Biomedical Research Education & Training
Faculty Member

Mitchell, William M., M.D., Ph.D.
Professor of Pathology, Microbiology and Immunology

Lab Url: N/A

Phone Number: 615-322-3238

Email Address: bill.mitchell@vanderbilt.edu

Mitchell, William's picture
Academic history
B.A., Vanderbilt
Ph.D., Johns Hopkins
M.D., Vanderbilt

Office Address   Mailing Address

U-3302 MCN 2561


Research Specialty
Pathogenesis of intracellular microbes (Chlamydia / HIV / SARS-CoV structure-function drug and vaccine design / genetic vaccines) and weapons of bioterroism.

Research Description
The emphasis of research in this laboratory is on intracellular pathogens involved in human disease. Our current focus is on the pathogenesis of two microorganisms: 1) Chlamydia pneumoniae is a recently recognized member of the genus Chlamydia. This obligate intracellular bacterium has been recently linked to a variety of human idopathic inflammatory diseases, 2) Human immunodeficiency virus (HIV) is the etiological agent of the Acquired Immunodeficiency Syndrome (AIDS),3) SARS-CoV which is the etiological agent of the newly emerged disease, Severe Acute Respiratory Syndrome (SARS), and 4) Anthrax and mechanisms of biodefense.

C. pneumoniae is an obligate intracellular pathogen which lacks a mechanism for generating energy and relies on the host cell mitochondria as an energy source. We have developed improved methods for detection (culture, immunoassay, and PCR) of this microbe in human tissue and blood. The organism is difficult to eradicate since elements of the immune system (IFN) and/or antibiotics induce the acquisition of a stringent response in which the organism stops replication and enters an anaerobic phase which we refer to as a cryptic or latent phase. Reactivation of the cryptic phase yields a resumption of replication. We are pursuing an efficacious genetic vaccine using various surface proteins as antigenic targets. Currently we are evaluating a genetic vaccine in which the MOMP gene has been altered for improved expression in transfected eukaryotic tissues in vivo.

Our studies on HIV are currently focused on two targets. The first is the design and synthesis of HIV integrase by the combination of molecular modeling and peptoid synthesis of modeled putative inhibitors. The second is the elimination by site-directed mutagenesis of a region in the HIV envelope which is responsible for antibody-dependent enhancement of infection (ADE). We are evaluating the immune response in model systems to a genetic vaccine expressing ADE defective gp160 or gp120/gp41 of the HIV envelope. .

Publications
Beck, J, Urnovitz, HB, Saresella, M, Caputo, D, Clerici, M, Mitchell, WM, Sch??tz, E. Serum DNA Motifs Predict Disease and Clinical Status in Multiple Sclerosis. J Mol Diagn, 2010

Tang, YW, Sriram, S, Li, H, Yao, SY, Meng, S, Mitchell, WM, Stratton, CW. Qualitative and quantitative detection of Chlamydophila pneumoniae DNA in cerebrospinal fluid from multiple sclerosis patients and controls. PLoS One, 4(4), e5200, 2009 PMCID:2664471

Mitchell, WM. 18th International Conference on Antiviral Research. Expert Opin Pharmacother, 6(10), 1765-8, 2005 PMCID:2664471

Mitchell, W.M., Blick,G, Strayer,D, Carter,WA and AMP 720 Investigators.. A Phase IIB Prospective, Randomized, Controlled Study Evaluating AMPLIGEN During Structured Treatment Interruption (STI) of HAART in HIV Infection.. Antiviral Res., 57, A41, 2003

Sams, Hunter H, Mitchell, William M, Stratton, Charles W, King, Lloyd E. Culture and immunohistochemical evidence of Chlamydia pneumoniae infection in ulcerative pyoderma gangrenosum. J Am Acad Dermatol, 48(6), 966-9, 2003

Sams,H.H., Mitchell, W.M., Stratton,C.W., and King,L.E.. Culture and Immunochemical Evidence of Chlamydia pneumoniae Infection in Ulcerative Pyoderma Gangrenosum. . J.Am. Acad. Dermatol., 48, 966-969, 2003

Sriram, S., Yao, S., Mitchell, W.M., Calibresi, P., Stratton, C.W., Ikejima, H., and Yamamoto, Y.. Comparative study of the presence of Chalamydia pneumoniae in cerebrospinal fluid from clinically definite and monosymptomatic multiple sclerosis patients. . Clin. Diag. Lab. Immunol., 9, 1332-1337, 2002

King, L E, Stratton, C W, Mitchell, W M. Chlamydia pneumoniae and chronic skin wounds: a focused review. J Investig Dermatol Symp Proc, 6(3), 233-7, 2001

Yao, S Y, Ljunggren-Rose, A, Stratton, C W, Mitchell, W M, Sriram, S. Regulation by IFN-beta of inducible nitric oxide synthase and interleukin-12/p40 in murine macrophages cultured in the presence of Chlamydia pneumoniae antigens. J Interferon Cytokine Res, 21(3), 137-46, 2001

Yao, S Y, Stratton, C W, Mitchell, W M, Sriram, S. CSF oligoclonal bands in MS include antibodies against Chlamydophila antigens. Neurology, 56(9), 1168-76, 2001

