My parents were not like the stereotypical Asian parents; they never pushed in any one direction, they just wanted me to be happy and successful. I am incredibly grateful for the freedom to choose what I wanted. It was never a question that I would apply to college. Yet, at one point I wanted to be an airline stewardess. I thought it was a very glamorous position. After my first plane ride, however, a bout of air-sickness made me rethink my career goals.
I became involved in the sciences towards the start of my junior year in high school. My best friend’s mother was a secretary for Dr. Frank Ruddle at Yale University and asked for assistance to file away reprints. Being that this was my first paying job, I
worked diligently to get the work done as fast and proficiently as possible. Dr. Ruddle noticed my assiduousness and asked me to remain in his laboratory to gain knowledge of scientific research. I was thrilled; for a junior in high school that was very “cool”. I remained working for Dr. Ruddle part time during the school years and full time during the summers. During that period, somatic cell hybrids were the primary method in
mapping specific genes to chromosomes. I learned basic techniques in gel electrophoresis, sterile tissue culture, the handling of rodents, and the preparation, and staining, of chromosome karyotypes. I worked for Dr. Ruddle for the remainder of my years at high school and college.
Upon my graduation from college with a B.S. in mathematics, I was unsure of my future. I remained in the Ruddle lab for an additional two years. During my time there, I befriended many individuals, many of whom are well known scientists today. The majority of my colleagues suggested that I attain a graduate degree in the field of biological sciences. I ultimately decided to attend Albert Einstein College of Medicine to pursuit a Ph.D. under the guidance of my mentor, Dr. Frank Lilly. Much of the valuable techniques, as well as an acquired intellectual capacity in the field of research from being in the Ruddle lab, facilitated my short but successful graduate studies. While there, my graduate research was focused on the development of spontaneous lymphoma in the progeny of two inbred strains of mice with no known predisposition to lymphoma. We had demonstrated that the onset of spontaneous T-cell lymphoma in the progeny was a result of genetic complementation. I learned mouse genetics from Frank Lilly and, to this day, I remain performing my own animal studies; a practice instilled in me from Frank Lilly.
Subsequent to attaining my Ph.D. in genetics I carried out my postdoctoral training at Columbia University where I began work on cell transformation and DNA tumor virus, SV40, under the guidance of Dr. Robert Pollack. During my second year of postdoctoral training, Dr. Pollack became Dean of Columbia College. He requested that, in his absence, I remain to manage his laboratory. My responsibilities included, but were not limited to, directing the research activities of seven graduate students in his laboratory. I am proud to say that all of them completed their research requirements, attained their Ph.D.s, and obtained excellent postdoctoral positions. Currently, all of them continue to be productive, successful scientists in various academic institutions and pharmaceutical companies.
During my tenure at Columbia University I worked closely with Dr. Pollack. Together we published several papers and secured a number of grant supports. We were also able to recruit three additional graduate students as well as one postdoctoral fellow. After the conclusion of nine years, Dr. Pollack returned to the laboratory and I began my search for a permanent, independent position.
I was recruited as an assistant professor by Dr. Allan Conney, the chairman of the Department of Chemical Biology, School of Pharmacy, Rutgers University. I have been a faculty member at the School since 1992 during which I ascended through the ranks from assistant professor to associate professor and now to full professor.
While at Columbia University, I became interested in the regulation of cell differentiation. Through utilizing molecular cloning techniques and functional assays we identified two small fragments of genomic DNA each with the ability to induce adipocyte differentiation when introduced into a variety of fibroblasts. When I began my position as assistant professor at Rutgers University I took this project with me. I expanded the studies in whole animals by making transgenics with the cloned DNA with the intention to look for the generation of “obese” mice. None of them became fat but one founder showed pigmentation on the ears by 7-8 month of age. The pigmented foci were identified to be melanoma. This finding was very exciting and I switched the focus of my research to melanoma. With the help of investigators from the National Institute of Health (NIH), we identified several BAC clone comprises about 1 megabase surrounding the host/transgene region. We identified and cloned three genes within that region. Using each of the candidate genes as a probe, we showed one of them to be differentially expressed between tumor and normal samples. The gene was metabotropic glutamate receptor 1 (Grm1). In order to distinguish between the causes and consequences of aberrant Grm1 expression in tumor samples, a second transgenic line was made with cDNA of Grm1 under the regulation of a melanocyte-specific promoter, Dct (dopachrome tautomerase). This new transgenic line displayed a melanoma susceptibility phenotype nearly identical to the original one. These results demonstrated ectopic expression of an otherwise normal protein in an anomalous cell type is sufficient to induce tumor development in vivo. We then extended our studies to the human system. We examined human melanoma biopsies and cell lines, and demonstrated ectopic expression of GRM1 in about 40% of these samples, suggesting that GRM1 may play a role in the onset of some human melanomas.
Our aims and goals for the next five years are to concentrate on human melanoma cells. Melanoma can be a very aggressive disease. Oftentimes, melanoma occurs, is treated, and then later resurfaces in a form unresponsive to chemotherapy. In our work, we hope to identify a new way of treating the disease. There are not many rewards or satisfaction in this work, but if we can find a way to better or extend the life of a patient suffering from melanoma – this is something money can not buy. Our proposal will focus, specifically, on experiments that begin to unravel complex networks that result in aberrant expression of genes in human melanoma cells. Specifically, we would like to ascertain if GRM1 expression is required for the maintenance of transformed phenotypes and to test GRM1 for its potential as a therapeutic target in the treatment of melanoma. Ultimately we will be able to begin to examine the mechanisms that bring about the deregulation of GRM1 expression in human melanomas.
My involvement in the pigment cell research field has been intense but brief. If not for the generous encouragement, advice, and valuable tools provided by so many investigators in this field, I feel that my research would not have advanced to where is today. In particular, I am grateful to Drs. Abdel-Malek, Bar-Eli, Bastian, Bennett, Chin, Fisher, Halaban, Hearing, Hendrix, Herlyn, Medrano, Pavan, Pollock, Ronai, and Trent.