Martin Martin, MD

Professor, Department of Pediatrics, David Geffen School of Medicine at UCLA

Dr. Martín’s research interest is in the Pediatric diarrheal disorders. A large proportion of children have a generalized malabsorptive form that has not been characterized clinically, and their molecular basis has yet to be fully elucidated. Dr. Martín recently identified the clinical phenotype and molecular basis of a novel human disorder of intestinal failure characterized by severe congenital generalized malabsorptive diarrhea, and a paucity of enteroendocrine cells. He identified two homozygous mutations in a basic-helix-loop-helix (bHLH) transcriptionalfactor, NEUROGENIN-3 (NGN3) which directs enteroendocrine cell fate determination in early gut progenitor cells along the proximo-distal axis of the intestine. These mutations alter highly conserved amino acid residues that attenuate NGN3’s ability to bind and activate its down-stream targets. They named this disorder Enteric Anendocrinosis, and its description is particularly significant because it highlights for the first time the essential role of enteroendocrine cells in the absorption of simple nutrients. Dr. Martín hypothesizes that this disorder could provide the molecular and cellular framework to classify other poorly understood forms of congenital and transient forms of diarrhea. Indeed, his group has uncovered a series of related, but distinct congenital diarrheal disorders that result in malabsorption. They have also found that a depletion of enteroendocrine cells accounts for the diarrhea seen in several other more common non-congenital forms of diarrhea. Dr. Martín has shown that enteroendocrine cell development and function are an essential component of the process of nutrient assimilation, and that impairment in these processes results in various forms of congenital and acquired diarrheal disorders. Dr. Martín’s group is working with embryonic and somatic stem cells to develop intestinal mucosa to better understand diarrheal and several other disorders. They are also very active in the area of total genome (exome) sequencing to identify other novel inherited disorders of the gastrointestinal tract.