Robert H. Costa: 1957-2006
Authors: Pradip Raychaudhuri, Lester F. Lau, Dennis Grayson, Jack Kaplan
Journal: Hepatology (2006)

Robert Henry Costa, Ph.D., an authority on liver biology and cancer, died peacefully on September 1, 2006, at his home in Oak Park, IL. Rob (his nickname) 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 (HSV), 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, that 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. The Darnell lab at that time 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. Lai and 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 the HNF3 and FoxA groups of factors, some of which were later shown to also be 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 get out of the comfort zone and apply completely new 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 forkhead 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 old 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 Proc Natl Acad Sci U S A (Wang X, Kiyokawa H, Dennewitz MB, Costa RH. 2002;9:16881-16886) and the article was featured in ASBMB Today (February 2003 issue, pp. 16-17). His lab 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 lab demonstrated 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 levels of FoxM1b. His lab also discovered that FoxM1b is a target of the tumor suppressor ARF. This work was published in Genes Dev (Kalinichenko VV, Major ML, Wang X, Petrovic V, Kuechle J, Yoder HM, et al. 2004;18:830-850). 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 gene expression and cell proliferation. He organized several prestigious national conferences on liver gene expression and development, and chaired scientific sessions in major international conferences in the United States and Europe. He served on the editorial boards of several important journals, including Hepatology, which he held in high regard and considered the best journal in liver research. In the past 5 years alone, he published 10 papers in this journal. A respected innovator and beloved colleague, Rob trained numerous graduate students and postdocs, and helped mentor many junior faculty members. In February of 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 sorely. Dr. Costa was a valuable contributor, reviewer, and member of the Editorial Board. His presence will be sorely missed. Robert H. Costa Pradip Raychaudhuri*, Lester F. Lau*, Dennis Grayson*, Jack Kaplan*, * Department of Biochemistry and Molecular Genetics University of Illinois at Chicago Chicago, IL.