Yoke Peng Loh, Ph.D.
Section on Cellular Neurobiology
Neurosecretory Protein Biosynthesis, Trafficking and Function in Neurological Diseases and Cancer
We study the cell biology of endocrine and neuroendocrine cells. Our focus is three-fold: (i) investigate the mechanisms of biosynthesis and intracellular trafficking of peptide hormones and neuropeptides and their processing enzymes; (ii) uncover mechanisms involved in the regulation of dense-core secretory granule biogenesis, transport, and exocytosis; and (iii) determine the neurophysiological and pathological roles of the prohormone-processing enzyme carboxypeptidase E (CPE). Our work has led to the discovery of novel molecular mechanisms of protein trafficking to the regulated secretory pathway and identified players and mechanisms that control secretory granule biogenesis and transport in endocrine and neuroendocrine cells as well as uncovered new non-enzymatic roles of carboxypeptidase E and its isoforms in neuroprotection, stem cell differentiation and cancer. Using cell lines, primary cell cultures, and mouse models, such studies have provided a better understanding of diseases related to defects in hormone and neuropeptide targeting, neurodegeneration, depression , memory, learning, diabetes, obesity, and metastatic disease.
Dr. Y. Peng Loh is the head of the Section on Cellular Neurobiology, Division on Molecular and Cellular Biology, NICHD. She and her group study the cell biology of endocrine and neuroendocrine cells, focusing on the mechanisms of biosynthesis and intracellular trafficking of peptide hormones and neuropeptides and their processing enzymes, the regulation of dense-core secretory granule biogenesis, and physiological roles of the prohormone processing enzyme carboxypeptidase E (CPE) and its isoforms, and peptides derived from the neuroendocrine protein, chromogranin A. Her studies have elucidated molecular mechanisms governing protein trafficking to the regulated secretory pathway and identified players and mechanisms that control secretory granule biogenesis and transport in endocrine and neuroendocrine cells and neurons. Recently, she and her team discovered novel neurotrophic roles of CPE in neuroprotection an stem cell differentiation. Her research has also provided a better understanding of diseases such as diabetes, obesity, depression and neurodegeneration. Her group has also cloned a splice variant of CPE encoding a 40kD N-terminal truncated isoform (CPE-deltaN) that is highly expressed in different types of metastatic tumor cells and is an inducer of tumor growth and metastasis. Clinical studies so far have shown that CPE-∆N is a promising, powerful biomarker for predicting future metastasis, and a potential therapeutic target for different malignant cancers. Dr. Loh received her B.Sc. (Hons.) in Biochemistry from University College Dublin, Ireland, and her Ph.D. in Molecular Biology from the University of Pennsylvania. She did her postdoctoral work with Dr. Harold Gainer at NIH and at the Max Planck Institute in Germany. During her career at NIH, Dr. Loh has received numerous honors and awards including the Public Health Superior Service Award, the NIH Director’s Award, the NIH Director’s Award for Mentoring, the FASEB Award for Excellence in Science, and the Women in Endocrinology Mentor Award. She is a member of the Endocrine Society, Society for Neuroscience, and has served on editorial boards. She has authored more than 200 scientific articles published in journals such as Cell, Nature Medicine, Journal of Clinical Investigations, JAMA, and Neuron, the Proceedings of the National Academy of Science, as well as published numerous review articles.
Cheng Y, Rodriguiz RM, Murthy SR, Senatorov V, Thouennon E, Cawley NX, Aryal DK, Ahn S, Lecka-Czernik B, Wetsel WC, Loh YP. Neurotrophic factor-α1 prevents stress-induced depression through enhancement of neurogenesis and is activated by rosiglitazone. Mol Psychiatry. 2015;20(6):744-54.
Cheng Y, Cawley NX, Loh YP. Carboxypeptidase E/NFα1: a new neurotrophic factor against oxidative stress-induced apoptotic cell death mediated by ERK and PI3-K/AKT pathways. PLoS One. 2013;8(8):e71578.
Xiao L, Yang X, Sharma VK, Loh YP. Cloning, gene regulation, and neuronal proliferation functions of novel N-terminal-truncated carboxypeptidase E/neurotrophic factor-αl variants in embryonic mouse brain. FASEB J. 2019;33(1):808-820.
Cheng Y, Cawley NX, Yanik T, Murthy SR, Liu C, Kasikci F, Abebe D, Loh YP. A human carboxypeptidase E/NF-α1 gene mutation in an Alzheimer's disease patient leads to dementia and depression in mice. Transl Psychiatry. 2016;6(12):e973.
Selvaraj P, Xiao L, Lee C, Murthy SR, Cawley NX, Lane M, Merchenthaler I, Ahn S, Loh YP. Neurotrophic Factor-α1: A Key Wnt-β-Catenin Dependent Anti-Proliferation Factor and ERK-Sox9 Activated Inducer of Embryonic Neural Stem Cell Differentiation to Astrocytes in Neurodevelopment. Stem Cells. 2017;35(3):557-571.
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This page was last updated on October 31st, 2019