YOUNG INVESTIGATOR AWARD

The Young Investigator Award was established by Council to recognize a body of work
which has contributed significantly to the diagnosis and understanding of human disease.
This Award is restricted to USCAP members who are under the age of 45.




Dr. Mark Rubin is a recognized leader in the field of prostate pathology and cancer biomarker development. He has focused on novel methods for translating basic science observations into tests which may potentially be clinically applicable in the area of prostate disease. This work done in collaboration with investigators in the United States and Europe is helping us to better distinguish lethal from indolent prostate cancer.

Dr. Rubin, a native New Yorker, graduated Phi Beta Kappa from the University of Wisconsin-Madison majoring in French Studies. He lived for two years in Rennes, France studying at the Univeristé de Haute-Bretagne before beginning medical school at Mount Sinai in New York. After graduating from medical school in 1988, Dr. Rubin completed a general surgical internship at Mount Sinai Hospital. He spent two years in Germany at the Berlin Heart Transplant Center developing an animal model to study rejection in combined heart-lung transplants. It was during this research hiatus from clinical medicine that Dr. Rubin became interested in pathology after a chance encounter with Harold Stein, the well-known hematopathologist. Dr. Rubin retuned to the United States in 1992 and started anatomic pathology residency at Georgetown Medical Center. Interactions with Drs. Jeffery Cossman and Norio Azumi introduced him to the burgeoning field of translational research. As an anatomic pathology fellow at Johns Hopkins, he first recognized the significance of closely coordinating research efforts between basic science, pathology, and a well-defined clinical cohort.

As an Assistant Professor in Pathology at the College of Physicians and Surgeons of Columbia University, Dr. Rubin began pursuing his goal of developing a translational research program in prostate pathology working closely with pathologists, urologists and basic researchers. Initial work focused on evaluating prostate cancer for loss of heterozygosity at 10q23, and PTEN mutations using laser capture microdissection. Dr. Rubin was involved in the early evaluation of a blood-based enhanced RT-PCR method for detecting circulating PSA-producing cells. In 1998, Dr. Rubin was recruited to join the Department of Pathology, Urology and University of Michigan Prostate Cancer Specialized Program of Research Excellence (SPORE) as their urologic/prostate pathologist and director of the prostate tissue core. With enthusiasm he expanded the rapid autopsy program at Ann Arbor, which allowed for the rapid harvesting of tumor samples shortly after death due to hormone refractory metastatic prostate cancer, and which provided valuable tissue samples to help begin the important task of distinguishing latent from lethal prostate cancer.

Dr. Rubin worked with untiring enthusiasm and additionally developed a tissue microarray core in order to begin the process of evaluating multiple biomarkers (in combination) in a large number of clinical samples without comprising this finite resource. As part of a National Cancer Institute funded project, Dr. Rubin worked closely with renowned genitourinary pathologists to create the necessary informatics tools to deal with clinical, pathology, and image data associated with the tissue microarray studies. Dr. Rubin is co-inventor of an Internet-based tool (TMA Profiler http://rubinlab.tch.harvard.edu) to evaluate and store tissue microarray data for biomarker development.

The development of the tissue-based infrastructure was critical in translating observations from cDNA expression array analysis of samples from metastatic and clinically localized prostate cancer. In collaboration with Arul M. Chinnaiyan at Ann Arbor, their group was among the first to report on their observations using this novel high-throughput technology. Work published in Nature (two papers in 2001 and 2003 an unusual achievement for a practicing anatomic pathologist!) identified novel prostate cancer biomarkers including hepsin, pim-1 kinase, MTA1and EZH2. Hepsin has been identified as being consistently over expressed in prostate cancer and is currently being evaluated as a molecular beacon for prostate cancer imaging. Dr. Rubin's group was one of the first groups to characterize the novel prostate cancer biomarker, alpha-methlyacyl-CoA racemase (AMACR). They were the first to describe its expression in multiple tumor types besides prostate cancer and current work is evaluating the immune response to AMACR with the goal of developing a serum test for prostate and colon cancer.

Since 2002, Dr. Rubin has been the Chief of the Urologic Pathology Service at the Brigham and Women's Hospital in Boston and Associate Professor of Pathology at the Harvard Medical School. He has established Dana Farber/Harvard Cancer CenterTissue Microarray Core facility, which serves the Harvard community. He currently works on both the Dana Farber Harvard and University of Michigan Prostate SPOREs. Dr. Rubin serves as the study pathologist for the Physicians' Health Study Prostate Program in collaboration with the Harvard School of Public Health. Dr. Rubin continues to expand clinical cohorts in order to validate biomarkers to the point of clinical use. Dr. Rubin is currently conducting large collaborative projects with the University Hospital of Ulm in Germany, Örebro University in Sweden, and the CHU Mondor in Creteil, France.

Dr. Rubin is funded by the NIH and DOD and serves in a leadership position at the national level, working as an external advisor to the National Cancer Institute in areas of biomarker development. Dr. Rubin was a member of the prostate cancer working group for the 2003 WHO Blue Book. He is also on the Steering Committee of the Medical Treatment of Prostate Symptoms (MTOPS) Biomarker Development Consortium to develop biomarkers for benign prostatic hyperplasia. He has given numerous invited lectures and most recently spoke at the American Association for Cancer Research on the effects of finasteride (Proscar) on prostate cancer in the first Public Forum on this topic.

Dr. Rubin is actively involved in training urologic pathology and post-doctoral fellows in the area of translational research. In the past 5 years, his fellows have presented over 50 abstracts at the annual USCAP meetings. In 2002, his trainees were the recipients of both the Stowell-Orbison and ADASP Autopsy Awards for work done on an autopsy series of men with metastatic prostate cancer. Dr. Rubin himself has played an active role at the USCAP. He served as an abstract reviewer for the past 4 years, gave a Long Course talk on the Molecular Genetics of Human prostate cancer (2003) and is on the 2004 Faculty for the Molecular Pathology Course. The impact of his valuable contributions in anatomic pathology was recognized when he was honored with the 2003 Arthur Purdy Stout Society Prize for recognition of significant career achievements in Surgical Pathology.

In summary, Dr. Rubin has contributed a substantial and important body of work which, most notably, has significantly impacted our understanding (and ability to predict) the biology of prostate cancer. This work is already having direct implications for the clinical care of patients with this disease. Dr. Rubin epitomizes what is best in academic surgical pathology in this new era of translational research and his work truly embodies what this term conveys taking basic scientific discoveries from the lab and using them to enhance patient care. His work is a credit to our Academy.