My research interests are to develop a novel intestinal organoid model to study various pathogens and diseases, such as SARS-CoV-2, and inflammatory bowel disease.

Honors & Awards

  • MCHRI Fellow, Stanford Maternal and Child Health Research Institute (January 01 2022)

Professional Education

  • Master of Science, Youngstown State University (2016)
  • Doctor of Philosophy, University of British Columbia (2021)
  • Ph.D, University of British Columbia, Experimental Medicine (2021)

Stanford Advisors

All Publications

  • Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection Enhances Adaptive Immunity to C difficile Toxin B GASTROENTEROLOGY Cook, L., Rees, W. D., Wong, M. Q., Peters, H., Levings, M. K., Steiner, T. S. 2021; 160 (6): 2155-+

    View details for DOI 10.1053/j.gastro.2021.01.009

    View details for Web of Science ID 000646029700036

    View details for PubMedID 33444574

  • Recurrent Clostridioides difficile Infection Is Associated With Impaired T Helper Type 17 Immunity to C difficile Toxin B GASTROENTEROLOGY Cook, L., Rees, W. D., Wong, M. Q., Kwok, W. W., Levings, M. K., Steiner, T. S. 2021; 160 (4): 1410-+

    View details for DOI 10.1053/j.gastro.2020.11.043

    View details for Web of Science ID 000627499000058

    View details for PubMedID 33253683

  • A novel highly potent inhibitor of TMPRSS2-like proteases blocks SARS-CoV-2 variants of concern and is broadly protective against infection and mortality in mice. bioRxiv : the preprint server for biology Shapira, T., Monreal, I. A., Dion, S. P., Jager, M., Désilets, A., Olmstead, A. D., Vandal, T., Buchholz, D. W., Imbiakha, B., Gao, G., Chin, A., Rees, W. D., Steiner, T., Nabi, I. R., Marsault, E., Sahler, J., August, A., Van de Walle, G., Whittaker, G. R., Boudreault, P. L., Aguilar, H. C., Leduc, R., Jean, F. 2021


    The COVID-19 pandemic caused by the SARS-CoV-2 virus remains a global public health crisis. Although widespread vaccination campaigns are underway, their efficacy is reduced against emerging variants of concern (VOCs) 1,2 . Development of host-directed therapeutics and prophylactics could limit such resistance and offer urgently needed protection against VOCs 3,4 . Attractive pharmacological targets to impede viral entry include type-II transmembrane serine proteases (TTSPs), such as TMPRSS2, whose essential role in the virus lifecycle is responsible for the cleavage and priming of the viral spike protein 5-7 . Here, we identify and characterize a small-molecule compound, N-0385, as the most potent inhibitor of TMPRSS2 reported to date. N-0385 exhibited low nanomolar potency and a selectivity index of >10 6 at inhibiting SARS-CoV-2 infection in human lung cells and in donor-derived colonoids 8 . Importantly, N-0385 acted as a broad-spectrum coronavirus inhibitor of two SARS-CoV-2 VOCs, B.1.1.7 and B.1.351. Strikingly, single daily intranasal administration of N-0385 early in infection significantly improved weight loss and clinical outcomes, and yielded 100% survival in the severe K18-human ACE2 transgenic mouse model of SARS-CoV-2 disease. This demonstrates that TTSP-mediated proteolytic maturation of spike is critical for SARS-CoV-2 infection in vivo and suggests that N-0385 provides a novel effective early treatment option against COVID-19 and emerging SARS-CoV-2 VOCs.

    View details for DOI 10.1101/2021.05.03.442520

    View details for PubMedID 33972944

    View details for PubMedCentralID PMC8109206

  • Regenerative Intestinal Stem Cells Induced by Acute and Chronic Injury: The Saving Grace of the Epithelium? FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY Rees, W. D., Tandun, R., Yau, E., Zachos, N. C., Steiner, T. S. 2020; 8: 583919


    The intestinal epithelium is replenished every 3-4 days through an orderly process that maintains important secretory and absorptive functions while preserving a continuous mucosal barrier. Intestinal epithelial cells (IECs) derive from a stable population of intestinal stem cells (ISCs) that reside in the basal crypts. When intestinal injury reaches the crypts and damages IECs, a mechanism to replace them is needed. Recent research has highlighted the existence of distinct populations of acute and chronic damage-associated ISCs and their roles in maintaining homeostasis in several intestinal perturbation models. What remains unknown is how the damage-associated regenerative ISC population functions in the setting of chronic inflammation, as opposed to acute injury. What long-term consequences result from persistent inflammation and other cellular insults to the ISC niche? What particular "regenerative" cell types provide the most efficacious restorative properties? Which differentiated IECs maintain the ability to de-differentiate and restore the ISC niche? This review will cover the latest research on damage-associated regenerative ISCs and epigenetic factors that determine ISC fate, as well as provide opinions on future studies that need to be undertaken to understand the repercussions of the emergence of these cells, their contribution to relapses in inflammatory bowel disease, and their potential use in therapeutics for chronic intestinal diseases.

