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Nadeem Moghal

Assistant Professor of Oncological Sciences

B.S. McGill University

Ph.D. Harvard University

Research

References

nadeem.moghal@hci.utah.edu

Nadeem Moghal's Lab Page

Research

My lab studies the mechanisms by which cell fate is determined, and how these mechanisms are deregulated in cancer.  We use forward genetic approaches in the nematode C. elegans to study the gene networks that control vulval epithelial progenitor cell fate.  As a more clinically relevant model, we also study stem/progenitor cells from the upper airways of human lungs.  One intense area of study is how epidermal growth factor receptor (EGFR) signaling is regulated in these cell types, and how this signaling pathway controls the fate of these progenitor cells.  EGFR signaling is widely-used in development, and when excessive, contributes to a wide-range of human cancers.

C. elegans vulval development: C. elegans is a 1 mm soil nematode that exists as males and self-fertilizing hermaphrodites.  It is easily manipulated with genetic and molecular tools, and a laser microbeam can be used to ablate individual cells.  C. elegans has one EGFR-like gene, which regulates vulval development in hermaphrodites.  We study the mechanisms that precisely ensure that only a restricted number of vulval progenitor cells adopt vulval fates.  Excessive EGFR signaling causes extra cells to adopt a vulval fate (Multivulva phenotype), and too little signaling prevents the required number of cells from adopting a vulval fate (Vulvaless phenotype).  Since the total number of cells contributing to vulval tissue can be counted, we can precisely quantify any deviations from normal EGFR signaling.  Using unbiased forward genetic approaches, we have uncovered a number of novel regulatory mechanisms.  These include auto-inhibition in key EGFR signaling molecules, as well as regulation through heterologous plasma membrane, cytoplasmic, and nuclear molecules.  In addition, we have uncovered a novel regulatory pathway involving excitation of neighboring muscle and neuronal cell populations.  Current work involves studying these regulatory mechanisms through genetic and biochemical methods.

Human tracheal/bronchial epithelial cell differentiation and lung cancer:  Lung cancer is the leading cause of cancer-related deaths worldwide, and is one of the human cancers most often linked to excessive EGFR pathway activity.  In fact, EGFR inhibitors are currently being used to treat lung cancer patients.  Some of the predominant forms of lung cancer are thought to arise through transformation of unidentified cell populations in the tracheal/bronchial tubes.  We have recently established conditions to grow and differentiate primary cultures of human tracheal/bronchial epithelial cells in vitro.  We are currently using these cells to molecularly characterize specific stem/progenitor cell populations, to elucidate the signals that normally regulate their proliferation and differentiation, and to determine how EGFR and other signaling abnormalities contribute to lung cancer.

References