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Benjamin Feldman, Ph.D.
Investigator
Medical Genetics Branch
Head
Vertebrate Embryology Section
B.A. University of California at Berkeley, 1985
Ph.D. Columbia University, 1995
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Dr. Feldman's laboratory performs basic research in developmental biology, using zebrafish as a model. During early embryonic stages, stem cells undergo coordinated movements and differentiate into distinct tissues, through a process termed gastrulation, forming the basic vertebrate body plan. Elucidating the molecular and cellular changes underlying gastrulation is a central goal of developmental biology that is also relevant to medical research on stem cells, cancer and developmental anomalies. Dr. Feldman's research specifically focuses on the differentiation of the mesoderm and endoderm embryonic lineages, which give rise to the blood, heart, gut and other vital tissues.
A body of research has shown that signaling by the Nodal subclass of TGF-related ligands is necessary and sufficient for establishing much of the mesoderm and endoderm. This includes Dr. Feldman's own previous work characterizing the roles of the zebrafish Nodals - Squint (Sqt) and Cyclops (Cyc) - and the zebrafish Lefty family of Nodal antagonists, in the specification of mesoderm and endoderm and in directing gastrulation movements.
Here at NHGRI, Dr. Feldman's group continues to examine the Nodal signaling pathway, recently discovering environmental factors that affect the phenotypic penetrance of mutations in the sqt gene, and identifying Nodal-independent functions for a transcription factor, FoxH1, that also acts in the Nodal signaling pathway.
To help elucidate the molecular and cellular events underlying gastrulation movements, Dr. Feldman's group is also performing a loss-of-function screen for RhoGEF proteins. RhoGEFs are critical regulators of the RhoGTPase class of cellular proteins, which have key roles in the control of cellular shape and movement. They are using antisense nucleic acid analogues to prevent selected RhoGEF genes from being translated into proteins and are investigating the potential cell movement anomalies that arise, using a novel high throughput time lapse system.
Classical embryological studies have determined when and where mesendoderm cells are specified in a wide range of organisms. But the ability to study these cells in isolation has remained limited. Dr. Feldman has devised a technique called FACS-assisted microdissection of photolabeled cells (FAM-P), which his laboratory has used to isolate zebrafish mesendoderm precursor cells. They are now investigating the behavior of these cells in embryological assays and are also examining the mesendoderm precursor transcriptome. This strategy has identified a set of uncharacterized mesendoderm-specific genes whose functions are currently being investigated by the Feldman laboratory.
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Last Updated: September 5, 2008
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