Mark Joseph Selby, Ph.D.
136 Galewood Circle
San Francisco, CA 94131

(415)753-2295

Professional Experience

From August 1990 to present: Chiron Corporation, Emeryville CA

September 1994-present: Senior Scientist

Currently I supervise two experienced technicians. One has worked at Chiron for 10 years and the other 7 years. We have been involved in multiple projects, ranging from exploring technologies to enhance expression of HCV envelope glycoproteins to developing novel systems for high-level stable expression. We employ technologies that include RT PCR, immunofluroescence, cell fractionation, gradient centrifugations, cell transfections and analyses thereafter in addition to a host of standard molecular biology techniques. We utilize yeast, baculovirus, viral, bacterial and mammalian expression systems to express recombinant proteins for a variety of purposes, including for diagnostics, vaccine production and assay development.

I have interacted with the cellular immunology group to divise reagents and protocols to address issues of antigen presentation in genetic immunization in mice. We have made significant contributions in understanding the generation of immune responses in vivo and dissecting those responses.

I served on an NIH grant review panel as an ad hoc member and I am often solicited by the Veterans Administration to review grant applications as an outside reviewer. I have frequently been solicited to be a speaker to outside groups touring Chiron laboratories. I presented my HCV results at an International Hepatitis meeting in Australia. I have also collaborated with outside investigators that have led to publications.

February 1993 to September1994: Principal Scientist

Working with a single technician, I made contributions to the Hepatitis C project. In addition to characterizing deletion mutants of the HCV envelope proteins and defining at what position secretion was possible, I examined various interactions between the two envelope proteins as well as with a non-structural protein of the virion polyprotein. I presented these results at an International Hepatitis meeting in San Diego.

For less than one year I was associated with the HIV program. Specifically, I supervised another technician and we were able to prepare vectors for stable expression of novel gp120 envelope clones with designated V3 sequences. The cDNA clones were characterized for expression by immunoprecipitation as well as for interaction with soluble CD4.

August 1990-August 1993 Scientist

I constructed full-length cDNAs that encoded the complete HCV polyprotein. Using these clones, my technician and I were able to define the proteins that were cleaved from the polyprotein. We also characterized their subcellular localizations and began to explore the fate of individual proteins encoded by specific expression clones. We relied principally on the Vaccinia virus-based T7 system to achieve high level expression. I also interfaced with the cellular immunology group by suggesting the use of a cationic lipid to deliver proteins into the class I pathway for subsequent presentation to T-cells, leading to a PNAS publication. I served as an ad hoc member of a SBIR grant review panel.

1987-1990 Post-doctoral research in the laboratory of Dr. B. Matija Peterlin, an Investigator in the Howard Hughes Medical Institute at University of California, San Francisco.

In Dr. Peterlin's laboratory I was responsible for investigating the mechanism of Tat transactivation of the HIV-1 LTR. This led to two first-author publications in Genes & Development and in Cell.

1977-1978. Microbiology Assistant.

At Bactomatic, Inc. of Palo Alto, CA. I was responsible for the preparation of industrial samples for analysis in an automated microbial detection system.

Education

- 1980-1987. Ph.D. Microbiology. University of California, San Francisco.
Thesis Advisor: W. J. Rutter, Ph.D.

Thesis topic: Nerve Growth Factor: Gene structure, function and expression.

- 1978-1980. San Francisco State University. Post-graduate studies.

Advisor: J. Stubbs, Ph.D.

Research Topic: Regulation of HMG-CoA reductase in cultured cells.

- 1972-1976. B.A. Bacteriology. University of California, Berkeley.

