All Publications

  • Healthcare-Associated Clostridioides difficile Infection: Learning the Perspectives of Healthcare Workers to Build Successful Strategies. American journal of infection control Lev, V., Anbarchian, T., Yao, H., Bhat, A., Britt, P., Shieh, L. 2023


    BACKGROUND: Clostridioides difficile (C. difficile) is one of the most common healthcare-associated infections that negatively impacts patient care and healthcare costs. This study takes a unique approach to C. difficile infection (CDI) control by investigating key prevention obstacles through the perspectives of Stanford Health Care (SHC) frontline healthcare personnel.METHODS: An anonymous qualitative survey was distributed at SHC, focusing on knowledge and practice of CDI prevention guidelines, as well as education, communication, and perspectives regarding CDI at SHC.RESULTS: 112 survey responses were analyzed. Our findings unveiled gaps in personnel's knowledge of C. difficile diagnostic guidelines, and revealed a need for targeted communication and guideline-focused education. Healthcare staff shared preferences and recommendations, with the majority recommending enhanced communication of guidelines and information as a strategy for reducing CDI rates. The findings were then used to design and propose internal recommendations for SHC to mitigate the gaps found.DISCUSSION: Many guidelines and improvement strategies are based on strong scientific and medical foundations; however, it is important to ask whether these guidelines are effectively translated into practice. Frontline healthcare workers hold empirical perspectives that could be key in infection control.CONCLUSIONS: Our findings emphasize the importance of including frontline healthcare personnel in infection prevention decision-making processes and the strategies presented here can be applied to mitigating infections in different healthcare settings.

    View details for DOI 10.1016/j.ajic.2023.08.008

    View details for PubMedID 37579972

  • Intermittent fasting induces rapid hepatocyte proliferation to restore the hepatostat in the mouse liver. eLife Sarkar, A., Jin, Y., DeFelice, B. C., Logan, C. Y., Yang, Y., Anbarchian, T., Wu, P., Morri, M., Neff, N. F., Nguyen, H., Rulifson, E., Fish, M., Kaye, A. G., Martínez Jaimes, A. M., Nusse, R. 2023; 12


    Nutrient availability fluctuates in most natural populations, forcing organisms to undergo periods of fasting and re-feeding. It is unknown how dietary changes influence liver homeostasis. Here, we show that a switch from ad libitum feeding to intermittent fasting (IF) promotes rapid hepatocyte proliferation. Mechanistically, IF-induced hepatocyte proliferation is driven by the combined action of systemic FGF15 and localized WNT signaling. Hepatocyte proliferation during periods of fasting and re-feeding re-establishes a constant liver-to-body mass ratio, thus maintaining the hepatostat. This study provides the first example of dietary influence on adult hepatocyte proliferation and challenges the widely held view that liver tissue is mostly quiescent unless chemically or mechanically injured.

    View details for DOI 10.7554/eLife.82311

    View details for PubMedID 36719070

    View details for PubMedCentralID PMC9889086

  • Assessment of Hepatocyte Ploidy by Flow Cytometry. Methods in molecular biology (Clifton, N.J.) Jin, Y., Anbarchian, T., Nusse, R. 2022; 2544: 171-181


    Polyploidy is a common and dynamic feature of mature rodent and human hepatocytes. While polyploidization occurs naturally during growth, alterations in the distribution of diploid and polyploid cells in the liver can be indicative of tissue stress or a pathologic state. Here, we describe a method for flow cytometric quantification of ploidy distribution by staining with propidium iodide. We first outline a hepatocyte isolation procedure from mouse liver through a two-step perfusion system for analysis of cellular ploidy. In an alternative approach, we employ a nuclei isolation protocol to assess nuclear ploidy. Finally, we describe how the use of fluorescent cell markers is compatible with these methods and helps retain information on cellular position within the tissue.

