Faculty Appointments
Associate Professor of Surgery
Associate Professor of Cell & Developmental BiologyAssociate Professor of Pathology, Microbiology and Immunology
Education
Ph.D., Old Dominion University, Norfolk, VirginiaM.S., Eastern Virginia Medical School, Norfolk, VirginiaB.A., Wake Forest University, Winston-Salem, North Carolina
Research Description
The goal of our research program is to define the microbial- and immune-derived factors that influence human intestinal stem and epithelial cell homeostasis and regeneration following infection and/or damage using complex human organoid co-culture models we have developed. Since 2011, my laboratory has adopted the methods established by Sato and Clevers to indefinitely propagate human intestinal organoids derived from stem cells obtained from healthy donors or patients with GI disorders, including metabolic disease, inflammatory bowel disease, and colorectal cancer. My laboratory has helped establish the methods to grow human organoids as monolayers to better mimic luminal infection (e.g., bacterial, viral, fungal) and pathogenesis. This methodology was essential for my laboratory to establish the methods for co-culturing primary human monocyte derived macrophages and neutrophils with human intestinal organoid monolayers. The results from our studies support the concept that human intestinal organoids functionally recapitulate various aspects of intestinal homeostasis as well as disease pathogenesis. Our studies using human organoids to generate ex vivo human models of diarrheal diseases have been funded by the National Institutes of Health (NIDDK, NIAID, NCATS, NCI), the Department of Defense, and pharma. In addition, my laboratory also contributes to collaborative funded projects such as the NIDDK-funded Intestinal Stem Cell Consortium, a NIAID-funded P01 on mucosal immune responses to enteropathogens, and the NCI-funded P50 SPORE in Gastrointestinal Cancer. My laboratory has successfully trained numerous laboratories (academic, government, and industry) how to establish and study complex human intestinal organoid models.
Research Keywords
Cell Biology; Microbe-Host Interactions; Regenerative Medicine
Publications
Zachos NC, Vaughan H, Sarker R, Est-Witte S, Chakraborty M, Baetz NW, Yu H, Yarov-Yarovoy V, McNamara G, Green JJ, Tse CM, Donowitz M. A Novel Peptide Prevents Enterotoxin- and Inflammation-Induced Intestinal Fluid Secretion by Stimulating Sodium-Hydrogen Exchanger 3 Activity. Gastroenterology [print-electronic]. 2023 Oct; 165(4): 986-998.e11-998.e11. PMID: 37429363, PMCID: PMC11283679, PII: S0016-5085(23)04766-2, DOI: 10.1053/j.gastro.2023.06.028, ISSN: 1528-0012.
Bouffi C, Wikenheiser-Brokamp KA, Chaturvedi P, Sundaram N, Goddard GR, Wunderlich M, Brown NE, Staab JF, Latanich R, Zachos NC, Holloway EM, Mahe MM, Poling HM, Vales S, Fisher GW, Spence JR, Mulloy JC, Zorn AM, Wells JM, Helmrath MA. In vivo development of immune tissue in human intestinal organoids transplanted into humanized mice. Nat Biotechnol [print-electronic]. 2023 Jun; 41(6): 824-31. PMID: 36702898, PMCID: PMC10264243, PII: 10.1038/s41587-022-01558-x, DOI: 10.1038/s41587-022-01558-x, ISSN: 1546-1696.
Maeda K, Zachos NC, Orzalli MH, Schmieder SS, Chang D, Bugda Gwilt K, Doucet M, Baetz NW, Lee S, Crawford SE, Estes MK, Kagan JC, Turner JR, Lencer WI. Depletion of the apical endosome in response to viruses and bacterial toxins provides cell-autonomous host defense at mucosal surfaces. Cell Host Microbe. 2022 Feb 2/9/2022; 30(2): 216-231.e5-231.e5. PMID: 35143768, PMCID: PMC8852832, PII: S1931-3128(21)00582-5, DOI: 10.1016/j.chom.2021.12.011, ISSN: 1934-6069.
Rees WD, Tandun R, Yau E, Zachos NC, Steiner TS. Regenerative Intestinal Stem Cells Induced by Acute and Chronic Injury: The Saving Grace of the Epithelium?. Front Cell Dev Biol. 2020; 8: 583919. PMID: 33282867, PMCID: PMC7688923, DOI: 10.3389/fcell.2020.583919, ISSN: 2296-634X.
Zachos NC, Kovbasnjuk O, Foulke-Abel J, In J, Blutt SE, de Jonge HR, Estes MK, Donowitz M. Human Enteroids/Colonoids and Intestinal Organoids Functionally Recapitulate Normal Intestinal Physiology and Pathophysiology. J Biol Chem [print-electronic]. 2016 Feb 2/19/2016; 291(8): 3759-66. PMID: 26677228, PMCID: PMC4759158, PII: S0021-9258(20)43687-7, DOI: 10.1074/jbc.R114.635995, ISSN: 1083-351X.
Bouffi C, Wikenheiser-Brokamp KA, Chaturvedi P, Sundaram N, Goddard GR, Wunderlich M, Brown NE, Staab JF, Latanich R, Zachos NC, Holloway EM, Mahe MM, Poling HM, Vales S, Fisher GW, Spence JR, Mulloy JC, Zorn AM, Wells JM, Helmrath MA. In vivo development of immune tissue in human intestinal organoids transplanted into humanized mice. Nat Biotechnol [print-electronic]. 2023 Jun; 41(6): 824-31. PMID: 36702898, PMCID: PMC10264243, PII: 10.1038/s41587-022-01558-x, DOI: 10.1038/s41587-022-01558-x, ISSN: 1546-1696.
Maeda K, Zachos NC, Orzalli MH, Schmieder SS, Chang D, Bugda Gwilt K, Doucet M, Baetz NW, Lee S, Crawford SE, Estes MK, Kagan JC, Turner JR, Lencer WI. Depletion of the apical endosome in response to viruses and bacterial toxins provides cell-autonomous host defense at mucosal surfaces. Cell Host Microbe. 2022 Feb 2/9/2022; 30(2): 216-231.e5-231.e5. PMID: 35143768, PMCID: PMC8852832, PII: S1931-3128(21)00582-5, DOI: 10.1016/j.chom.2021.12.011, ISSN: 1934-6069.
Rees WD, Tandun R, Yau E, Zachos NC, Steiner TS. Regenerative Intestinal Stem Cells Induced by Acute and Chronic Injury: The Saving Grace of the Epithelium?. Front Cell Dev Biol. 2020; 8: 583919. PMID: 33282867, PMCID: PMC7688923, DOI: 10.3389/fcell.2020.583919, ISSN: 2296-634X.
Zachos NC, Kovbasnjuk O, Foulke-Abel J, In J, Blutt SE, de Jonge HR, Estes MK, Donowitz M. Human Enteroids/Colonoids and Intestinal Organoids Functionally Recapitulate Normal Intestinal Physiology and Pathophysiology. J Biol Chem [print-electronic]. 2016 Feb 2/19/2016; 291(8): 3759-66. PMID: 26677228, PMCID: PMC4759158, PII: S0021-9258(20)43687-7, DOI: 10.1074/jbc.R114.635995, ISSN: 1083-351X.