About

Professor Greg Beitel leads the Beitel Laboratory within the Molecular Biosciences department at Northwestern University. His lab focuses on understanding how cells create complex three-dimensional organs by coordinately regulating their shapes with other cells. The primary model system used in his research is the Drosophila tracheal system, which serves as a genetically accessible model for organs such as the kidney, vascular system, and lung that are composed of tubular epithelial structures. Despite the critical importance of these organs, the fundamental molecular mechanisms underlying tubulogenesis and tube-size control remain poorly understood. Furthermore, there are currently no treatments for devastating diseases such as Polycystic Kidney Disease (PKD) that affect tube architecture. To address these challenges, Professor Beitel's lab employs genetic, molecular, cell biological, and biochemical approaches to investigate how the sizes of tracheal tubes are controlled. Additionally, his research probes the roles of vertebrate homologs of tracheal morphogenesis genes, aiming to shed light on conserved mechanisms of organ development and disease.

Research topics

• Biology
• Genetics
• Immunology
• Cell biology
• Computational biology
• Medicine
• Virology
• Internal medicine

Selected publications

• Myeloid Zfhx3 deficiency protects against hypercapnia-induced suppression of host defense against influenza A virus

  JCI Insight · 2024-01-16 · 9 citations

  articleOpen access

  Hypercapnia, elevation of the partial pressure of CO2 in blood and tissues, is a risk factor for mortality in patients with severe acute and chronic lung diseases. We previously showed that hypercapnia inhibits multiple macrophage and neutrophil antimicrobial functions and that elevated CO2 increases the mortality of bacterial and viral pneumonia in mice. Here, we show that normoxic hypercapnia downregulates innate immune and antiviral gene programs in alveolar macrophages (AMØs). We also show that zinc finger homeobox 3 (Zfhx3) - a mammalian ortholog of zfh2, which mediates hypercapnic immune suppression in Drosophila - is expressed in mouse and human macrophages. Deletion of Zfhx3 in the myeloid lineage blocked the suppressive effect of hypercapnia on immune gene expression in AMØs and decreased viral replication, inflammatory lung injury, and mortality in hypercapnic mice infected with influenza A virus. To our knowledge, our results establish Zfhx3 as the first known mammalian mediator of CO2 effects on immune gene expression and lay the basis for future studies to identify therapeutic targets to interrupt hypercapnic immunosuppression in patients with advanced lung disease.

  PublisherOA PDFDOI

• Myeloid <i>Zfhx3</i> Deficiency Protects Against Hypercapnia-induced Suppression of Host Defense Against Influenza A Virus

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-03-01 · 2 citations

  preprintOpen access

  Summary Hypercapnia, elevation of the partial pressure of CO 2 in blood and tissues, is a risk factor for mortality in patients with severe acute and chronic lung diseases. We previously showed that hypercapnia inhibits multiple macrophage and neutrophil antimicrobial functions, and that elevated CO 2 increases the mortality of bacterial and viral pneumonia in mice. Here, we show that normoxic hypercapnia downregulates innate immune and antiviral gene programs in alveolar macrophages (AMØs). We also show that zinc finger homeobox 3 (Zfhx3), mammalian ortholog of zfh2, which mediates hypercapnic immune suppression in Drosophila , is expressed in mouse and human MØs. Deletion of Zfhx3 in the myeloid lineage blocked the suppressive effect of hypercapnia on immune gene expression in AMØs and decreased viral replication, inflammatory lung injury and mortality in hypercapnic mice infected with influenza A virus. Our results establish Zfhx3 as the first known mammalian mediator of CO 2 effects on immune gene expression and lay the basis for future studies to identify therapeutic targets to interrupt hypercapnic immunosuppression in patients with advanced lung diseases. Graphical abstract

  PublisherOA PDFDOI

• Peer Review #2 of "A docked mutation phenocopies dumpy oblique alleles via altered vesicle trafficking (v0.1)"

