Sphingosine-1-phosphate: From insipid lipid to a key regulator

Abstract

It is a great honor to be asked to write a "Reflections" article by one of the true icons of biochemistry, Herb Tabor. I felt humbled, especially since it follows many written by biochemists I admire and whose contributions have shaped major advances in biochemistry and molecular biology in the last century. Here I present my personal reflections on my adventure with the bioactive sphingolipid metabolite sphingosine-1-phosphate intertwined with those of my family life as a wife, mother, and grandmother. These reflections brought back many memories of events in my early career that played significant roles in determining the path I have taken for more than 40 years and that brought much fun and satisfaction into my life. It has been an exciting journey so far, with many surprises along the way, that still continues.

Keywords: S1PR; sphingolipid; sphingolipid metabolites; sphingosine 1-phosphate (S1P); sphingosine kinase (SphK).

Figure 1.

A, Professor Meir Wilchek and me working on my first paper. B, my children Shlomit and Michael when we arrived in a new country and I started as a postdoc at NIH in Bethesda.

Figure 2.

Finding gold in a dirt (shmutz) pile. A and B, identification of the first schmutz S1P, produced by phosphorylation of sphingosine as a novel lipid involved in cellular proliferation. Taken from Ref. . This research was originally published in the Journal of Cell Biology. Zhang, H., Desai, N. N., Olivera, A., Seki, T., Brooker, G., and Spiegel, S. Sphingosine-1-phosphate, a novel lipid, involved in cellular proliferation. J. Cell Biol. 1991; 114:155–167. © Rockefeller University Press. C, 600,000-fold purification of SphK1 and isolation of a 49-kDa SphK1 polypeptide.

Figure 3.

Professor Sen-itiroh Hakomori and me at a meeting.

Figure 4.

Walter Shaw, President of Avanti Polar Lipids, presenting the ASBMB Avanti Award in Lipids to Sarah Spiegel in New Orleans in April 2009. Dr. Al Merrill (right), session chair, nominated Sarah Spiegel for the award.

Figure 5.

Photos of attendees at the Gordon Research Conferences on Glycolipid and Sphingolipid Biology (Ventura, CA) in 1998 (top) and in 2014 (bottom).

Figure 6.

S1P: The blind men and the elephant. Reproduced from (83) with permission from Elsevier.

Figure 7.

Virginia's Outstanding Scientist of 2008 ceremony in the Science Museum (Richmond, VA). A, VCU leadership (from left to right): Dr. Jerome Strauss, Dean of the School of Medicine; Dr. Sheldon Retchin, VP for Health Sciences; Dr. Sarah Spiegel; Dr. Frank Macrina, VP for Research and Innovation; Dr. Gordon Ginder, Director of the Massey Cancer Center. B, Dr. Spiegel and the Governor of Virginia, Tim Kaine. C, my family (from left to right): Dr. Shlomit Spiegel Mittler, Dr. Sarah Spiegel, Dr. Sheldon Milstien, Ben Milstien, Sarah Milstien Kennard, Annika Milstien, Fred Kennard, Dr. Michael Spiegel, Liraz Arazi, Oren Arazi, Shula Arazi, Yossi Arazi.

Figure 8.

Our research group at VCU in 2008. Shown (from left to right) are Dr. Dai Shida, Dr. Nitai Hait, Poulami Mitra, Dr. Carol Oskeritzian, Dr. Sheldon Milstien, Dr. Sarah Spiegel, Graham Strub, Megan Price, Dr. Sergio Alvarez, Steve Paugh, Dr. Sandrine Lepine, Dr. Michael Maceyka, Dr. Kazuaki Takabe, and Dr. Dmitri Kapitonov.