About

David Bilder is a Professor of Cell Biology, Development and Physiology at the University of California, Berkeley. His research description can be found at http://mcb.berkeley.edu/faculty/CDB/bilderd.html, and his laboratory is located at 539 Weill Hall. He is involved in research within the Department of Molecular and Cell Biology, focusing on cell biology, development, and physiology. His contact information includes his email bilder@berkeley.edu, office phone (510) 642-8605, and lab phone (510) 642-8053. Additional details about his professional activities and contributions are available through the department's website.

Research topics

• Biology
• Cell biology
• Neuroscience
• Medicine
• Pathology
• Immunology
• Cancer research
• Biochemistry
• Genetics
• Computational biology

Selected publications

• Basement membrane patterning by spatial deployment of a secretion-regulating protease

  Proceedings of the National Academy of Sciences · 2025-05-13 · 5 citations

  articleOpen accessSenior authorCorresponding

  While paradigms for patterning of cell fates in development are well established, paradigms for patterning morphogenesis, particularly when organ shape is influenced by the extracellular matrix (ECM), are not. Morphogenesis of the Drosophila egg chamber (follicle) depends on anterior–posterior distribution of basement membrane (BM) components such as Collagen IV (Col4), whose gradient creates tissue mechanical properties that specify the degree of elongation. Here, we show that the gradient is not regulated by Col4 transcription but instead relies on posttranscriptional mechanisms. The metalloprotease ADAMTS-A, expressed in a gradient inverse to that of Col4, limits Col4 deposition in the follicle center and manipulation of its levels can cause either organ hyper- or hypoelongation. We present evidence that ADAMTS-A acts within the secretory pathway, rather than extracellularly, to limit Col4 incorporation into the BM. High levels of ADAMTS-A in follicle termini are normally dispensable but suppress Col4 incorporation when transcription is elevated. Meanwhile, the terminally expressed metalloprotease Stall increases Col4 turnover in the posterior. Our data show how an organ can employ patterned expression of ECM proteases with intracellular as well as extracellular activity to specify BM properties that control shape.

  PublisherDOI

• Fly wounds and tumors restrict macrophages via a matrix degradation-moderating protease inhibitor

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-15 · 1 citations

  preprintOpen accessSenior authorCorresponding

  ABSTRACT Breaches of epithelial homeostasis trigger an inflammatory response. Not only initiation but negative regulation of the response is critical, as autoinflammation can cause tissue damage and chronic disease. Epithelial breaches can be signaled by damage-associated molecular patterns (DAMPs), including basement membrane (BM) degradation, that attract inflammatory cells. Here we show that the conserved thioester-containing protein Tep3 from Drosophila limits innate immune cell attachment to damaged and transformed epithelia. Tep3 is produced in wounds and tumors alongside the matrix metalloprotease MMP1. Tep3 inhibits MMP1 proteolytic activity, reducing production of a BM DAMP that is necessary for macrophage association. A Drosophila tumor upregulates Tep3 to limit an MMP1- and macrophage-dependent anti-tumor immune response, thus accelerating progression and host death. Hence, fly tumors can exploit a physiological anti-inflammatory axis to pathologically limit their immune restriction.

  PublisherOA PDFDOI

• Advancing cancer research via comparative oncology

  Nature reviews. Cancer · 2025-06-27 · 8 citations

  reviewOpen access
  PublisherOA PDFDOI

• Beyond Mice and Men: Alternative Vertebrate and Invertebrate Models in Cancer Biology

  Annual Review of Cancer Biology · 2025-10-31

  article1st authorCorresponding

  While cancer looms large in the public and scientific minds, this can result in a quite narrow view of its range and manifestations. The centering of human clinical investigations and the popularity of mouse models leave many unaware of fascinating findings about cancer in other species. Comparative oncology shows that cancer can be found not just in mammals but widely across the tree of animals, a realization that broadens views of the disease in fundamentally important ways. Examples include protective mechanisms of cancer-resistant species, transmissible cancers, and questions about whether cancer risk is intrinsic to metazoan life. I highlight strong evidence for cancer in invertebrates, focusing on Drosophila , which not only show many hallmarks of cancer but also induce host responses mimicking those of human patients, including antitumor immunity. A wide-ranging study of cancer-bearing species enhances the potential for transformative advances in battling this ancient disease.

  PublisherDOI

• Paraneoplastic renal dysfunction in fly cancer models driven by inflammatory activation of stem cells

  Proceedings of the National Academy of Sciences · 2024-10-11 · 6 citations

  articleOpen accessCorresponding

  Tumors can induce systemic disturbances in distant organs, leading to physiological changes that enhance host morbidity. In Drosophila cancer models, tumors have been known for decades to cause hypervolemic "bloating" of the abdominal cavity. Here we use allograft and transgenic tumors to show that hosts display fluid retention associated with autonomously defective secretory capacity of fly renal tubules, which function analogous to those of the human kidney. Excretion from these organs is blocked by abnormal cells that originate from inappropriate activation of normally quiescent renal stem cells (RSCs). Blockage is initiated by IL-6-like oncokines that perturb renal water-transporting cells and trigger a damage response in RSCs that proceeds pathologically. Thus, a chronic inflammatory state produced by the tumor causes paraneoplastic fluid dysregulation by altering cellular homeostasis of host renal units.