Publications

  1. Bell, G.I., Selby, M.J., & Rutter, W.J. (1982). The highly polymorphic region near the human insulin gene is composed of simple tandemly repeated sequences. Nature 295, 31-35.
  2. Eberhardt, N.L., Selby, M.J., Cathala, G., Karin, M., Gutierrez-Hartmann, A., Mellon, S.H., Lan, N.C., Gardner, D. & Baxter, J.D. (1982). The growth hormone gene family: Structure, function, expression and regulation. In Gene Regulation, Academic Press, N.Y. pp235-251.
  3. Scott, J., Selby, M.J., Urdea, M., Quiroga, M., Bell, G.I. & Rutter, W.J. (1983). Isolation and nucleotide sequence of a cDNA encoding the precursor of mouse nerve growth factor. Nature 302, 538-540.
  4. Scott,J., Urdea, M., Quiroga, M., Sanchez-Pescador, R., Fong, N., Selby, M.J., Rutter, W.J. & Bell, G.I. (1983). Structure of the mouse submaxillary mRNA encoding epidermal growth factor and seven related proteins. Science 221, 236-240.
  5. Rutter, W.J., Scott, J., Selby, M.J., Crawford, R.J., Shen, L.-P., Hobart, P., Sanchez-Pescador, R. (1983). Structure of precursors derived from the sequences of cloned cDNAs. In Biochemical and Clinical Aspects of neuropeptides (Koch, G. & Richter, D., eds.), Academic Press, N.Y., pp 293-308.
  6. Darling, T.A., Petrides, P.E., Beguin, P., Frey, E., Shooter, E., Selby, M.J. & Rutter, W.J. (1983). The biosynthesis and processing of protein in the mouse 7S nerve growth factor complex. Cold Spring Harbor Symp. Quant. Biol. 48, 427-434.
  7. Selby, M.J., Barta, A., Baxter, J.D., Bell, G.I. & Eberhardt, N.L. (1984). Analysis of a major human chorionic somatomammotropin gene: Evidence for two functional promoter elements. J.Biol.Chem. 259, 13131-13138.
  8. Darby, J.K., Fedir, J., Selby, M.J., Riccardi, V., Ferrell, R., Siao, D., Goslin, K., Rutter, W.J., Shooter, E.M. & Cavalli-Sforza, L.L. (1985). A discordant sibship analyses between B-NGF and neurofibromatosis. Am. J. Hum. Genet. 37, 52-59.
  9. Edwards, R.E., Selby, M.J. & Rutter, W.J. (1986). Differential RNA splicing predicts two distinct NGF precursors. Nature 319, 784-787.
  10. Scott, J., Selby, M.J. & Bell, G.I. (1986). Isolation of cDNAs encoding mouse nerve growth factor and epidermal growth factor. Meth. Enzymol. 147, 194-207.
  11. Selby, M.J., Edwards, R.H., Sharp, F. & Rutter, W.J. (1987). Mouse nerve growth factor gene: Structure and expression. Mol. Cell. Biol. 7, 3057-3064.
  12. Selby, M.J., Edwards, R.H. & Rutter, W.J. (1987). Cobra nerve growth factor: structure and evolutionary comparison. J. Neurosci. Res. 18, 293-298.
  13. Edwards, R.H. Selby, M.J., Garcia, P. & Rutter, W.J. (1988). Processing of the native nerve growth factor precursor to form biologically active nerve growth factor. J. Biol. Chem. 263, 6810-6815.
  14. Edwards, R. H., Selby, M.J., Mobley, W.C., Weinrich, S.L., Hruby, D.E. & Rutter, W.J. (1988). Processing and secretion of nerve growth factor: expression in mammalian cells with a vaccinia virus vector. Mol. Cell. Biol. 8, 2456-2464.
  15. Peterlin, B.M., Calman, A.F., Kao, S-Y., Selby, M.J., Tong-Starksen, S. & Luciw, P.A. (1988). Activation and trans-activation of HIV-1. In The control of Human retrovirus gene expression. (B.R. Franza, Jr., Cullen, B.R. & Wong-Stall, eds.), Cold Spring Harbor Laboratory, pp. 45-58.
  16. Peterlin, B.M., Calman, A.F., Kao, S-Y., Selby, M.J., Tong-Starksen, S. & Luciw, P.A. (1988). Transcriptional regulation of human immunodeficiency virus type I. In Vaccines 88. Cold Springs Harbor Laboratory, pp. 283-290.
  17. Selby, M.J., Edwards, R.E. & Rutter, W.J. (1989). Analysis of a transcription unit. In Nerve Growth Factors. (R.A. Rush, ed.), J. Wiley & Sons LTD, London. pp. 233-254.
  18. Selby, M.J., Bain, E.S., Luciw, P.A. & Peterlin, B.M. (1989). Structure, sequence and position of the stem-loop in tar determine transcriptional elongation by tat through the HIV-1 long terminal repeat. Genes Dev. 3, 547-558.
