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Research in the Mark Donowitz Lab is primarily focused on the development of drug therapy for diarrheal disorders, intestinal salt absorption and the proteins involved including their regulation, and the use of human enteroids to understand intestinal physiology and pathophysiology. We study two gene families initially recognized by this laboratory: mammalian Na/H exchangers and the subgroup of PDZ domain containing proteins present in the brush border of epithelial cells called NHERF family. A major finding is that NHE3 exists simultaneously in different sized complexes in the brush border, which change separately as part of signal transduction initiated by mimics of the digestive process. Relevance to the human intestine is being pursued using mini-human intestine made from Lgr5+ stems cells made from intestinal biopsies and measuring function via two-photon microscopy.
Recent advances in molecular and cellular biology, the emergence of more sophisticated animal models of human disease and the development of sensitive, high-resolution imaging systems enable the study of pathophysiology noninvasively in unprecedented detail. The overall goal of our work is to develop new techniques and agents to study human disease through imaging. We concentrate on two areas, i.e., cancer and central nervous system processes. Our work extends from basic chemical and radiochemical synthesis to clinical translation.