    View details for DOI 10.3389/fcell.2020.583919

    View details for Web of Science ID 000592227800001

    View details for PubMedID 33282867

    View details for PubMedCentralID PMC7688923

  • Enteroids Derived From Inflammatory Bowel Disease Patients Display Dysregulated Endoplasmic Reticulum Stress Pathways, Leading to Differential Inflammatory Responses and Dendritic Cell Maturation JOURNAL OF CROHNS & COLITIS Rees, W. D., Stahl, M., Jacobson, K., Bressler, B., Sly, L. M., Vallance, B. A., Steiner, T. S. 2020; 14 (7): 948-961


    Endoplasmic reticulum [ER] stress in intestinal epithelial cells [IECs] contributes to the pathogenesis of inflammatory bowel disease [IBD]. We hypothesized that ER stress changes innate signalling in human IECs, augmenting toll-like receptor [TLR] responses and inducing pro-inflammatory changes in underlying dendritic cells [DCs].Caco-2 cells and primary human colon-derived enteroid monolayers were exposed to ATP [control stressor] or thapsigargin [Tg] [ER stress inducer], and were stimulated with the TLR5 agonist flagellin. Cytokine release was measured by an enzyme immunoassay. ER stress markers CHOP, GRP78 and XBP1s/u were measured via quantitative PCR and Western blot. Monocyte-derived DCs [moDCs] were cultured with the IEC supernatants and their activation state was measured. Responses from enteroids derived from IBD patients and healthy control participants were compared.ER stress enhanced flagellin-induced IL-8 release from Caco-2 cells and enteroids. Moreover, conditioned media activated DCs to become pro-inflammatory, with increased expression of CD80, CD86, MHCII, IL-6, IL-15 and IL-12p70 and decreased expression of CD103 and IL-10. Flagellin-induced IL-8 production correlated with DC activation, suggesting a common stress pathway. Moreover, there were distinct differences in cytokine expression and basal ER stress between IBD and healthy subject-derived enteroid monolayers, suggesting a dysregulated ER stress pathway in IBD-derived enteroids.Cellular stress enhances TLR5 responses in IECs, leading to increased DC activation, indicating a previously unknown mechanistic link between epithelial ER stress and immune activation in IBD. Furthermore, dysregulated ER stress may be propagated from the intestinal epithelial stem cell niche in IBD patients.

    View details for DOI 10.1093/ecco-jcc/jjz194

    View details for Web of Science ID 000582311700010

    View details for PubMedID 31796949

  • How do immune and mesenchymal cells influence the intestinal epithelial cell compartment in inflammatory bowel disease? Let's crosstalk about it! JOURNAL OF LEUKOCYTE BIOLOGY Rees, W. D., Sly, L. M., Steiner, T. S. 2020; 108 (1): 309-321


    Intestinal epithelial cells provide a front line of defense by establishing a barrier against food Ags, pathogens, and commensal microorganisms. This defense includes the establishment of a tolerogenic environment in the gastrointestinal (GI) tract. The intestinal epithelium replenishes itself by cell turnover every 4-5 days, and this process is facilitated by various pathways of communication between the intestinal epithelial cells (IECs), the underlying stromal cell network, and professional immune cells, which together help establish a proper intestinal stem cell (ISC) niche in the crypt. However, during a state of inflammation, such as in inflammatory bowel diseases (IBD), these communication pathways can be altered, and this can lead to the development of inflammatory IECs within the crypt that further drive inflammation. Here, we review the current literature looking at crosstalk between immune cells, stromal cells, and IECs: how does the immune system potentially alter the ISC niche, and how do IECs influence intestinal immunity? We discuss the latest research using single cell RNA sequencing and intestinal organoid cultures to help answer these questions. A better understanding of this complex crosstalk can help lead to a better understanding of intestinal biology in general, and more efficient therapeutic approaches to treat IBD.