Yao, S.-Y., Stratton, C.W., Mitchell, W.M., Sriram, S.. CSF Oligoclonal Bands in Multiple Sclerosis Include Antibodies Against Chlamydophila pneumoniae. . Neurology, 56, 1168-1176, 2001

Vannucci, S A, Mitchell, W M, Stratton, C W, King, L E. Pyoderma gangrenosum and Chlamydia pneumoniae infection in a diabetic man: pathogenic role or coincidence. J Am Acad Dermatol, 42(2 Pt 1), 295-7, 2000

Sriram, S, Stratton, C W, Yao, S, Tharp, A, Ding, L, Bannan, J D, Mitchell, W M. Chlamydia pneumoniae infection of the central nervous system in multiple sclerosis. Ann Neurol, 46(1), 6-14, 1999

Shiram, S., Stratton, C.W., Yao, S., Tharp, A., Ding, L., Bannan, J.D., and Mitchell, W.M. Chlamydia pneumoniae Infection of the Central Nervous System in Multiple Sclerosis. Annals Neurol.46:6-14 (1999).

Mitchell, W M, Ding, L, Gabriel, J. Inactivation of a common epitope responsible for the induction of antibody-dependent enhancement of HIV. AIDS, 12(2), 147-56, 1998

Mitchell, W.M., Ding, L., and Gabriel, J. Inactivation of a common epitope responsible for the induction of antibody- dependent enhancement of the Human Immunodeficiency Virus. AIDS , 12, 147-156, 1998

Sriram, S., Mitchell, W.M., and Stratton, C.W. Multiple sclerosis associated with Chlamydia pneumoniae infection of the central nervous system. Neurology, 50, 571-572, 1998

Robinson, Jr., W.E., Cordeiro, M., Abdel-Malek, S., Qi, J., Chow, S.A., Reinecke, M.G., and Mitchell, W.M. Dicaffeoylquinic acid inhibitors of human immunodeficiency virus (HIV) integrase: Inhibition of the core catalytic domain of HIV integrase. Mol. Pharmacol., 50, 846-855, 1996

Mitchell, W M, Rosenbloom, S T, Gabriel, J. Induction of mucosal anti-HIV antibodies by facilitated transfection of airway epithelium with lipospermine/DNA complexes. Immunotechnology, 1(3-4), 211-9, 1995

Mitchell, W M, Torres, J, Johnson, P R, Hirsch, V, Yilma, T, Gardner, M B, Robinson, W E. Antibodies to the putative SIV infection-enhancing domain diminish beneficial effects of an SIV gp160 vaccine in rhesus macaques. AIDS, 9(1), 27-34, 1995

Mitchell, W.M., Torres, J., Johnson, P.R., Hirsch, V., Yilma, T., Gardner, M.B., and Robinson, Jr., W.E. An animal model for antibody-dependent enhancement of HIV infection: Antibodies to the putative SIV infection-enhancing domain diminish beneficial effects of an SIV gp160 vaccine in Rhesus macaques. AIDS, 9, 27-34, 1995

Crouse, J A, Mitchell, W M. Interferon-gamma receptor: mRNA half-life, receptor mass, and abundance on A431 human epidermoid carcinoma cells. J Interferon Res, 12(1), 23-5, 1992

Robinson, W E, Gorny, M K, Xu, J Y, Mitchell, W M, Zolla-Pazner, S. Two immunodominant domains of gp41 bind antibodies which enhance human immunodeficiency virus type 1 infection in vitro. J Virol, 65(8), 4169-76, 1991 PMCID:248851

Montefiori, D C, Robinson, W E, Hirsch, V M, Modliszewski, A, Mitchell, W M, Johnson, P R. Antibody-dependent enhancement of simian immunodeficiency virus (SIV) infection in vitro by plasma from SIV-infected rhesus macaques. J Virol, 64(1), 113-9, 1990 PMCID:249059

Montefiori, D C, Robinson, W E, Hirsch, V M, Modliszewski, A, Mitchell, W M, Johnson, P R. Antibody-dependent enhancement of SIV infection: further characterization and cross reactivity between macaque and sooty mangabey isolates. J Med Primatol, 19(3-4), 269-78, 1990

Montefiori, D C, Robinson, W E, Modliszewski, A, Mitchell, W M. Effective inactivation of human immunodeficiency virus with chlorhexidine antiseptics containing detergents and alcohol. J Hosp Infect, 15(3), 279-82, 1990

Montefiori, D C, Robinson, W E, Modliszewski, A, Rowland, J M, Schuffman, S S, Mitchell, W M. Differential inhibition of HIV-1 cell binding and HIV-1-induced syncytium formation by low molecular weight sulphated polysaccharides. J Antimicrob Chemother, 25(3), 313-8, 1990

Robinson, W E, Kawamura, T, Gorny, M K, Lake, D, Xu, J Y, Matsumoto, Y, Sugano, T, Masuho, Y, Mitchell, W M, Hersh, E. Human monoclonal antibodies to the human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein gp41 enhance HIV-1 infection in vitro. Proc Natl Acad Sci U S A, 87(8), 3185-9, 1990 PMCID:53860

