Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine

 (photo)

Henry V. Huang

Associate Professor
Phone: (314)-362-2755
FAX: (314)-362-7325
email: huang@wustl.edu

8230 McDonnell Pediatric Research Building
Box 8230 Department of Molecular Microbiology
Washington University School of Medicine
660 South Euclid Avenue
St. Louis, MO 63110-1093.

Research Interests | CV | Publications | Technology for licensing

Research Interests

We study the molecular biology of Sindbis virus, to understand the mechanism of RNA synthesis using RNA templates. We have identified the cis-acting sequences for viral replication and transcription, and we are using an in-vivo library selection method to identify the sequence requirements of the cis-acting sequences. We are also working on identifying the viral proteins that recognize the cis-acting sequences. Our current focus is to characterize in detail how the viral promoter is recognized, by viral and host transcription factors, during initiation of mRNA synthesis.

Our understanding of the molecular biology of Sindbis virus has led to two types of practical applications. First, it has suggested a novel and general approach for designing antiviral drugs, targeting highly conserved elements of the viral genome, including the viral recognition of the cis-acting sequences for initiation of replication and transcription,. It promises to provide broad-spectrum antiviral drugs that are effective against the virus and having minimal impact on host processes, and with very low probabilities of drug-resistance. We are using Sindbis virus as a model system to test this novel approach.

Second, we have developed a series of RNA virus gene expression vectors, derived from Sindbis virus, that give rapid and efficient expression of foreign genes in a wide range of host cells. The Sindbis virus vectors are being used by many research groups to express specific RNAs and proteins in cultured cells and in animals. In our laboratory, we will be using them to express and characterize human developmental gene regulators that are up-regulated during the monocytic differentiation of a human promyelocytic leukemia cell line.

Keywords: Molecular biology and evolution of RNA viruses, RNA virus gene expression vectors. Antiviral drug design.

CV

Present position
1992 - Associate Professor
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri

Education
1972 A.B. Biology, Occidental College, Los Angeles, California
1977 Ph.D. Biochemistry, California Institute of Technology, Pasadena, California. Thesis advisor: Dr. William J. Dreyer.

Professional Experience and Appointments
1982-1992 Assistant Professor
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri
1981-1982 Senior Research Fellow
Division of Biology, California Institute of Technology, with Dr. Leroy Hood
1982Invited Instructor
faculty course on techniques in molecular biology, California State University, Northridge, California.
1980-1981 Senior Research Fellow in Biology and Biomedical Engineering
Divisions of Biology, and Engineering and Applied Science, California Institute of Technology, with Drs. Leroy Hood and Derek Fender
1979-1980 Research Fellow in Biology and Biomedical Engineering
Divisions of Biology, and Engineering and Applied Science, California Institute of Technology, with Drs. Leroy Hood and Derek Fender
1979-1980 Part time Instructor
Division of Biology, California Institute of Technology
1977-1979 American Cancer Society Postdoctoral Fellow
Division of Biology, California Institute of Technology, with Dr. Leroy Hood
1971-1972 Member of BUGSYS design team for computer analysis of video images
Jet Propulsion Laboratory, California Institute of Technology

Honors
1970 Seltzer Award, Occidental College
1970-1972 College Scholar, Occidental College
1972 A.B. Summa Cum Laude, Occidental College
1972 Alpha Mu Gamma, National Honorary Language Fraternity
1972 Phi Beta Kappa
1972 Association for the Advancement of Biomedical Education Award
1972-1977 Danforth Fellow
1976-1977 McCallum Fellowship, California Institute of Technology
1977-1979 American Cancer Society Postdoctoral Fellow
1995-1999 Member, NIH Virology Study Section

International Committees
1997-present International Committee on Taxonomy of Viruses. Togaviridae Study Group

Editorial Responsibilities
1982-Ad Hoc Reviewer: Journal of Virology, Proceedings of the National Academy of Science, USA, Virus Research, Nucleic Acids Research

Professional Society Membership
American Association for the Advancement of Science
American Society for Microbiology
American Society for Virology
Genetics Society of America
Sigma Xi

