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Department of Pathology, Microbiology, and Immunology

 

 

  William M. Mitchell, M.D., Ph.D.Mitchell, Bill
 

 

  Professor

  Dept of Pathology, Microbiology and Immunology

 

 

  Contact Information
 


   Office Location:

 U-3302 MCN

 Phone: 615-322-3238   

 E-mail: bill.mitchell@vanderbilt.edu

 

 Campus Mail address:

 Pathology, Microbiology and Immunology-3rd Fl

 C-3321 MCN (2561)

 

 US Mailing address:

 Vanderbilt University School of Medicine

 Dept. of Pathology, Microbiology and Immunology

 C-3321 MCN

 Nashville, TN 37232-2561

 

 

 

Education

 

 

PhD, Johns Hopkins
MD, Vanderbilt
BA, Vanderbilt

 

 

Research Keywords

 

 


 

 

Research Description

 

 

Current active areas of investigation include the following:
1. Innate immunity initiated by Activation of Toll-Like Receptor 3 (TLR3). The TLRs are microbial pattern recognition proteins that initiate innate immune responses to microbial invasion. TLR3 is unique among the 10 human TLRs in its intracellular signaling pathways and reduced inflammatory responses. Agonists of TLR3 and response elements are being examined as viral inhibitors and next generation immune vaccine enhancers (super adjuvants) with reduced adverse advents in humans. We have investigated efficacy against highly pathogenic avian influenza viruses in humans (HPIVh) including H5N1 and oseltamivir resistant H7N9 as well as seasonal influenza vaccines with activity against HPIVh.
2. Next Generation Sequencing (NGS) applications. We have used a variety of NGS platforms to develop new diagnostic massively parallel sequencing methods for the real time evaluation of efficacy of cancer therapy using plasma/serum analysis of DNA from apoptotic neoplastic cells.
3. Pathogenesis of human intracellular pathogens. Our current focus is on the pathogenesis of latency of two microorganisms: a) 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. 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. b) Human immunodeficiency virus (HIV) is the etiological agent of the Acquired Immunodeficiency Syndrome (AIDS). Current studies are focused on HIV latency. Latent HIV provirus integrated into the human genome of memory B lymphocytes provide silent sites of reactivation not susceptible to current anti-retroviral therapy (ART). Strategies involve activation of provirus by TLR3 agonists and interferon with ART control of infection to eliminate proviral foci of latent infection.


 

 

Publications

 

 

Mitchell, WM, Nicodemus, CF, Carter, WA, Horvath, JC, Strayer, DR. Discordant biological and toxicological species responses to TLR3 activation. Am J Pathol, 184(4), 1062-72, 2014

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

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

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

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

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

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

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

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

, 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

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

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

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., 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

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

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

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

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, 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, 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

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

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

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

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

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

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

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, 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

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

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

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

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

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

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, 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

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

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. 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