  2021-10-13

  peer-reviewOpen access1st authorCorresponding

  The Drosophila extracellular matrix protein Dumpy (Dpy) is one of the largest proteins encoded by any animal.One class of dpy mutations produces a characteristic shortening of the wing blade known as oblique (dpy o ), due to altered tension in the developing wing.We describe here the characterization of docked (doc), a gene originally named because of an allele producing a truncated wing.We show that doc corresponds to the gene model CG5484, which encodes a homolog of the yeast protein Yif1 and plays a key role in ER to Golgi vesicle transport.Genetic analysis is consistent with a similar role for Doc in vesicle trafficking: docked alleles interact not only with genes encoding the COPII core proteins sec23 and sec13, but also with the SNARE proteins synaptobrevin and syntaxin.Further, we demonstrate that the strong similarity between the doc 1 and dpy o wing phenotypes reflects a functional connection between the two genes; we found that various dpy alleles are sensitive to changes in dosage of genes encoding other vesicle transport components such as sec13 and sar1.Doc's effects on trafficking are not limited to Dpy; for example, reduced doc dosage disturbed Notch pathway signaling during wing blade and vein development.These results suggest a model in which the oblique wing phenotype in doc 1 results from reduced transport of wild-type Dumpy protein; by extension, an additional implication is that the dpy o alleles can themselves be explained as hypomorphs.

  PublisherDOI

• Organ remodeling: The molecular choreography of a dance of destruction

  Current Biology · 2021-12-01 · 1 citations

  letterOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Mouse_transcrpts from Hypercapnia selectively modulates LPS-induced changes in innate immune and DNA replication-related gene transcription in the macrophage

  Figshare · 2021-01-01

  datasetOpen access

  Mouse microarray data

  PublisherDOI

• Human_Transcripts from Hypercapnia selectively modulates LPS-induced changes in innate immune and DNA replication-related gene transcription in the macrophage

  Figshare · 2021-01-01

  datasetOpen access

  Human microarray data

  PublisherDOI

• Decision letter: Duox-generated reactive oxygen species activate ATR/Chk1 to induce G2 arrest in Drosophila tracheoblasts

  2021-05-17

  peer-reviewOpen access
  PublisherDOI

• Hypercapnia selectively modulates LPS-induced changes in innate immune and DNA replication-related gene transcription in the macrophage

  Interface Focus · 2021 · 14 citations

  • Immunology
  • Biology
  • Cell biology

  -induced changes in macrophage gene expression help explain hypercapnic suppression of antibacterial and antiviral host defence in mice and reveal a mechanism that may underlie, at least in part, the high mortality of patients with severe lung disease and hypercapnia.

  PublisherOA PDFDOI

• Decision letter: Multiple Wnts act synergistically to induce Chk1/Grapes expression and mediate G2 arrest in Drosophila tracheoblasts

  2020-05-29

  peer-reviewOpen accessSenior author
  PublisherDOI

• Zfhx3 Mediates Hypercapnia-Induced Changes in Global Gene Transcription in Murine Alveolar Macrophages

  2020-05-01

  articleOpen access
  PublisherOA PDFDOI

Recent grants

• NIH Grant R01GM069540

  NIH · $1.3M · 2010

• Tube size control by Src and Yorkie/YAP

  NIH · $1.2M · 2014–2019

• Genes Mediating Innate Immune Suppression by Hypercapnia in Mammals and Flies

  NIH · $1.5M · 2011–2016

Frequent coauthors

• Peter H. S. Sporn

  Northwestern University

  26 shared

• Aisha Nair

  Northwestern University

  12 shared

• Sarah Paul

  All India Institute of Medical Sciences

  12 shared

• S. Marina Casalino‐Matsuda

  Northwestern University

  11 shared

• Jacob I. Sznajder

  Northwestern University

  10 shared

• H. Robert Horvitz

  McGovern Institute for Brain Research

  10 shared

• G. R. Scott Budinger

  Northwestern University

  9 shared

• Khalilah L. Gates

  Northwestern University

  8 shared

Education

• Ph.D.

  Massachusetts Institute of Technology

  1994

Awards & honors

• Helen Hay Whitney Postdoctoral Fellowship
• Burroughs Wellcome Career Development Award
• NSF CAREER Award