University Appointments and Committees

Thesis committees 1982-present
Patricia Ahrweiler
Mari Aker*
J.D. Alvarez
Sean Amberg
Marion E. Andrew
Charles F. Austerberry
Frederick G. Barr
Jenny M. Buzan
Alejandro Carillo
David Davido
Anthony M. Dean
Karen W. Dodson
Stacy Finkbeiner
Wadiha Freije
Danny Garza
Brian Greuel
Brooke Harmon		 Jennifer Hertz*
Jeffrey Hiken*
William C. Hollifield*
Roberta Hopmann
Kathryn Kellerman
Mark LaStarza
Julie Lemm
Robin Levis*
Guangpu Li
Randall Little
Thomas M. J. Niederman
Hal Padgett
Elizabeth Paine
J Christian Perez
Michael Reagan
Regina Rowe
Scott R. Schaecher		 Michael V. Seiden
Ping Shen*
Lisa Strelow
David Sweetser
Lai-Wa Tam
Ivan Tarle
Judy A. C. Thomas
Mohammed Tondravi
Manuel Tsiang
Tony Weisstein
Duan-Zhi Wen
Kathleen Weston
Matthew Wielgosz*
Mollie Winfield
Ruth W. Yokoyama
* Thesis advisor of these students

Other committees
1983-5 Member, Nucleic Acids Preliminary Examination Committee
1986 Chair, Nucleic Acids Preliminary Examination Committee
1985-86, 88 Member, Developmental Biology Preliminary Examination Committee
1987 Chair, Developmental Biology Preliminary Examination Committee
1988 Member, Genetics Preliminary Examination Committees
1991 Chair, Virology Preliminary Examination Committee
1983 Member, Cell and Molecular Biology Programs Admissions Committee
1984-87 Secretary, Cell and Molecular Biology Programs Admissions Committee
1988 Secretary, Cell, Immunology and Molecular Biology Programs Admissions Committee
1988-1992 Member, Medical Scientist Training Program Committee
1991 Medical Scientist Training Program Director Search Committee
1990-present Supervisor, Departmental computing services
1986-1988 Member, Steering Committee of the Molecular Biology: Genetics and Biochemistry Program
1988-1991 Co-coordinator, Molecular Biology: Genetics and Biochemistry Program
1991-1992 Coordinator, Molecular Microbiology & Microbial Pathogenesis Program
1991-1992 Member, Governing Committee of the Programs in Cell and Molecular Biology
1990-1991 Senior Advisory Committee
1991 Co-chairman, Cell Molecular Biology Merger Committee
1992 Member, Programs and Student Affairs Committee
1992-1994 Member, Minority subcommittee, Committee on Admissions, School of Medicine
1992-1996 Member, Recruitment Committee of the Division of Biology and Biomedical Sciences
1997 Information Services Committee, of the Medical School Process Improvement Program
1996-2000 Member, Committee on Admissions, School of Medicine
2001-2005 Member, Institutional Biological and Chemical Safety Committee
2005-present Co-chair, Institutional Biological and Chemical Safety Committee

Teaching
1983 Microbiology: Molecular Biology of Prokaryotes
1983, 1984 Foundations in Immunology
1983, 1984 Topics in Immunology
1983, 1986 Regulatory Phenomena in Cell and Molecular Biology
1984 Selected Topics in Developmental Biology: Mechanisms of DNA Recombination and Rearrangement
1987 Advanced Genetics
1989 Practical Applications of Viruses
1990-91 Microbiology
1994 Molecular Virology
1995 Ethics and Research Science
1995-1998Co-coursemaster, Molecular Virology
1997-present Molecular Microbiology and Pathogenesis
1999-2004Coursemaster, Molecular Virology
1999-2001 Microbes and Pathogenesis
2000-2001 Discussion group leader, Nucleic acids and Protein Synthesis
2004 Co-coursemaster, Special Topics in Microbial Pathogenesis
2002-present Co-coursemaster, Microbes and Pathogenesis

Participation on Training Grants
1984-present Cell and Molecular Biology Training Grant
1984-present Program Physician-Scientist Award
1984-present Infectious Disease Training Grant

Peer Review Panels
1982-present Ad hoc and special reviewer / site visit panels, for NIADDK, NIAID, NSF.
1995-1999 Member, Virology study section, NIH.

