Studies on infectious diarrhea in cancer patients include descriptive and prospective studies on the risk factors and clinical features of viral (norovirus, rotavirus, adenovirus, cytomegalovirus) and bacterial (Clostridium difficile, diarrheagenic E. coli) associated diarrhea in in the context of microbiome and metagenomic studies in hematopoietic stem cell transplant recipients.
The laboratory studies how variations in host genes that code for known or putative pathogen receptors, mediators of innate immunity, inflammation, cell death, autophagy and antibacterial peptides and lectins are associated with either susceptibility to gastrointestinal infection or disease severity in both immunocompetent and immunocompromised individuals as well as in patients with cancer.
The lab members use human intestinal enteroids (miniguts) obtained from intestinal stem cells present in the crypts of healthy volunteers and patients with malignancies or immunocompromised states, the laboratory studies the molecular basis for infection using different bacterial commensals and diarrheagenic E. coli pathotypes as model organisms. This model allows identifying bacterial virulence factors needed for attachment, colonization and invasion during acute and chronic phases of infection.
Human intestinal enteroids and the communities of enteric organisms they can support will allow the laboratory to study how prebiotics, probiotic organisms and commensals contribute to intestinal epithelium resilience to radiation induced injury, loss of barrier function and colonization by mucosal pathogens during chemotherapy, intestinal graft versus host disease following hematopoietic stem cell transplantation and as drivers for intestinal malignancies.