Welcome to Laboratory Investigation

Advancing the understanding of human and experimental disease


  • Visualization of segmented steatosis droplets

    Biology has evolved greatly in the past decade as high-throughput technologies were developed and applied to various biological disciplines. These technologies have generated an unprecedented amount and new types of biological data and how to make sense of “big data” is an emerging technological and conceptual challenge.

  • Immunofluorescent staining of human melanocytic specimens

    This Collection highlights the newest top-viewed content from Laboratory Investigation. Updated each month, we hope you enjoy reading this selection of articles. Laboratory Investigation aims to publish high-quality original research in all biomedical disciplines relating to the understanding of human disease and the application of new methods to the diagnosis of disease.

  • Pseudo-color rendering of fluorescence-like representations of non-small cell lung cancer

    Brightfield microscopy is the preferred method of pathologists for diagnosing solid tumors, utilizing common staining techniques such as hematoxylin and eosin staining and immunohistochemistry. This collection of articles describe new ways to process samples and interpret data generated by histopathology and immunohistochemistry, as well as new technologies that complement these methods.

  • Immunofluorescent staining of a mouse cardiac section with lectins

    The editors of Laboratory Investigation present a collection of recent papers that explore the relationships between changes in the mammalian glycome and pathobiology. These studies describe new roles for glycans in heart disease, neurodegenerative diseases, genetic disorders, and several types of cancer.

Laboratory Investigation is a Transformative Journal; authors can publish using the traditional publishing route OR via immediate gold Open Access.

Our Open Access option complies with funder and institutional requirements.


  • Mother-to-child transmission is the major cause of chronic hepatitis B virus (HBV) infection. This study shows that an unconventional protein secretion pathway that depends on autophagy may be hijacked by HBV to complete the process of intracellular transport. In HBV-infected trophoblasts, AnxA2-S100A10-mediated exocytosis may result in HBV intrauterine transmission.

    • Xiaoxia Bai
    • Jinshi Ran
    • Yongmei Xi
    Article Open Access
  • Pharmacological inhibition of the serine synthesis pathway with a highly selective inhibitor NCT503 synergistically works with temozolomide in inhibiting O6-methylguanine DNA methyltransferase (MGMT)-positive glioblastoma cell growth and inducing apoptosis both in vitro and in vivo. Mechanistically, NCT503 treatment reduces MGMT expression possibly via Wnt/βcatenin pathway. Reactive oxygen species-mediated DNA damage is at least partially involved. Combinational administration of NCT503 and TMZ may represent a novel and promising treatment strategy to enhance TMZ efficacy in patients with MGMT-high glioblastoma.

    • Lei Jin
    • Karrie Mei-Yee Kiang
    • Gilberto Ka-Kit Leung
  • Adrenomedullin (ADM) significantly stimulates osteoclastogenesis only in the presence of calcitonin. Functional ADM receptor partly composed of osteoclast-specific cell surface Kat1 antigen was detected in cells in the osteoclast-lineage. Expression of ADM receptor was firstly detected in proliferating osteoclast progenitors performing asymmetric cell division and is then expressed in mononuclear osteoclast precursors. Specific regulation of ADM receptors expressed on mononuclear osteoclast precursors could provide an alternative way to modulate bone remodeling therapeutically.

    • Toshio Kukita
    • Hidenobu Hiura
    • Akiko Kukita
  • The prevalence and contribution of viruses to heart failure phenotypes are increasingly recognized, while still underappreciated and underreported. We designed a tissue microarray with cardiac muscle tissue from 78 heart failure patients and probed for common cardiotropic viruses via in situ hybridization. Viral RNA was detected in 46.4% of patients, higher than anticipated for these heart failure conditions that include those not previously associated with a viral trigger or an exacerbating role.

    • Paul J. Hanson
    • Felicia Liu-Fei
    • Bruce M. McManus
  • This report provides new evidence supporting the role of ATP synthase inhibitory factor subunit 1 (IF1), an endogenous ATP synthase inhibitory protein, in regulating β-cell function. Investigations on genetic mouse models and an β-cell line indicate that IF1 negatively regulates cellular respiration and mitochondrial homeostasis, thus controlling insulin storage and release from islets.

    • Kailiang Zhang
    • Rong Bao
    • Qinglin Yang
  • The authors developed a deep convolutional neural network-based algorithm to support pathological muscle diagnosis. The algorithm differentiated idiopathic inflammatory myopathies and outperformed nine human physicians under limited diseases and conditions. These results suggest that the algorithm has the potential to be used directly in clinical settings.

    • Yoshinori Kabeya
    • Mariko Okubo
    • Ichizo Nishino
  • It is unclear how to best classify cancer outcomes using ‘omic data. We developed a multimetric feature-selection based multinomial logistic regression model that outperformed random forest models in classifying 4-category outcome of colorectal cancer. Adding microsatellite instability and oncogenic-driver data to clinical and transcriptomic data improves models’ performances, with pathologic staging, HBS1L, TSPYL4, and TP53TG3B as important features. Interestingly, precision and recall of tuned algorithms change as the feature number changes, but accuracy does not.

    • Catherine H. Feng
    • Mary L. Disis
    • Lanjing Zhang
  • Extensive morphological analysis demonstrates the importance of tunneling nanotubes for intercellular communication in osteoclast differentiation, especially in the fusion process of osteoclast precursors. Successful detection of nanotubes was also demonstrated in cultured primary osteoclasts resorbing dentin slices, and in osteoclasts in bone destruction sites of arthritic rats. Tunneling nanotubes are important for the differentiation of osteoclasts, both in vitro and in vivo.

    • Jing-Qi Zhang
    • Akira Takahashi
    • Toshio Kukita