    View details for DOI 10.1007/978-1-0716-2557-6_12

    View details for PubMedID 36125718

  • Wnt signaling regulates hepatocyte cell division by a transcriptional repressor cascade Wnt signaling regulates hepatocyte cell division by a transcriptional repressor cascade Jin, Y., Anbarchian, T., Wu, P., Sarkar, A., Fish, M., Peng, W., Nusse, R. 2022

    View details for DOI 10.1073/pnas.2203849119

  • Inflammatory Cytokine TNF alpha Promotes the Long-Term Expansion of Primary Hepatocytes in 3D Culture CELL Peng, W., Logan, C. Y., Fish, M., Anbarchian, T., Aguisanda, F., Alvarez-Varela, A., Wu, P., Jin, Y., Zhu, J., Li, B., Grompe, M., Wang, B., Nusse, R. 2018; 175 (6): 1607-+
  • Wnt/beta-catenin signaling regulates ependymal cell development and adult homeostasis PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Xing, L., Anbarchian, T., Tsai, J. M., Plant, G. W., Nusse, R. 2018; 115 (26): E5954–E5962
  • Smad2 and Smad3 Regulate Chondrocyte Proliferation and Differentiation in the Growth Plate PLOS GENETICS Wang, W., Song, B., Anbarchian, T., Shirazyan, A., Sadik, J. E., Lyons, K. M. 2016; 12 (10)


    TGFβs act through canonical and non-canonical pathways, and canonical signals are transduced via Smad2 and Smad3. However, the contribution of canonical vs. non-canonical pathways in cartilage is unknown because the role of Smad2 in chondrogenesis has not been investigated in vivo. Therefore, we analyzed mice in which Smad2 is deleted in cartilage (Smad2CKO), global Smad3-/- mutants, and crosses of these strains. Growth plates at birth from all mutant strains exhibited expanded columnar and hypertrophic zones, linked to increased proliferation in resting chondrocytes. Defects were more severe in Smad2CKO and Smad2CKO;Smad3-/- (Smad2/3) mutant mice than in Smad3-/- mice, demonstrating that Smad2 plays a role in chondrogenesis. Increased levels of Ihh RNA, a key regulator of chondrocyte proliferation and differentiation, were seen in prehypertrophic chondrocytes in the three mutant strains at birth. In accordance, TGFβ treatment decreased Ihh RNA levels in primary chondrocytes from control (Smad2fx/fx) mice, but inhibition was impaired in cells from mutants. Consistent with the skeletal phenotype, the impact on TGFβ-mediated inhibition of Ihh RNA expression was more severe in Smad2CKO than in Smad3-/- cells. Putative Smad2/3 binding elements (SBEs) were identified in the proximal Ihh promoter. Mutagenesis demonstrated a role for three of them. ChIP analysis suggested that Smad2 and Smad3 have different affinities for these SBEs, and that the repressors SnoN and Ski were differentially recruited by Smad2 and Smad3, respectively. Furthermore, nuclear localization of the repressor Hdac4 was decreased in growth plates of Smad2CKO and double mutant mice. TGFβ induced association of Hdac4 with Smad2, but not with Smad3, on the Ihh promoter. Overall, these studies revealed that Smad2 plays an essential role in the development of the growth plate, that both Smads 2 and 3 inhibit Ihh expression in the neonatal growth plate, and suggested they accomplish this by binding to distinct SBEs, mediating assembly of distinct repressive complexes.