  19. Selby, M.J. & Peterlin, B.M. (1990). Trans-activation by HIV-1 Tat via a Heterologous RNA Binding Protein. Cell 62, 769-776.
  20. Chin, D.J., Selby, M.J. & Peterlin, B.M. (1991). Human Immunodeficiency Virus Type I Tat Does Not Transactivate Mature trans-Acting Responsive Region RNA Species in the Nucleus or Cytoplasm of Primate Cells. J. Virol. 65, 1758-1764.
  21. Walker C., Selby, M., Erickson A., Cataldo D., Valensi J.P. & Van Nest G. (1992). Cationic lipids direct a viral glycoprotein into the class I major histocompatibility complex antigen-presentation pathway. Proc. NatÕl. Acad. Sci., 89:7915-8.
  22. Yoo, B.J., Spaete, R.R., Geballe, A.P., Selby, M., Houghton, M. & Han, JH. (1992). 5' end-dependent translation initiation of hepatitis C viral RNA and the presence of putative positive and negative translational control elements within the 5' untranslated region. Virology, 191:889-99.
  23. Selby, M.J., Choo, Q.L., Berger, K., Kuo, G., Glazer, E., Eckart, M., Lee, C., Chien, D., Kuo, C & Houghton , M. (1993). Expression, identification and subcellular localization of the proteins encoded by the hepatitis C viral genome. J. Gen. Virol., 74 1103-13.
  24. Ghosh, S., Selby, M.J. & Peterlin, B.M.. (1993). Synergism between Tat and VP16 in Trans-activation of HIV-1 LTR. J. Mol Biol. 234, 610-619.
  25. Eckart, MR., Selby, M., Masiarz, F., Lee, C., Berger, K., Crawford, K., Kuo, C., Kuo, G., Houghton, M. & Choo, Q.-L. (1993). The hepatitis C virus encodes a serine protease involved in processing of the putative nonstructural proteins from the viral polyprotein precursor. Biochem. Biophys. Res. Commun. 192: 399-406.
  26. Ralston, R., Thudium, K., Berger, K., Kuo, C., Gervase, B., Hall, J., Selby, M., Kuo, G., Houghton, M. & Choo, Q.-L. (1993). Characterization of Hepatitis C Virus Envelope Glycoprotein Complexes Expressed by Recombinant Vaccinia Viruses. J. Virol. 67, 6753-6761.
  27. Lo, S.-Y., Selby, M., Tong, M. & Ou, J.-H. (1994). Comparative Studies of the Core Gene Products of Two Different Hepatitis C Virus Isolates: Two Alternative Forms Determined by a Single Amino Acid Substitution. Virology 199, 124-131.
  28. Houghton, M., Selby, M., Weiner, A. & Choo, Q.-L. (1994). Hepatitis C Virus: Structure, Protein Products and Processing of the Polyprotein Precursor. in Curr. Stud. Hematol. Blood Transf. Eds. Liekola, J., Lundsgaard-Hansen, P. Published by S. Karger, Basel. pp 1-11.
  29. Selby, M.J., Glazer, E., Masiarz, F. & Houghton, M. (1994). Complex processing and protein:protein interactions in the E2:NS2 region of HCV. Virol., 204:114-22.
  30. Houghton, M., Selby, M., Weiner, A., & Choo, Q.L. Hepatitis C virus: structure, protein products and processing of the polyprotein precursor. (1994). Current Studies in Hematology and Blood Transfusion, 61:1-11.
  31. Yoo, B.J., Selby, M.J., Choe, J., Suh, B.S., Choi, S.H., Joh, J.S., Nuovo, G.J., Lee, H.S., Houghton, M & Han, J.H. (1995). Transfection of a differentiated human hepatoma cell line (Huh7) with in vitro-transcribed hepatitis C virus (HCV) RNA and establishment of a long-term culture persistently infected with HCV J. Virol., 69:32-8.
  32. Lo, S.Y., Selby, M.J. & Ou, J.H. Interaction between hepatitis C virus core protein and E1 envelope protein. (1996). J. Virol., 70:5177-82.
  33. Doe, B., Selby, M., Barnett, S., Baenziger, J. & Walker C.M. (1996). Induction of cytotoxic T lymphocytes by intramuscular immunization with plasmid DNA is facilitated by bone marrow-derived cells. Proc. NatÕl. Acad. Sci, 93:8578-83.
  34. Pasquinelli, C., Shoenberger, J.M., Chung, J., Chang, K-M, Guidotti, L.G., Selby, M., Berger, K., Lesniewski, R., Houghton, M. & Chisari, F.V. (1997). Hepatology, 25: 719-727.

34. Selby, M.J., Doe, B, & Walker, C.M. Virus-specific CTL activity elicited by co-immunization with HIV-1 genes regulated by the bacteriophage T7 promoter and T7 RNA polymerase protein. (1997). J.Virol.,71: 7827-7831.

Return to top

Return to MCB 115/215 Home Page