Robinson, W E, Kawamura, T, Lake, D, Masuho, Y, Mitchell, W M, Hersh, E M. Antibodies to the primary immunodominant domain of human immunodeficiency virus type 1 (HIV-1) glycoprotein gp41 enhance HIV-1 infection in vitro. J Virol, 64(11), 5301-5, 1990 PMCID:248578

Robinson, W E, Mitchell, W M. Neutralization and enhancement of in vitro and in vivo HIV and simian immunodeficiency virus infections. AIDS, 4 Suppl 1, S151-62, 1990

Robinson, W E, Montefiori, D C, Mitchell, W M. Complement-mediated antibody-dependent enhancement of HIV-1 infection requires CD4 and complement receptors. Virology, 175(2), 600-4, 1990

Montefiori, D C, Pellegrino, M G, Robinson, W E, Engle, K, Field, M, Mitchell, W M, Gillespie, D H. Inhibition of HIV-1 proviral DNA synthesis and RNA accumulation by mismatched dsRNA. Biochem Biophys Res Commun, 158(3), 943-50, 1989

Montefiori, D C, Robinson, W E, Mitchell, W M. Antibody-independent, complement-mediated enhancement of HIV-1 infection by mannosidase I and II inhibitors. Antiviral Res, 11(3), 137-46, 1989

Montefiori, D C, Robinson, W E, Mitchell, W M. In vitro evaluation of mismatched double-stranded RNA (ampligen) for combination therapy in the treatment of acquired immunodeficiency syndrome. AIDS Res Hum Retroviruses, 5(2), 193-203, 1989

Montefiori, D C, Sobol, R W, Li, S W, Reichenbach, N L, Suhadolnik, R J, Charubala, R, Pfleiderer, W, Modliszewski, A, Robinson, W E, Mitchell, W M. Phosphorothioate and cordycepin analogues of 2',5'-oligoadenylate: inhibition of human immunodeficiency virus type 1 reverse transcriptase and infection in vitro. Proc Natl Acad Sci U S A, 86(18), 7191-4, 1989 PMCID:298022

Robinson, W E, Montefiori, D C, Gillespie, D H, Mitchell, W M. Complement-mediated, antibody-dependent enhancement of HIV-1 infection in vitro is characterized by increased protein and RNA syntheses and infectious virus release. J Acquir Immune Defic Syndr, 2(1), 33-42, 1989

Robinson, W E, Montefiori, D C, Mitchell, W M, Prince, A M, Alter, H J, Dreesman, G R, Eichberg, J W. Antibody-dependent enhancement of human immunodeficiency virus type 1 (HIV-1) infection in vitro by serum from HIV-1-infected and passively immunized chimpanzees. Proc Natl Acad Sci U S A, 86(12), 4710-4, 1989 PMCID:287341

Montefiori, D C, Robinson, W E, Mitchell, W M. Mismatched dsRNA (ampligen) induces protection against genomic variants of the human immunodeficiency virus type 1 (HIV-1) in a multiplicity of target cells. Antiviral Res, 9(1-2), 47-55, 1988

Montefiori, D C, Robinson, W E, Mitchell, W M. Role of protein N-glycosylation in pathogenesis of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A, 85(23), 9248-52, 1988 PMCID:282716

Montefiori, D C, Robinson, W E, Schuffman, S S, Mitchell, W M. Evaluation of antiviral drugs and neutralizing antibodies to human immunodeficiency virus by a rapid and sensitive microtiter infection assay. J Clin Microbiol, 26(2), 231-5, 1988 PMCID:266258

Robinson, W E, Mitchell, W M, Chambers, W H, Schuffman, S S, Montefiori, D C, Oeltmann, T N. Natural killer cell infection and inactivation in vitro by the human immunodeficiency virus. Hum Pathol, 19(5), 535-40, 1988

Robinson, W E, Montefiori, D C, Mitchell, W M. Antibody-dependent enhancement of human immunodeficiency virus type 1 infection. Lancet, 1(8589), 790-4, 1988

Montefiori, D C, Mitchell, W M. Persistent coinfection of T lymphocytes with HTLV-II and HIV and the role of syncytium formation in HIV-induced cytopathic effect. Virology, 160(2), 372-8, 1987

Robinson, W E, Montefiori, D C, Mitchell, W M. A human immunodeficiency virus type 1 (HIV-1) infection-enhancing factor in seropositive sera. Biochem Biophys Res Commun, 149(2), 693-9, 1987

Robinson, W E, Montefiori, D C, Mitchell, W M. Evidence that mannosyl residues are involved in human immunodeficiency virus type 1 (HIV-1) pathogenesis. AIDS Res Hum Retroviruses, 3(3), 265-82, 1987

Breau, A P, Field, L, Mitchell, W M. Thiono compounds. 4. In vitro mutagenic and antineoplastic activity of TEPA and thio-TEPA. Cell Biol Toxicol, 1(1), 21-30, 1984


Postdoctoral Position Available
no

Postdoctoral Position Details
N/A

Updated Date
02/27/2011