I grew up in Fort Lee, New Jersey, close to the George Washington Bridge across from New York City. My dad worked in the city as a manager of a shirt button manufacturing company. My mother and father did not attend college but they both were very supportive and encouraged my interest in science. For Christmas each year, they generously would find a way to purchase the microscope, chemistry set, telescope, erector set, etc. that I requested each year.
My sister, two brothers and I attended Fort Lee public schools. At an early age, I realized that I most enjoyed mathematics and the sciences. After elementary school, I was placed in an honours programme with advanced classes in science and math. In high school, I was selected to attend a summer science curriculum at New York University.
During the late 1960s, the TV series “The Undersea World of Jacques Cousteau” highlighting the adventures of undersea exploration had a big impact on me. I decided to apply to universities with strong oceanography programmes. In 1972, I entered the University of Rhode Island (URI) majoring in biology. After having the opportunity to go out on a research vessel in the Atlantic Ocean, I quickly realized that much of the marine research being done at that time was not as exciting as portrayed in Cousteau’s TV series. I remained a biology major but was not sure what direction to follow for my future. In my junior year, a genetics class and a microbiology lab opened my eyes to the power of genetics and the advantages of simple model organisms like the bacterium E. coli.
The most memorable highlight of this period, however, was meeting my future wife, Michelle, who also was in her junior year at URI, majoring in music and early education. I was in love. We got married three years later after I started graduate school.
I applied to graduate programmes with an emphasis in genetics and microbiology. I accepted the offer from Harvard’s Department of Microbiology and Molecular Genetics. My four years of graduate school were among the most exciting years of my life. It was challenging and I spent long hours in the lab and in the library studying and reading journal articles (a time before the internet and personal computers). I was captivated by the research I was doing and by the exciting discoveries being made in the laboratories of Thomas Silhavy and Jonathan Beckwith where I was working. My PhD thesis focused on the genetics of protein secretion in E. coli.
In 1980, I applied for a postdoctoral position in Randy Schekman’s lab at the University of California, Berkeley. They were characterizing the first secretion defective mutants in yeast. This allowed me to extend my interests to a eukaryotic genetic model, yeast. In 1981, my wife and I moved cross-country and set out on the next stage of our adventure together.
Initially, the projects I worked on in Schekman’s lab did not succeed. However, rather than being discouraged, I doubled my efforts and returned to lessons learned as a graduate student. Within a few weeks, I had succeeded in developing several useful gene fusion approaches in yeast. After about a year in the Schekman lab, I received phone calls asking if I would consider sending in my resume and apply for open faculty positions. Randy encouraged me to apply and a few months later, I was deciding between several job offers. I accepted the offer from the Division of Biology at the California Institute of Technology. This was an ideal environment for me to build a research programme. I shared a floor with two senior faculties, Mel Simon and Jon Abelson. It was a highly collaborative and supportive environment. I quickly had several outstanding graduate students and postdoctoral research fellows working with me.
We devised a gene fusion-based genetic strategy to identify genes in yeast that encode the cellular machinery required to build the vacuole (lysosome). In just a few years, we were able to identify mutations in 33 genes, termed VPS for Vacuolar Protein Sorting. Independently, Tom Stevens’ lab at the University of Oregon also isolated similar yeast mutants. Together, our labs identified more than 40 VPS genes, many more than we had ever expected. Although uncertain where the analysis of these genes would take us, we began the task of determining the biochemical functions for the protein products of the VPS genes. These studies have occupied my lab for almost 40 years and set the stage for our discovery of the highly conserved ESCRT machinery. I am truly indebted to and grateful for the exceptional students and postdocs who have worked with me during these years.
In 1991, I was recruited to the University of California, San Diego School of Medicine by George Palade, the father of modern cell biology. Roger Tsien, a brilliant chemical biologist, had his lab just across the hall from mine. At the time, he was developing the Green Fluorescent Protein, GFP, as a tool for live cell imaging. Roger shared his GFP constructs with my lab and GFP became an indispensable tool in our analysis of the VPS pathway.
In 2007, I moved to Cornell University where I am serving as the Founding Director of the Weill Institute for Cell and Molecular Biology. This has been a great opportunity for me to pay forward some of the knowledge and excitement I have experienced to the next generation of young faculty recruited into the Institute.
My wife and I are delighted to be living in beautiful Ithaca, NY with a wonderful community of colleagues and friends. We have two children who are grown and married now. Our daughter Bryanna is a Pediatric Surgeon in Pittsburgh, PA. Our son Kevin is an Anesthesiologist in Albany, NY. We have two wonderful grandchildren and a third on the way. I am very grateful for my family. They bring so much love and joy into my life.
28 October 2021 Hong Kong
