Posts classified under: Secondary Faculty

Research Interests

Mark Donowitz, M.D., has had a distinguished career of scientific discovery, mentorship of young researchers and advocacy for the gastroenterology specialty. Dr. Donowitz is LeBoff Professor of Medicine and Professor of Physiology, Director of the Hopkins Center for Epithelial Disorders at The Johns Hopkins University School of Medicine, and is Founding Director of the NIH/NIDDK Hopkins Conte Digestive Diseases Center for Basic and Translational Research. He was President of the American Gastroenterological Association 2006-2007. He also served as President of the Gastroenterology-Research Group. He has received the Distinguished Achievement Award and as well as the Davenport Memorial Prize from the American Physiology Society, and the Distinguished Achievement in Basic Science Award from the American Gastroenterological Association, and is a Fellow of the American Association for the Advancement of Science. His scientific focus has been to understand regulation of intestinal Na absorption in normal digestive physiology and abnormalities that contribute to diarrheal diseases. His group was the first to recognize the mammalian Na/H exchanger gene family, to clone the epithelial isoforms, and to trace the evolutionary development of the gene family. He has examined structure/function aspects of the exchangers and identified the large, multiprotein complexes in which the epithelial NHEs function. In addition, his group identified a gene family of PDZ containing brush border proteins called the NHERF family which are scaffolding proteins which interact with NHE3 and are involved in forming the multiprotein complexes, are critical for its regulation, and take part in its association with the cytoskeleton. He has pioneered use of human mini-intestines made from normal human subjects to advance understanding of human digestive physiology and pathophysiology especially related to host-pathogen interactions.

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Research Interests

Dr. Dawson’s laboratory is actively engaged in discovering and defining cell signaling pathways that lead to either neuronal survival or neuronal death. The lab has named a new cell death process Parthanatos. In the brain, Parthanatos is important in ischemic and excitotoxic injury and in models of Parkinson’s disease. The cell death mechanism involves nuclear activation of poly(ADP-ribose) polymerase and mitochondrial release of apoptosis inducing factor in the integration of the death signal; current research aims to further understand how this pathway works. She has characterized neuronal injury and survival pathways in cell, fly and mouse models of Parkinson’s disease and stroke. She is focused on several monogenic forms of Parkinson’s disease including parkin and LRRK2, as well as the new sporadic model of Parkinson’s disease using pre-formed fibrils of alpha synulcein in order to begin to define the biochemical signaling important to Parkinson’s disease. Yeast, cellular, fly and mouse models along with human neuronal cultures and human postmortem tissue explore survival and disease signaling events relevant to Parkinson’s disease. . In addition to cell death, the team also strives to understand how cells survive by characterizing survival genes and proteins involved in preconditioning. The Dawson laboratory employs advanced technologies in high throughput screening, next generation sequencing including RNA Seq and ChIP Seq, ribosomal foot printing, and high throughput proteomic analysis coupled with advanced computational biology to investigate signaling networks important in stroke, Parkinson’s disease and other neurodegenerative disorders. The overarching goal of the research is to understand death and survival signaling in order to identify new targets for therapeutic development.

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My focus is in developing gene or pharmacologic therapies for genetic diseases in which mutations lead to chronic diseases.  I devote significant effort to developing treatment strategies for cystic fibrosis (CF), a lethal autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.  I study treatment options for other ABC transporters, similar to CFTR, such as ABCA4, which causes, Stargardt macular degeneration which leads to macular destruction in children. I am actively involved in developing strategies for reducing cyst formation in Autosomal Dominant Polycystic Kidney disease , the most common dominant genetic disorder in humans.