Community Service
1989-1997 Judge, Monsanto-St. Louis Post Dispatch Science Fair, Honors Division.
1994-2000 Technology Committee, Forsyth School
1995-2003 Board of Trustees, Forsyth School

Publications

  1. Huang, H.V., R.S. Molday and W.J. Dreyer (1973). Isoelectric focusing of rod outer segment membrane proteins. FEBS Letters 37: 285-289.
  2. Lim, R.W., R.S. Molday, H.V. Huang and S.-P.S. Yen (1975). Application of latex microspheres in the isolation of plasma membranes. Affinity density perturbation of erythrocyte membranes. Biochim. Biophys. Acta 394: 377-387.
  3. Hood, L., H.V. Huang and W.J. Dreyer (1977). The Area Code Hypothesis: The immune system provides clues to understanding the genetic and molecular basis of cell recognition during development. J. Supramolec. Struct. 7: 531-559.
  4. Huang, H.V. and W.J. Dreyer (1978). Bursectomy in ovo blocks the generation of immunoglobulin diversity. J. Immunol. 121: 1738-1747.
  5. Hood, J.M., H.V. Huang and L. Hood (1980). A computer simulation of evolutionary forces controlling the size of a multigene family. J. Mol. Evol. 15: 181-197.
  6. Early, P., H. Huang, M. Davis, K. Calame and L. Hood (1980). An immunoglobulin heavy chain variable region gene is generated from three segments of DNA: VH, D and JH. Cell 19: 981-992.
  7. Huang, H.V., S.T. Crews and L. Hood (1981). The arrangement, rearrangement and diversification of antibody genes. In Frontiers in Immunogenetics, W. Hildemann and J. Frelinger (eds), Elsevier-North Holland, New York. pp63-74.
  8. Huang, H.V., S.T. Crews and L. Hood (1981). Diversification of antibody genes through DNA rearrangement. Adv Exp Med Biol 137:475-488.
  9. Crews, S.T., J. Griffin, H. Huang, K. Calame and L. Hood (1981). A single VH gene segment encodes target="ref" the immune response to phosphocholine: Somatic mutation is correlated with the class of the antibody. Cell 25: 59-66.
  10. Huang, H.V., S.T. Crews and L. Hood (1981). An immunoglobulin VH pseudogene. J. Appl. Molec. Genet. 1: 93-101.
  11. Hood, L., M. Davis, P. Early, K. Calame, S. Kim, S. Crews and H. Huang (1981). Two types of DNA rearrangements in immunoglobulin genes. Cold Spring Harbor Symp. Quant. Biol. 45: 887-898.
  12. Hood, L. J. Griffin, S. Crews, H. Huang, M. Kronenberg and S. Kim (1981). Antibody and MHC genes. In Immunoglobulin Idiotypes and their Expression. C. Janeway, E. Sercarz, H. Wigzell and C. Fred Fox (eds), Academic Press, New York. ICN-UCLA Symp. Molec. Cell. Biol. 20: 805-824.
  13. Huang, H.V. and L. Hood (1982). The expression of antibody genes. In Comparative Research on Leukemia and Related Diseases. D.S. Yohn and J.R. Blakeslee (eds), Elsevier-North Holland, New York. pp 169-172.
  14. Hunkapiller, T., H. Huang, L. Hood and J. Campbell (1982). The impact of modern genetics on evolutionary theory. In Perspectives on Evolution. R. Milkman (ed), Sinauer Assoc., Sunderland, Mass. pp 164-189.
  15. Hood, L., J. Griffin, S. Crews, H. Huang, K. Kronenberg and S. Kim (1982). Antibody and MHC genes. Oncodev Biol. Med. 4: 61-79.
  16. Huang, H.V., M. Bond, M. Hunkapiller and L. Hood (1983). Efficient cleavage of proteins at tryptophanyl residues using DMSO-HCl and CNBr. Meth. Enzymol. 91: 318-324.
  17. Huang, H.V. and L. Hood (1983). The ontogenetic and evolutionary origin of V gene formation. Stadler Genetics Symp. Proc. 14: 59-68.
  18. Huang, H.V. and L. Hood (1983). Origins of antibody diversity. In Recombinant DNA and Medical Genetics. L. Porter (ed). Academic Press, New York. Birth Defects Symp. 13: 97-104.
  19. Levis, R., B.G. Weiss, M. Tsiang, H. Huang and S. Schlesinger (1986). Deletion mapping of Sindbis virus DI RNAs derived from cDNAs defines the sequences essential for replication and packaging. Cell 44: 137-145.
  20. Shen, P. and H.V. Huang (1986). Homologous recombination in Escherichia coli: Dependence on substrate length and homology. Genetics 112: 441-457.
