Miguel Reyes-Múgica, MD

My main interests include the study of biological features of a group of disorders knows as "neurocristopathies". In particular, the biology of congenital nevi, and the improvement of diagnostic approaches to the complex neural crest malformation called Hirschsprung disease.

In our laboratory we concentrate in pediatric melanocytic proliferations, in particular Giant Congenital Melanocytic Nevi and a relatively rare associated entity called neurocutaneous melanocytosis (NCM). Patients with this condition are born with large pigmented nevi and later develop meningeal/brain melanocytic proliferations. Little is known about the biology of these lesions and how they compare with other, more conventional melanocytic proliferations, such as malignant melanoma. Our past efforts have centered on studying genes associated with familial melanoma, which apparently are not involved in this condition. Now we are working in collaboration with a number of clinical and surgical researchers, and with the support group Nevus Outreach, Inc., we have established a tissue repository for samples samples derived from patients afflicted with these conditions. In addition, a recent gift from a generous family was received to support our tissue repository, which has now been renamed as "The Gavin Bailey Tissue Repository for Neural Crest Disorders". At the time of this report, we have accumulated samples from approximately 130 patients afflicted with Giant Melanocytic Nevi, including 21 patients with NCM. In collaboration with Dr. Marina Nikiforova, from the Molecular Pathology Laboratory, we have interrogated our samples in regard to their NRAS, BRAF (and other target genes) status. Our results showing BRAF mutations in NCM patients, as well as a particular phenotype associated with BRAF mutations in Giant Nevi, were presented at the joint SPP/PPS meeting in Birmingham, UK, in September 2014, and published in January of 2015. An Editorial comment on these studies appeared in Dermatology Times. This advanced genetic and morphological characterization of NCM lesions, will improve our understanding of their biology, allowing us to discover potential targets for therapy. We have also found that not only mutations, but amplification of mutated NRAS appears to play a significant role in melanomagenesis in the context of NCM. This observation has been accepted for publication in Melanoma Research. We have ongoing collaborations with Ruth Halaban from Yale, and are working with Dr. Harper Price from Phoenix Children's Hospital to accrue more tissues from her patients. Dr. Stewart Cramer, an expert in the field of nevogenesis, and are working with a group of pediatric and adult nevi, establishing comparisons in terms of their immunophenotype and maturation patterns.

An additional field of interest is the pathology of pediatric testicular lesions. We continue working with the groups of Pediatric Endocrinology and Pediatric Urological Surgery in order to analyze patients with Disorders of Sex Development, trying to expand their characterization. This work is also in collaboration with Dr. Katja Gwin, from Southwestern University. In this context, I have recently published 20 out of 25 chapters (peer-reviewed articles) for a supplement dedicated to Pediatric Testicular Pathology, sponsored by the Society for Pediatric Pathology, the bound volume will be published in 2016, but each chapter/article will be finished (as of this writing only 5 remain in review) by the end of 2015.

Lastly, I continue collaborative work with the ELGAN (Extremely Low Gestational Age Neonate) group, and also work on other areas of General Pediatric Pathology, specifically, tumor pathology.