Email

sb691007@bcm.edu

Positions

Associate Professor

Virol & Micro: Estes
Baylor College of Medicine
Houston, TX US

Education

Advanced Training from Baylor College Of Medicine

01/1999 - Houston, TX United States

Ph.D. from Baylor College Of Medicine

01/1998 - Houston, TX United States

B.A. from Rice University

01/1993 - Houston, TX United States

Professional Interests

• Cell biology and physiology of the intestine and liver

Professional Statement

The intestinal epithelium has many functions including (1) barrier function which protects against damage induced by radiation, toxins, pathogens, and trauma, (2) facilitating nutrient uptake by being the portal to exchange substances between the lumen and underlying tissues, and (3) producing and/or secreting products that regulate a variety of human physiological processes within the body including immune related functions. Due to the complexity of the intestine, our molecular understanding of many human intestinal functions remains somewhat limited. This is due, in part, to the lack of intestinal culture systems that represent normal, nontransformed human cells and include multiple cell types within the complex intestinal villi. Recently, new technology using human intestinal stem cells (SC) isolated from intestinal biopsies has been developed and now 2D and 3D models of the intestinal epithelium can be established in vitro. Called enteroids, these human “minigut” structures are composed of all five cell types present in the human intestinal epithelium: stem cells, enterocytes, goblet cells, Paneth cells, and enteroendocrine cells. These mini-gut cultures recapitulate many functions of the intestinal epithelium and provide a new, exciting preclinical platform and model to understand mechanisms and pathways that are modulated in the normal, human epithelium. It is the hope that these pathways can be used as targets to improve the overall health of the intestinal tract.

Currently my research projects are focused on using enteroid cultures to understand how stem cells are activated in response to epithelial damage induced by viral infections. Viruses are outstanding models for discovery of fundamental host responses including novel molecular pathways that regulate the intestinal epithelium. Human rotavirus and norovirus infections of the enteroid cultures are being used to identify upstream signals that induce stem cell proliferation to regenerate the viral damaged epithelium and the downstream effects these signals have on epithelial differentiation and function. To complement this work, we are also using a murine model of rotavirus infection to examine the epithelial response to viral infection within the complex intestinal environment. We are also using intestinal enteroid cultures to gain a better understanding of the pathogenesis of human rotavirus infection and to characterize the epithelial immune response that is induced by the infection. Additional work is focusing on the establishment of a human in vitro entero-hepatic co-culture model in which physical coupling and functional crosstalk are features of the multicellular platform. These platforms are being used to investigate both biological pathways as wells as drug-induced responses. Lastly, enteroid cultures are being used to identify functional effects of the microbiome on the intestinal epithelium. Areas such as enhancement of barrier function, proliferation, immune response, and metabolic activity are being investigated.

Websites

Selected Publications

• Saxena, K., Blutt, S.E., Ettayebi, K., Zeng, X., Broughman, J., Crawford, S., Karandikar, U., Sastri, N., Conner, M., Opekun, A., Graham, D., Qureshi, W., Sherman, V., Foulke-Abel, J., In, J., Kovbasnjuk, O., Zachos, N., Donowitz, M., Estes, M. "A New Model to Study Human Rotavirus Infection, Host Restriction and Pathophysiology.." Journal of Virology. 2016;90:43-56. Pubmed PMID: 26446608
• Ettayebi, K., Crawford, S.E., Murakami, K., Broughman, J.R., Karandikar, U., Tenge, V.R., Neill, F.H., Blutt, S.E., Zeng, X.L., Qu, L., Kou, B., Opekun, A.R., Burrin, D., Graham, D.Y., Ramani, S., Atmar, R.L., Estes, M.K. "Replication of human noroviruses in stem cell-derived human enteroids.." Science. 2016;353:1387-1393. Pubmed PMID: 27562956
• Foulke-Abel, J., In J., Kovbasnjuk, O., Zachos, N.C., Ettayebi, K., Blutt, S.E., Hyser, J.M., Zeng, X.L., Crawford, S.E., Broughman, J.R., Estes, M.K., Donowitz, M. "Human Enteroids as an Ex-Vivo Model of Host-Pathogen Interactions in the Gastrointestinal Tract.." Exp Bio Med.. 2014;239(9):1124-1134. Pubmed PMID: 24719375
• Zachos, N.C., Kovbasnjuk, O., Foulke-Abel, J., In, J., Blutt, S.E., de Jonge, H.R., Estes, M.K., Donowitz, M. "Human Enteroids/Colonoids and Intestinal Organoids Functionally Recapitulate Normal Intestinal Physiology and Pathophysiology.." J Biol Chem.. 2016;291:3759-3766. Pubmed PMID: 26677228