    View details for DOI 10.1371/journal.pgen.1006352

    View details for Web of Science ID 000386683300020

    View details for PubMedID 27741240

    View details for PubMedCentralID PMC5065210

  • Mining the phytomicrobiome to understand how bacterial coinoculations enhance plant growth FRONTIERS IN PLANT SCIENCE Maymon, M., Martinez-Hidalgo, P., Tran, S. S., Ice, T., Craemer, K., Anbarchian, T., Sung, T., Hwang, L. H., Chou, M., Fujishige, N. A., Villella, W., Ventosa, J., Sikorski, J., Sanders, E. R., Faull, K. F., Hirsch, A. M. 2015; 6: 784


    In previous work, we showed that coinoculating Rhizobium leguminosarum bv. viciae 128C53 and Bacillus simplex 30N-5 onto Pisum sativum L. roots resulted in better nodulation and increased plant growth. We now expand this research to include another alpha-rhizobial species as well as a beta-rhizobium, Burkholderia tuberum STM678. We first determined whether the rhizobia were compatible with B. simplex 30N-5 by cross-streaking experiments, and then Medicago truncatula and Melilotus alba were coinoculated with B. simplex 30N-5 and Sinorhizobium (Ensifer) meliloti to determine the effects on plant growth. Similarly, B. simplex 30N-5 and Bu. tuberum STM678 were coinoculated onto Macroptilium atropurpureum. The exact mechanisms whereby coinoculation results in increased plant growth are incompletely understood, but the synthesis of phytohormones and siderophores, the improved solubilization of inorganic nutrients, and the production of antimicrobial compounds are likely possibilities. Because B. simplex 30N-5 is not widely recognized as a Plant Growth Promoting Bacterial (PGPB) species, after sequencing its genome, we searched for genes proposed to promote plant growth, and then compared these sequences with those from several well studied PGPB species. In addition to genes involved in phytohormone synthesis, we detected genes important for the production of volatiles, polyamines, and antimicrobial peptides as well as genes for such plant growth-promoting traits as phosphate solubilization and siderophore production. Experimental evidence is presented to show that some of these traits, such as polyamine synthesis, are functional in B. simplex 30N-5, whereas others, e.g., auxin production, are not.

    View details for DOI 10.3389/fpls.2015.00784

    View details for Web of Science ID 000443553400001

    View details for PubMedID 26442090

    View details for PubMedCentralID PMC4585168

  • The Type I BMP Receptor ACVR1/ALK2 is Required for Chondrogenesis During Development JOURNAL OF BONE AND MINERAL RESEARCH Rigueur, D., Brugger, S., Anbarchian, T., Kim, J., Lee, Y., Lyons, K. M. 2015; 30 (4): 733-741


    Bone morphogenetic proteins (BMPs) are crucial regulators of chondrogenesis. BMPs transduce their signals through three type I receptors: BMPR1A, BMPR1B, and ACVR1/ALK2. Fibrodysplasia ossificans progressiva (FOP), a rare disorder characterized by progressive ossification of connective tissue, is caused by an activating mutation in Acvr1 (the gene that encodes ACVR1/ALK2). However, there are few developmental defects associated with FOP. Thus, the role of ACVR1 in chondrogenesis during development is unknown. Here we report the phenotype of mice lacking ACVR1 in cartilage. Acvr1(CKO) mice are viable but exhibit defects in the development of cranial and axial structures. Mutants exhibit a shortened cranial base, and cervical vertebrae are hypoplastic. Acvr1(CKO) adult mice develop progressive kyphosis. These morphological defects were associated with decreased levels of Smad1/5 and p38 activation, and with reduced rates of chondrocyte proliferation in vertebral cartilage. We also tested whether ACVR1 exerts coordinated functions with BMPR1A and BMPR1B through analysis of double mutants. Acvr1/Bmpr1a and Acvr1/Bmpr1b mutant mice exhibited generalized perinatal lethal chondrodysplasia that was much more severe than in any of the corresponding mutant strains. These findings demonstrate that ACVR1 is required for chondrocyte proliferation and differentiation, particularly in craniofacial and axial elements, but exerts coordinated functions with both BMPR1A and BMPR1B throughout the developing endochondral skeleton.

    View details for DOI 10.1002/jbmr.2385

    View details for Web of Science ID 000352104400019

    View details for PubMedID 25413979

    View details for PubMedCentralID PMC4376569