Philippe M. Soriano Awarded 2017 Edwin G. Conklin Medal

By Marsha E. Lucas

The 2017 Society for Developmental Biology Edwin G. Conklin Medal was awarded to Philippe M. Soriano of the Icahn School of Medicine at Mount Sinai for his extraordinary and sustained research contributions to the field of developmental biology and mentoring of the next generation of scientists. Soriano’s work characterizing PDGF receptors, Src family kinases, and Eph/ephrin has transformed our understanding of receptor tyrosine kinase signaling mechanisms and how specificity is established during development. Using the mouse as a model, he has uncovered mechanisms involved in developmental processes such as neural crest cell migration and craniofacial development. His loss-of-function c-Src mouse was one of the first targeted mutations in mice.

Throughout his career, Soriano has generated revolutionary tools that continue to advance the mouse development community. He pioneered gene-trapping technology in embryonic stem cells and identified the ubiquitously expressed ROSA26 locus. He went on to generate the R26R Cre recombinase reporter mouse line, one of the most widely used mouse lines in the world.

Born in the United States to French parents, Soriano spent most of his childhood in New York City. Growing up he collected sea shells and wanted to be a marine biologist. In his Conklin Medal lecture, he shared how caring for one of those shells eventually necessitated some medical intervention.

Soriano’s interest in science was piqued as a high school student. He attended a French Lycée where he received a bilingual education and was fortunate to be taught by an “absolutely fantastic [science] teacher.”

“This guy actually turned out to be a postdoc. But, he was trying to make ends meet so he was teaching as well. And he was incredibly enthusiastic,” Soriano said in a July interview. “I remember going when I was like 16 or 17 years old to the Rockefeller Institute . . . to plate out some bacteria . . . and of course everything got contaminated, but it was very exciting.”

His instructor, François Bouvier, a postdoc with Norton Zinder at Rockefeller introduced Soriano and his classmates to various aspects of biology including the lac operon. This was how he became interested in genetics.

After graduating from high school, Soriano left the US to attend college at the University of Paris where he studied biochemistry. Most undergraduates did not do research at that time, but he spent a summer at the Weizmann Institute in Israel working on tRNA processing. Upon his return, he volunteered in Giorgio Bernardi’s lab at the University of Paris where he studied genome organization. In 1975, Soriano received his Maîtrise-ès-Sciences, the equivalent of an undergraduate degree in the US and decided to continue in Bernardi’s lab for graduate school.

"I was fascinated by the papers of Roy Britten and Eric Davidson suggesting that repetitive DNAs might be involved in gene regulation and wanted to work on genome organization.” Soriano compared the properties of mouse and human DNA, analyzing their GC content and heterogeneity. He also compared the distribution of actin genes across both genomes.

Upon completing his second doctorate in 1982, Soriano did a short postdoc at Centre National de la Recherche Scientifique (CNRS) in Paris before joining Rudolf Jaenisch’s lab in 1984 at the Heinrich Pette Institute in Hamburg, Germany and later the Whitehead Institute in Cambridge, Massachusetts.

His projects focused on two major areas. The first was using retroviruses as cell lineage tags.

“What this essentially addressed were questions of founder cells in the early embryo,” Soriano said. “How many cells all together can give rise to the embryo?“

He infected mouse embryos at the 4- to 16-cell stage with a retrovirus that integrated into the genome. The retrovirus could then be used to track descendants of those early cells and determine what they became.

His second focus was on insertional mutagenesis. A germline insertion of a retrovirus into the 5’ end of a gene could cause a null mutation. “Rudolf was the first person to really do this in an efficient way. It was essentially doing knockouts before knockouts were available,” Soriano said. He characterized an embryonic lethal mutation called Mov 34 which turned out to be a proteasome subunit.

When Soriano took his first independent position in 1987 at Baylor College of Medicine in Houston, TX, he began to think about a more efficient mechanism for knocking out genes in mice. His colleague in Jaenisch’s lab, Eric Barklis, found that “classic retroviruses could insert into embryonic carcinoma cells by essentially a splicing mechanism,” Soriano said. This became the basis for his promoter (gene) trap vectors that could both knock out a gene’s function and mark its expression. He placed a promoterless β-galactosidase gene downstream of a strong splice acceptor into a retroviral vector in reverse orientation (ROSA). When this vector inserted into the genome in the right frame and orientation, a mutation was introduced and the gene’s expression pattern revealed.

At this same time, Soriano became interested Src kinases and generated the c-Src kinase null mutant—one of the first targeted knockouts in mice. Soriano’s lab would go on to knockout and characterize five more Src kinase family members revealing the functional redundancy of this gene family.

In 1993, Soriano left Baylor for the Fred Hutchinson Research Center in Seattle, WA. He began to work on growth factor signaling, particularly the PDGF receptor as it was known to interact with Src.

In the late nineties, he returned to a mouse identified in his original gene trap screen—the ubiquitously expressed ROSA 26 mouse. Soriano understood the value of this locus which showed expression throughout development and did not code for an essential gene. He generated the ROSA 26 Cre reporter strain one of the most widely used mouse strains in the field. It allowed scientists to test the expression patterns of their Cre recombinase-expressing strains.

Soriano’s colleagues have expressed their appreciation for his generosity in openly sharing reagents and tools that he has generated over the years. This without a doubt has benefited the larger developmental biology community many times over.
In 2008, Soriano moved his lab to the Icahn School of Medicine at Mount Sinai in New York where he has continued to study the role growth factor and protein tyrosine kinase signaling pathways in development.

Throughout his career, Soriano has mentored dozens of trainees who have gone on to independent research careers in academia and the private sector. “If I take people in the lab, I think that I have a responsibility to them in terms of mentoring,” he said. “I have very high expectations, but at the same time, I’ve learned over the years that every single person is different and that all of my trainees are going to adopt their own style.”
An important aspect of Soriano’s mentoring philosophy is he involves his trainees in the grant writing process—circulating drafts, getting feedback, then revising accordingly. “In a way it becomes a group effort with everybody contributing concepts. At the same time, it also teaches everybody how to write proposals which is very useful,” he said.

Soriano recounted how colleagues reacted to the work of one of his students. “The thesis committee turned to me and said, ‘Phil, you’re not allowed to write your student’s thesis proposal.’ And I said, ‘Well, I didn’t.’ And he said, ‘Well, it reads like one of your grants.’ And I said, ‘I can’t help it if they emulate my style.’”

This is one of the most rewarding parts of his career. “To see my former trainees blossom and grow . . . that is what makes it all worthwhile,” he said.

Soriano acknowledged several people who have been his champions throughout his journey as a scientist. As a teenager, family friend, René Lavigne encouraged him to aim high and have passion for whatever he chose to do in life. Rudolf Jaenisch ingrained in him “the excitement of doing research because he’s still incredibly passionate,” Soriano said. Finally, he is indebted to Marianne Bronner. “Marianne is this extraordinarily positive, enthusiastic person and she taught me to be a better person and about how to mentor others by just bringing out the best in them,” he said.

Receiving the Conklin Medal was overwhelming for Soriano and has been a highlight of his career.

“It was wonderful that it was started off by some of my former trainees. That's incredible. That's an extraordinary recognition,” he said.

It also means a lot because the award is recognition from both his peers and the Society for Developmental Biology. “It's my favorite society because I think that SDB has the same vision of the importance of mentoring as I have,” he said. “I’m really incredibly honored.”

Watch Philippe Soriano's 2017 Edwin G. Conklin Medal Lecture here.