    View details for DOI 10.1002/JLB.3MIR0120-567R

    View details for Web of Science ID 000546468300026

    View details for PubMedID 32057139

  • Mycobacterium avium Subspecies paratuberculosis Infects and Replicates within Human Monocyte-Derived Dendritic Cells. Microorganisms Rees, W. D., Lorenzo-Leal, A. C., Steiner, T. S., Bach, H. 2020; 8 (7)


    Mycobacterium avium subspecies paratuberculosis (MAP), a member of the mycobacteriaceae family, causes Johne's disease in ruminants, which resembles Crohn's disease (CD) in humans. MAP was proposed to be one of the causes of human CD, but the evidence remains elusive. Macrophages were reported to be the only cell where MAP proliferates in ruminants and humans and is likely the major producer of TNFα-associated inflammation. However, whether human dendritic cells (DCs), another major antigen-presenting cell (APC), have the ability to harbor MAP and disseminate infection, remains unknown.Human monocyte-derived dendritic cells (moDCs) were infected with MAP and phagocytosis and intracellular survival were quantified by immunofluorescence (IF) and colony counts, respectively. MoDC cytokine expression was measured via ELISA and their activation state was measured via flow cytometry.We showed that MAP can infect and replicate in human moDCs as means to evade the immune system for successful infection, through inhibition of the phago-lysosome fusion via the secretion of protein tyrosine phosphatase PtpA. This mechanism initially led to a state of tolerance in moDCs and then subsequently caused a pro-inflammatory response as infection persisted, characterized by the upregulation of IL-6 and TNFα, and downregulation of IL-10. Moreover, we showed that moDCs have the ability to phagocytose up to 18% of MAP, when exposed at a multiplicity of infection of 1:1.Infection and subsequent proliferation of MAP within moDCs could provide a unique means for the dissemination of MAP to lymphoid tissue, while altering immune responses to facilitate the persistence of infection of host tissues in CD.

    View details for DOI 10.3390/microorganisms8070994

    View details for PubMedID 32635236

    View details for PubMedCentralID PMC7409171

  • Adaptive immune response to Clostridium difficile infection: A perspective for prevention and therapy EUROPEAN JOURNAL OF IMMUNOLOGY Rees, W. D., Steiner, T. S. 2018; 48 (3): 398-406


    Clostridium difficile infection (CDI) is one of the most important nosocomial illnesses and a major cause of morbidity and mortality. While initial treatment of CDI is usually successful, unprovoked relapses remain an important and frustrating problem. This review examines the literature describing the natural immune response to CDI, and to what extent it can explain the propensity for relapses. In particular, we discuss studies on antibody and, to a lesser extent, B cell and T cell responses in CDI. Despite years of study, there remains incomplete understanding of the natural antibody response to the major pathogenic toxins, TcdA and TcdB, and other bacterial antigens, in CDI. Recent literature suggests that a specific subset of neutralizing antibodies that target the putative carbohydrate-binding domains of TcdB and possibly TcdA have the greatest protective ability. This is further supported by recent successful clinical trials of a humanized monoclonal antibody to the major toxin TcdB. A better understanding of how and why the most protective adaptive immune response develops may lead to improved vaccine and therapeutic targets for recurrent CDI.

    View details for DOI 10.1002/eji.201747295

    View details for Web of Science ID 000427008700002

    View details for PubMedID 29272036

  • Identification of peptide sequences that selectively bind to pentaerythritol trinitrate hemisuccinate-a surrogate of PETN, via phage display technology BIOPOLYMERS Kubas, G., Rees, W., Caguiat, J., Asch, D., Fagan, D., Cortes, P. 2017; 108 (2)


    The present research investigates the identification of amino acid sequences that selectively bind to a pentaerythritol tetranitrate (PETN) explosive surrogate. Through the use of a phage display technique and enzyme-linked immunosorbent assays (ELISA), a peptide library was tested against pentaerythritol trinitrate hemisuccinate (PETNH), a surrogate of PETN, to screen for those with amino acids having affinity toward the explosive. The results suggest that the library contains peptides selective to PETNH. Following three rounds of panning, clones were picked and tested for specificity toward PETNH. ELISA results from these samples show that each phage clone has some level of selectivity for binding to PETNH. The peptides from these clones have been sequenced and shown to contain certain common amino acid segments among them. This work represents a technological platform for identifying amino-acid sequences selective toward any bio-chem analyte of interest.

    View details for DOI 10.1002/bip.22997

    View details for Web of Science ID 000407991800005

    View details for PubMedID 27711976