Albert Einstein Cancer Center

This laboratory recently cloned the transporter that mediates intestinal absorption of folates and established that the molecular basis for the rare genetic disorder, hereditary folate malabsorption, is due to loss-of-function mutations in this gene (Cell 127:917-928, 2006). We named this carrier the Proton-Coupled Folate Transporter (PCFT). Postdoctoral fellows are being recruited to participate in a broad spectrum of studies directed to understanding the structure/function and molecular regulation of this transporter, its role in development and developmental defects, the mechanisms of physiological regulation, and its pharmacological importance in the treatment of cancer with antifolate drugs.

  PCFT is a carrier that functions optimally at low pH; hence, its expression and role in folate absorption that occurs within the acid microclimate of the upper small intestine. This transporter is, however, expressed ubiquitously in many human tissues that are in neutral pH environments. Of special interest is the role PCFT plays in the transport of folates into the central nervous system. This function is based upon the observation that individuals with hereditary folate malabsorption have defects both in intestinal folate absorption and transport of folates into the brain. PCFT is also expressed in most human cancers and may be an important route of delivery of antifolate chemotherapeutics to cancer cells within the acid milieu of solid tumors. An area of particular interest is directed to the novel antifolate - pemetrexed, recently approved for the treatment of several human cancers.This agent, a thymidylate synthase inhibitor, has a very high affinity for PCFT. Studies are exploring the role of PCFT as a determinant of the efficacy of pemetrexed. We recently reviewed the biochemical and molecular pharmacology of this agent (Molecular Cancer Therapeutics  6:404-417, 2007). 

 The range of experimental approaches in the laboratory extend from molecular genetic to biophysical/electrophysiological methodologies. Candidates will be considered with diverse backgrounds, from physiology to molecular biology.   For other publications from this laboratory search Goldman ID on PubMed.