My research interests center on understanding how the formation of complex structures is instructed. Elucidating the regulatory network controlling morphogenesis is relevant both for an understanding of human genetic diseases and congenital malformations, and for ultimately exploiting potential regenerative capacity in adults. My graduate training in human viral gene regulation (University of Chicago) spurred my interest in the molecular biology of transcriptional regulation, an essential component in orchestrating development. As an MD-PhD (Univ. of Chicago and Johns Hopkins Univ. School of Medicine), I became interested in embryonic development as a basis for understanding the developmental mechanisms governing normal human physiology and disease, and I began studying early vertebrate axis formation and limb development during my residency training in Anatomic Pathology at the NCI. My clinical training complements my basic research program and gives me a broad perspective of its potential relevance for understanding the basis of and treatment of human disease, and I also serve as an attending anatomic pathologist for the Laboratory of Pathology at the NIH Clinical Center.
My current research uses limb development as a model for learning how signaling networks orchestrate the formation of a complex 3-dimensional structure, using combined genetic, genomic, and biochemical approaches to study transcription factors and signaling cascades that regulate the formation and pattern of digits and unravel the regulatory hierarchy between early patterning and late digit morphogenesis. A major focus of the lab has been the role of Sonic Hedgehog and its signaling targets, particularly the Gli3 Hedgehog-effector and 5’HoxD homeobox gene targets that interact to regulate the late morphologic realization of early patterning cues.