  PublisherDOI

• Paraneoplastic renal dysfunction in fly cancer models driven by inflammatory activation of stem cells

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-03-25 · 3 citations

  preprintOpen accessCorresponding

  ABSTRACT Tumors can induce systemic disturbances in distant organs, leading to physiological changes that enhance host morbidity. In Drosophila cancer models, tumors have been known for decades to cause hypervolemic ‘bloating’ of the abdominal cavity. Here we use allograft and transgenic tumors to show that hosts display fluid retention associated with autonomously defective secretory capacity of fly renal tubules, which function analogous to those of the human kidney. Excretion from these organs is blocked by abnormal cells that originate from inappropriate activation of normally quiescent renal stem cells (RSCs). Blockage is initiated by IL-6-like oncokines that perturb renal water-transporting cells, and trigger a damage response in RSCs that proceeds pathologically. Thus, a chronic inflammatory state produced by the tumor causes paraneoplastic fluid dysregulation by altering cellular homeostasis of host renal units. Significance Statement Tumors cause pathophysiological changes to host tissues, including distant organs. Here we use fruit fly cancer models to uncover mechanisms underlying paraneoplastic renal dysfunction. IL-6-like signaling from the tumor induces inflammatory signaling in renal tubule cells. Defects in these cells are sensed by normally quiescent renal stem cells, leading to inappropriate proliferation in a damage-like response. Chronic activation in the tumor context results in physical obstruction of tubule ducts and thus failures in fluid clearance. This fly work can prompt investigation of analogous mechanisms underlying renal dysfunction in cancer patients.

  PublisherOA PDFDOI

• Basement membrane patterning by spatial deployment of a secretion-regulating protease

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-07-10 · 1 citations

  preprintOpen accessSenior authorCorresponding

  While paradigms for patterning of cell fates in development are well-established, paradigms for patterning morphogenesis, particularly when organ shape is influenced by the extracellular matrix (ECM), are less so. Morphogenesis of the Drosophila egg chamber (follicle) depends on anterior-posterior distribution of basement membrane (BM) components such as Collagen IV (Col4), whose symmetric gradient creates tissue mechanical properties that specify the degree of elongation. Here we show that the gradient is not regulated by Col4 transcription but instead relies on post-transcriptional mechanisms. The metalloprotease ADAMTS-A, expressed in a gradient inverse to that of Col4, limits Col4 deposition in the follicle center and manipulation of its levels can cause either organ hyper- or hypo-elongation. We present evidence that ADAMTS-A acts within the secretory pathway, rather than extracellularly, to limit Col4 incorporation into the BM. High levels of ADAMTS-A in follicle termini are normally dispensable but suppress Col4 incorporation when transcription is elevated. Our data show how an organ can employ patterned expression of ECM proteases with intracellular as well as extracellular activity to specify BM properties that control shape.

  PublisherOA PDFDOI

• Decision letter: Continuous muscle, glial, epithelial, neuronal, and hemocyte cell lines for Drosophila research

  2023-02-21

  peer-reviewOpen accessSenior author

  Fruit flies are widely used in the life and biomedical sciences as models of animal biology. They are small in size and easy to care for in a laboratory, making them ideal for studying how the body works. There are, however, some experiments that are difficult to perform on whole flies and it would be advantageous to use populations of fruit fly cells grown in the laboratory – known as cell cultures – instead. Unlike studies in humans and other mammals, which – for ethical and practical reasons –heavily rely on cell cultures, few studies have used fruit fly cell cultures. Recent work has shown that having an always active version of a gene called Ras in fruit fly cells helps the cells to survive and grow in cultures, making it simpler to generate new fruit fly cell lines compared with traditional methods. However, the methods used to express activated Ras result in cell lines that can be a mixture of many different types of cell, which limits how useful they are for research. Here, Coleman-Gosser, Hu, Raghuvanshi, Stitzinger et al. aimed to use Ras to generate a collection of cell lines from specific types of fruit fly cells in the muscle, nervous system, blood and other parts of the body. The experiments show that selectively expressing activated Ras in an individual type of cell enables them to outcompete other cells in culture to generate a cell line consisting only of the cell type of interest. The new cell lines offer models for experiments that more closely reflect their counterparts in flies. For example, the team were able to recapitulate how fly muscles develop by treating one of the cell lines with a hormone called ecdysone, which triggered the cells to mature into active muscle cells that spontaneously contract and relax. In the future, the new cell lines could be used for various experiments including high throughput genetic screening or testing the effects of new drugs and other compounds. The method used in this work may also be used by other researchers to generate more fruit fly cell lines.

  PublisherDOI

• Specialized cells that sense tissue mechanics to regulate Drosophila morphogenesis

  Developmental Cell · 2023-01-27 · 19 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Systemic coagulopathy promotes host lethality in a new Drosophila tumor model

  Current Biology · 2023-06-24 · 19 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

Recent grants

• NIH Grant R21CA180107

  NIH · $281k · 2016

• Shaping of simple organ by anisotropic biomechanical forces

  NIH · $1.2M · 2014–2019

• Epithelial biology: morphogenesis and damage signaling

  NIH · $6.5M · 2019–2029

• NIH Grant R01GM068675

  NIH · $3.9M · 2019

• Mechanisms of Drosophila Tumor Suppression

  NIH · $2.0M · 2010–2020

Frequent coauthors

• Norbert Perrimon

  Howard Hughes Medical Institute

  25 shared

• Thomas Vaccari

  University of Milan

  17 shared

• Tor Erik Rusten

  University of Oslo

  16 shared

• Harald Stenmark

  University of Oslo

  16 shared

• Christian Ghiglione

  Université Paris 8

  15 shared

• Laufey T. Ámundadóttir

  13 shared

• Yacine Graba

  Institut de Biologie du Développement Marseille

  12 shared

• Kermit L. Carraway

  9 shared