- β ligands that activate downstream Smad transcription factors in renal interstitial cells. Conclusions Ablation of HNF-1 β in renal epithelial cells leads to the activation of a Twist2-dependent transcriptional network that induces EMT and aberrant TGF- β signaling, resulting in renal fibrosis through a cell-nonautonomous mechanism.

  PublisherOA PDFDOI

Recent grants

• Deregulation of Long Noncoding RNA in the Pathogenesis of Autosomal Dominant Polycystic Kidney Disease

  NIH · $544k · 2019–2025

Frequent coauthors

• Peter Igarashi

  Twin Cities Orthopedics

  17 shared

• Marco Pontoglio

  Centre National de la Recherche Scientifique

  12 shared

• Robert R. Kraemer

  Southeastern Louisiana University

  11 shared

• Vishal Patel

  Dharmsinh Desai University

  11 shared

• Edmund O. Acevedo

  Bridge University

  10 shared

• V. Daniel Castracane

  10 shared

• Edward Hébert

  Southeastern Louisiana University

  10 shared

• Daniel Hollander

  10 shared

Awards & honors

• K01DK116934-02 Aboudehen (PI)
• R01DK42921: Igarashi (PI and mentor), Aboudehen (Co-PI)
• REG-217886-01 Aboudehen (PI)