  21. Lutz, C.T., T.L. Bartholow, N.S. Greenspan, R.J. Fulton, W.J. Monafo, R.M. Perlmutter, H.V. Huang and J.M. Davie (1987). Molecular dissection of the murine antibody response to streptococcal group A carbohydrate. J. Exp. Med. 165: 531-545.
  22. Schlesinger, S., R. Levis, B.G. Weiss, M. Tsiang and H. Huang (1987). Replication and packaging sequences in defective interfering RNAs of Sindbis virus. In Positive Strand RNA Viruses, M. Brinton and R. Rueckert (eds). Alan R. Liss, New York. pp 241-250.
  23. Siu, G., E. A. Springer, H. V. Huang, L. E. Hood and S. T. Crews (1987). Structure of the T15 VH gene subfamily: Identification of immunoglobulin gene promotor homologies. J. Immunol. 138: 4466-4471.
  24. Lutz, C.T., W.C. Hollifield, B. Seed, J.M. Davie and H.V. Huang (1987). Syrinx2A: An improved lambda phage vector designed for screening DNA libraries by recombination in vivo. Proc. Natl. Acad. Sci. USA 84: 4379-4383.
  25. Levis, R., S. Schlesinger and H.V. Huang (1987). Engineered defective interfering RNAs of Sindbis virus express bacterial chloramphenicol acetyltransferase in avian cells. Proc. Natl. Acad. Sci. USA 84: 4811-4815.
  26. Rice, C.M., R. Levis, J.H. Strauss and H.V. Huang (1987). Production of infectious RNA transcripts from Sindbis virus cDNA clones: Mapping of lethal mutations, rescue of a temperature-sensitive marker, and in vitro mutagenesis to generate defined mutants. J. Virol. 61:3809-3819.
  27. Hollifield, W.C., E.N. Kaplan and H.V. Huang (1987). Efficient RecABC-dependent, homologous recombination between lambda and plasmids requires a phage ninR region gene. Molec. Gen. Genet.210:248-255.
  28. Nag, D. K., H. V. Huang and D. E. Berg (1988). Bidirectional chain terminating DNA sequencing strategy using transposon Tn5-seq as a source of mobile primer sites. Gene 64:135-145.
  29. Polo, J. M., N. L. Davis, C. M. Rice, H. V. Huang and R. E. Johnston. (1988) Molecular analysis of Sindbis virus pathogenesis in neonatal mice using virus recombinants constructed in vitro. J. Virol. 62:2124-2133.
  30. Huang, H.V., P. Little and B. Seed (1988). Improved suppressor tRNA cloning vectors and plasmid-phage recombination. Biotechnology 10:269-83
  31. Schlesinger, S., C. Xiong, R. Levis, C. M. Rice and H. V. Huang. (1988) Development of Sindbis virus and defective interfering RNAs as expression vectors. In Viral Vectors, Y. Gluzman and S. H. Hughes (eds). Cold Spring Harbor Banbury Conference Report. Cold Spring Harbor Laboratory, New York. pp 167-171.
  32. Xiong, C., R. Levis, P. Shen, S. Schlesinger, C. M. Rice and H. V. Huang. (1989) Sindbis virus: an efficient, broad host range vector for gene expression in animal cells. Science 243:1188-1191.
  33. Phadnis, S., H. V. Huang and D. E. Berg. (1989) Tn5supF, a 264 bp transposon derived from Tn5 for insertion mutagenesis and sequencing DNAs cloned in phage lambda. Proc. Natl. Acad. Sci. USA 86:5908-5912.
  34. Shen, P. and H.V. Huang. (1989) Effect of base pair mismatches on recombination via the RecBCD pathway. Molec. Gen. Genet. 218:358-360.
  35. Mi, S., Durbin, R., Huang, H. V., Rice, C. M., and Stollar, V. (1989). Association of the Sindbis virus RNA methyltransferase activity with the nonstructural protein nsP1. Virology. 170:385-391.
  36. Grakoui, A., R. Levis, R. Raju, H. V. Huang and C. M. Rice. (1989) A cis-acting mutation in the Sindbis virus junction region affecting subgenomic RNA synthesis. J. Virol. 63:5216-5227.
  37. Huang, H. V., C. M. Rice, C. Xiong and S. Schlesinger. (1989) RNA Viruses as Gene Expression Vectors. Virus Genes 3: 85-91.
  38. Grakoui, A., R. Levis, R. Raju, S. Schlesinger, H. V. Huang and C. M. Rice. (1990) Cis-acting sequence responsible for Sindbis virus subgenomic RNA synthesis. in New Aspects of Positive-Strand RNA Viruses, M. A. Brinton & F. X. Heinz (ed). American Society of Microbiology, Washington D.C. pp108-115.
