Conversations with Lipid Leaders: Dr. Julie Saba

Tell us a little bit about yourself (current role, background, family, etc.)

I’m a Professor of Pediatrics in the division of pediatric hematology/oncology at UCSF where I direct a lab that has been conducting basic and translational biomedical research in the area of sphingolipid metabolism and signaling since the mid-1990’s. I grew up in Rockville, Maryland, went to school in Baltimore, Maryland and completed my medical training and PhD in Durham, North Carolina but have now lived in Oakland, California for the past 25 years. I have two younger brothers who, along with my mother, still live in the Washington, D.C., area which I visit quite often. I have a son who is a public interest attorney living in Brooklyn and a beloved cat named Mouse whom I rescued from the pound during the pandemic.

What do you consider the greatest breakthrough in lipid research in recent years?

I’m not sure I can pinpoint any one breakthrough as a singular achievement that stands out above all others. Let me share some perspective. When I began working in lipid research in the early 1990’s, it was both technically challenging (as convenient lipid delivery systems had not yet been developed), and academically challenging (as most reviewers of our papers thought of lipids as detergents and lipid-mediated biology as artifacts). The gradual recognition of lipids as active participants in cell biology, and contributors to human health and the pathomechanism of disease (other than cardiovascular sludging) has been the most remarkable (albeit painfully slow) breakthrough I have witnessed. I remember hearing a talk around 2000 by Randy Schekman in which he shared his fantastic accomplishments elucidating the protein sorting mechanisms underlying vesicular trafficking. At the end, I asked him, “But what about the lipids, Randy? They are present in all the vesicles. Surely, they must also play a role.” He looked at me like I was from Mars and said nothing. I believe he had already realized the relevance of the lipids at the time but was not ready to talk about his findings publicly yet! He published his first sphingolipid paper about a year later.

Did you always envision yourself becoming a scientist? If not, what did you want to be when you grew up? Who influenced you to become a scientist?

That’s a long story. My father was a physician scientist, and I had spent time in his lab during the summers in high school to help develop skills he thought might be useful to me. His lab was located in a concrete government building that had no windows and was built during the cold war and designed to withstand a direct nuclear hit. Needless to say, it was quite oppressive to a teenage girl who wanted nothing more than to spend my summer days on the beach. At that point, I was nearly certain I did NOT want to become a scientist. I was intending to be a poet and started down that path. However, I guess it’s difficult swimming against the current of one’s own genetics, and eventually fate took me in the direction I must have been destined for. I went to medical school, fell in love with pediatrics and eventually with pediatric oncology, although I still had no desire to conduct lab-based research. It was not until some of the children I cared for succumbed to their leukemia that I was inspired to dedicate my life to research. Witnessing the failure of the medical community to save these children was heartbreaking. It was then that I finally understood that research held the potential to transport us to a day in the future when each child with cancer could be treated in a personalized manner with a medical regimen specifically designed to circumvent the genetic defects present in that child’s cancer cells.

Are you still able to have close interactions with your patients?

I have not directly cared for pediatric patients in decades, due to the disconnect between my research and the oncology clinic. However, our work is now moving toward clinical application in a very exciting but unexpected way. In 2017, we were involved in the discovery of sphingosine phosphate lyase insufficiency syndrome (SPLIS), a rare inborn error of sphingolipid metabolism caused by mutations in SGPL1, the human homolog of a gene I first identified in budding yeast at the outset of my scientific career. It’s exciting and personally meaningful to be developing therapeutics for children affected by this devastating condition. Using telemedicine, I have been interacting with SPLIS patients and their physicians worldwide over the past two years, and it has been extremely gratifying to help in the care and support of these children. I am now in the planning stages of establishing a clinic in which my team and I may conduct natural history studies and clinical trials in SPLIS.

What made you want to focus your attention on sphingosine-1-phosphate and S1P Lyase?

I was searching for novel pathways involved in cancer. Sphingolipid metabolites were intriguing to me, as they seemed to influence cell growth, migration, differentiation and death. The genes that regulate their interconversion could potentially regulate cell fate and thus seemed apt candidates to function as oncogenes and antioncogenes. However, at the time I began my graduate studies and fellowship, none of the genes in the pathway had been identified — except for one subunit of serine palmitoyltransferase the first enzyme in the sphingolipid biosynthetic pathway. That gene (LCB1) had been identified using a yeast genetic approach, and I decided to use a similar approach, but focusing on the other end of the pathway, the sphingolipid degradative pathway. I did not intentionally focus on S1P or the lyase, but I was able to create a screen that killed wild type yeast cells using D-erythro-sphingosine, whereas L-erythro-sphingosine had no effect. The stereospecificity of the lethality indicated a receptor or enzyme was the target, and so the screen seemed biologically important—leading me to clone DPL1, the first S1P lyase gene, and the rest is history.

What are your hobbies? What do you like to do outside of the lab?

I have a small farm in Bennett Valley (wine country) where I spend time on the weekends (mostly pulling weeds!). I also enjoy hiking, gardening, caring for animals, working for social justice, traveling, reading and spending time with friends.

Do you have a favorite Avanti product or class of products? Or perhaps one that you’ve found most useful in your research?

We perform sphingolipidomics using tandem mass spectrometry regularly, and thus we rely heavily on the commercial standards that Avanti provides for establishing extraction efficiency, performing mass analysis and establishing standard curves. Thank you, Avanti!!!