Robert H. Costa: In Memoriam (1957-2006)

Abstract

Robert Henry (Rob) Costa, an authority on liver biology and cancer, died on September 1, 2006 at his home in Oak Park, IL. Rob was born in Galesburg, IL and grew up in Bethesda, MD. He attended the University of California at Irvine, where he received his doctorate in Molecular Virology in 1985 under the guidance of Dr. Edward K. Wagner. Rob characterized several genes encoded by the type I herpes simplex virus at a time when many techniques of molecular biology were still in their infancy. Rob was instrumental in identifying the viral transcripts, including the late genes, which are important in the viral life cycle.In 1985, Rob joined the laboratory of Dr. James E. Darnell, Jr. at the Rockefeller University for postdoctoral training. At that time, the Darnell laboratory was testing the hypothesis that tissue-enriched transcription factors were responsible for tissue-specific gene expression and tissue development. Rob, along with two other colleagues, Drs. Eseng Lai and Dennis R. Grayson, characterized the promoter region of the mouse prealbumin gene, which is mainly expressed in the liver. More importantly, Rob and colleagues discovered and characterized several liver-enriched transcription factors, including HNF3s or FoxAs, some of which were later shown to be also critical for mammalian development. These studies provided insights into mechanisms for liver-specific gene expression and laid the foundation of our current understanding of liver development.Rob joined the Northwestern University Medical School as an Assistant Professor in 1988. In 1989, he moved to the University of Illinois at Chicago where he rose to the rank of professor of biochemistry and molecular genetics. Throughout his career, Rob believed in digging deep for new information with cutting edge technologies. He was an imaginative thinker and was passionate about the process of discovery. He would leave the comfort zone and apply novel approaches much more easily than many of us. He was always generous with his time, reagents, and thoughtful advice. He exuded energy and enthusiasm, making his presence felt in a very positive way.Rob directed a vigorous research program. His laboratory identified a number of the fork-head family of genes that play key roles in liver-specific gene expression. Among his many contributions is the discovery of FoxM1b, a critical gene that is essential for liver development and liver cell proliferation. He showed that increasing the expression of FoxM1b in liver cells of aged mice make them behave as though they were cells in young mice, thereby restoring the proliferation potential of juveniles in aged animals. This work was published in the Proceedings of the National Academy of Science in 2002 and featured in ASBMB Today in the February, 2003 issue. His laboratory showed that FoxM1b plays a crucial role in mammalian cell division by stimulating expression of genes necessary for cell cycle progression. Several genes that regulate G2-M progression are critically dependent on FoxM1b, and cells lacking FoxM1b fail to enter M phase.More recently, Rob's laboratory showed that expression of FoxM1b is essential for the development of liver cancer. Conditional deletion of FoxM1b in the liver rendered mice refractory to hepatocellular carcinoma (HCC) development following treatment with DEN/Phenobarbital, which causes HCC in littermates expressing normal level of FoxM1b. His laboratory also discovered that FoxM1b is a target of the tumor suppressor ARF. This work was published in Genes & Development in 2004. Based on these studies, he pioneered a new approach to treat liver cancer by using small molecules derived from ARF to disrupt the function of FoxM1b. This new approach is currently under development.Widely regarded as a star in the liver field, Rob was a leading authority in the molecular analysis of liver biology and cell proliferation. He organized several prestigious national conferences on liver gene expression and development and chaired scientific sessions at major international conferences in the United States and Europe. He served as an editorial board member and peer reviewer for several prestigious journals, including Hepatology, The Journal Biological Chemistry and several of the AACR journals. In addition, Rob sat on numerous review panels for the NIH.A respected innovator and beloved colleague, Rob trained numerous graduate students and postdocs and helped mentor many junior faculty members. In February, 2006, he was diagnosed with stage IV pancreatic cancer with liver and bone metastases. Rob battled his illness heroically with uncommon courage, grace, and fortitude. He never gave up hope or his sense of humor, and he continued to work assiduously while undergoing chemotherapy. His wife Jane and son Sam, the anchors of his life, made it possible for him to stay optimistic. His death at the height of his career is a tragic loss to science and the scientific community. In him, we will remember an outstanding scientist, a loyal friend, an exemplary mentor, and a fine human being. We will miss him greatly.