  39. Levis, R., S. Schlesinger and H. V. Huang. (1990) The promoter for Sindbis virus RNA-dependent subgenomic mRNA transcription. J. Virol. 64:1726-1733.
  40. Raju, R. and H. V. Huang. (1991) Analysis of Sindbis virus promoter recognition in vivo using novel vectors with two subgenomic mRNA promoters. J. Virol. 65:2501-2510.
  41. Hertz, J. and H. V. Huang. (1992) Utilization of heterologous alphavirus junction sequences as promoters by Sindbis virus. J. Virol. 66: 857-864.
  42. Piper, R.C., C. Tai, C.S. Hahn, C.M. Rice, H. Huang and D.E. James (1992) The efficient intracellular sequestration of the insulin-regulatable glucose transporter (GLUT-4) is conferred by the NH2 terminus. J. Cell Biol. 117:729-743.
  43. Krishnan, B. R., D. Kersulyte, I. Brikun, H. V. Huang, C. M. Berg, and D. E. Berg (1993) Transposon- and PCR-based sequencing of DNAs cloned in lambda phage. Meth. Enzymol.218:258-279.
  44. Hertz, J. and H. V. Huang. (1995) Evolution of the Sindbis virus subgenomic mRNA promoter in cultured cells. J. Virol.69: 7768-7774. (PDF)
  45. Hertz, J. and H. V. Huang. (1995) Host-dependent evolution of the Sindbis virus promoter for subgenomic mRNA synthesis. J. Virol.69:7775-7781. (PDF)
  46. Aker, M. and H. V. Huang. (1996). Extreme heterogeneity of centromeric minor satellite repeats in inbred strains of mice. Mammalian Genome 7:62-64 (PDF)
  47. Frolov, I., T. A. Hoffman, B. M. Prágai, S. A. Dryga, H. V. Huang, S. Schlesinger, C. M. Rice. (1996) Alphavirus-based expression vectors: Strategies and applications. Proc. Natl. Acad. Sci. USA 93:11371-11377. (PDF)
  48. Huang, H. V. (1996) Sindbis virus vectors for expression in animal cells. Curr. Opin. Biotechnol. 7:531-535.
  49. Huang, H. V. (1997) Evolution of the alphavirus promoter and the cis-acting sequences of RNA viruses. in Factors in the Emergence of Arbovirus Diseases, J.-F. Saluzzo and B. Dodet (eds). Elsevier Press, Paris. pp 65-79.
  50. Wielgosz, M., and H. V. Huang. (1997) A novel viral RNA species in Sindbis virus-infected cells. J. Virol. 71:9108-9117. (PDF)
  51. Mouslim C., Hilbert F, Huang H, Groisman EA. (2002) Conflicting needs for a Salmonella hypervirulence gene in host and non-host environments. Mol Micro 45:1019-1027.
  52. Hunag H. V. and S. Schlesinger (2003). Virus-based vectors for gene expression in mammalian cells: Sindbis virus. in Gene Transfer and Expression in Mammalian Cells, S. C. Makrides (ed). Elsevier Press, Amsterdam. pp189-205.
  53. Zwir I, D. Shin, A. Kato, K. Nishino, T. Latifi, F. Solomon, J. M. Hare, H. Huang, E. A. Groisman (2005) Dissecting the PhoP regulatory network of Escherichia coli and Salmonella enterica. Proc. Natl. Acad. Sci. USA 102(8):2862-2867.
  54. Zwir, I., H. Huang, E. A. Groisman (2005) Analysis of differentially-regulated genes within a regulatory network by GPS genome navigation. Bioinformatics 21:4073-4083.
  55. Shin, D., E.-J. Lee, H. Huang, E. A. Groisman (2006) A positive feedback loop promotes transcription surge that jump-starts Salmonella virulence circuit. Science, in press.

Technology for Licensing

Patents
"Automated method for quantitative analysis of biological fluids". US patent 4,327,073.
"Sindbis virus vectors". US patent 5,091,309.
"DNA transposon Tn5seq1". US patent 5,137,829.
"Method of DNA sequencing using DNA transposon Tn5seqL". US patents 5,212,080, 5,869,296.
"Infectious Sindbis virus vectors". US patent 5,217,879.

Sindbis virus gene expression vectors
These are infectious RNA virus vectors with excellent levels of gene expression in a variety of vertebrate and invertebrate cells.
They can be used as expression vectors, vaccine reagents, for non-integrating genetic immunization, etc..

Department of Molecular Microbiology, Box 8230
Washington University School of Medicine
St. Louis, MO 63110-1093 USA
Tel 314-362-2755
FAX 314-362-7325