2010 Distinguished Research Career Award
Stephen P. Goff, PhD. Higgins Professor of Biochemistry and Molecular Biophysics and Microbiology, Investigator, Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons
Throughout his distinguished career, Dr. Goff has strategically and cleverly leveraged viruses to decipher how normal cells enable virus replication, yet defend against pathogenic infection, or are co-opted to drive malignant transformation or fatal immunodeficiency
Dr. Goff developed the first methods to deliver recombinant DNA molecules into mammalian cells by employing SV40 virus, and was among the first to prepare molecular clones of retroviruses. He isolated the Abelson murine leukemia virus; identified the v-abl oncogene that is the cause of the viral cancer; and discovered the c-abl proto-oncogene in the normal mouse chromosome. Dr. Goff's work led to realization that ABL is aberrantly expressed in chronic myelogenous leukemia in humans and led to the derivation of the efficacious anticancer drug Gleevec. Dr. Goff defined the functional domains of viral pol gene products, which are separable into the, RNA/DNA polymerase and RNase H domains, and integrase. Dr. Goff identified the integrase function that inserts proviral DNA into the host chromosome, which is the basis for retroviral vector transduction and a major target of successful anti-HIV-1 drugs
Utilizing the power of the yeast two-hybrid system, genetic screens, and somatic cell genetics, Dr. Goff has discovered several host gene products that interact with retroviral protein or RNA and modulate infectivity and escape from host restriction by distinct mechanisms. For example, cyclophilin A, a host prolyl isomerase, binds specifically to HIV-1 Gag, and regulates both infectivity and escape from host restrictions; the novel zinc-finger antiviral protein (ZAP) binds specific sequences in viral RNAs and directs their degradation; TRIM28 mediates primer binding site-targeted silencing of retroviruses that utilize Lys1,2 tRNA in embryonic cells; and eIF3f affects 3' end processing of HIV-1 and can inhibit viral replication. To date sixty predoctoral and postdoctoral scientists under the mentorship of Dr. Goff have contributed to this exceptional research of broad scope and impact.
Dr. Goff received the engraved crystal award sculpture and presented the special lecture "Innate Immunity against Infectious Diseases: New Paradigms from Host Restriction of Retrovirus Replication". Dr. Goff presented a second lecture entitled "RNA Structures Regulating Retrovirus Replication", both in April 2010 at the The Ohio State University.
Dr. Goff's visit was sponsored jointly by the Center for Retrovirus Research and the Dept of Veterinary Biosciences, Dept of Molecular Virology, Immunology and Medical Genetics, and the Comprehensive Cancer Center Viral Oncology Program.
Dr. Stephen Goff (left) receives Career Award crystal from Center for Retrovirus Research Associate Director Dr. Kathleen Boris-Lawrie.
Dr. Goff during his distinguished research seminar presentation to Center for Retrovirus Research and OSU faculty, students, and staff.
Dr. Goff presents a second lecture at the Retrovirus Center weekly Lab Meeting.