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Biography of Konstance K. Knox, Ph.D.

Director of Research, Wisconsin Viral Research Group
Email: kknox@wisconsinlab.com

Dr. Knox received her Bachelor's degree in Medical Laboratory Sciences from Marquette University in 1977 and became board certified by the American Society of Clinical Pathologists that same year. While working as a Research Technologist in the 1980's Dr. Knox gained experience with a variety of microbial research systems and with the scientific publication process (1,2). In 1987 she joined the laboratory of Donald Carrigan, Ph.D. as a Senior Research Technologist and began her career in viral pathogenesis. In this position Dr. Knox was an active participant in a number of virologically related projects and gained a basic understanding of the nature of virally related diseases and broad experience in both clinical and basic virology (3-10). At the same time she became interested in laboratory management and business and received a Master's degree in business management from Cardinal Stritch University in 1990. In 1992 Dr. Knox entered the graduate program of the Department of Pathology of the Medical College of Wisconsin as a doctoral student in the laboratory of Dr. Carrigan. Her previous experience with HIV (4) and the newly identified human herpesvirus six (HHV-6) (4,6,10) led her to choose to investigate the pathogenetic interactions between HIV and HHV-6 as her doctoral dissertation research project. The project proved to be both interesting and successful (11-15), and she received her doctoral degree in 1994. Her doctoral dissertation (16) was named as the Outstanding Doctoral Dissertation by the Medical College of Wisconsin in 1995. Also, Dr. Knox's work on the role of human herpesvirus six (HHV-6) in chronic diseases also led her to be named the 1995 Distinguished Alumna of the Program in Medical Laboratory Sciences at Marquette University.

After receiving her degree, Dr. Knox chose to broaden her scientific horizons by taking a post-doctoral position as a Senior Research Associate in the Immunotherapy and Gene Therapy Research and Treatment Institute at St. Luke's Medical Center in Milwaukee. The Institute was a translational medical research program aimed at developing methods of enhancing immunologic killing of specific forms of cancer. Dr. Knox's work centered upon the design and development of bispecific monoclonal antibodies (BsAb) that combined an anti T lymphocyte antibody (CD3 specific) with a tumor specific antibody (e.g. carcinoembryonic antigen). After treatment with the BsAb antibodies activated T lymphocytes (ATL) of widely different specificities would then recognize and bind to and kill tumor cells. In addition the cytotoxicity potential of the (ATC) was enhanced by transducing them with a Moloney murine retrovirus vector carrying the human interleukin one beta (IL-1B) gene that expressed high levels of the cytotoxic IL-1B protein. The BsAb would bring the T lymphocytes in very close proximity to the tumor cells which provided an enhancement of the Il-1B mediated killing (17).

Following her post-doctoral fellowship, Dr. Knox, in partnership with Dr. Carrigan, established a CLIA certified clinical diagnostic laboratory (Wisconsin Viral Research Group) and a non-profit research institute (Institute for Viral Pathogenesis) in Milwaukee. Her background in business played a vital role in the successes of these endeavors. WVRG specializes in the diagnosis of beta herpesvirus infections in both immunocompromised patients and patients with various chronic diseases. IVP has successfully obtained research grants from major funding organizations for virological studies in patients with multiple sclerosis and chronic fatigue syndrome.

Dr. Knox's research interests have continued to focus upon the role of persistent viral and prion infections in chronic diseases of animals and humans. The patient populations that have served as her research subjects include bone marrow (18,19) and liver transplant recipients (20,21,22,23) patients with AIDS (24), people with multiple sclerosis (25,26,27,28) and chronic fatigue syndrome patients. Dr. Knox has presented numerous invited lectures, primarily involving her work on HHV-6 and has published more than 39 articles describing her research. For the past several years, her work has focused upon the role of HHV-6 in multiple sclerosis (supported by grants from the National Multiple Sclerosis Society) and upon the molecular mechanisms involved in the disease pathogenesis of a subset of patients with chronic fatigue syndrome (funded by grants from the American Association for Chronic Fatigue Syndrome and the National CFIDS Foundation).

Dr. Knox has served as a special reviewer for the National Prion Research Program of the National Institutes of Health and has served as a peer reviewer for several journals and funding agencies. She is a member of the American Society for Microbiology, the Infectious Diseases Society of America, American Association for the Advancement of Science (AAAS), and the Pan American Society for Clinical Virology. She has served on the scientific advisory board of the International Association for Chronic Fatigue Syndrome and also serves as a member of the scientific advisory board of the Wisconsin CFS Association.

Please find more information in Dr. Knox's Biosketch (PDF).

Publications

  1. Komorowski RA, Farmer SG and Knox KK. (1986) Comparison of cerebrospinal fluid C-reactive protein and lactate for diagnosis of meningitis. J Clin Microbiol 24:982-985.
  2. Kehl KS, Farmer SG, Komorowski RA and Knox KK. (1986). Antigenic variation among Borrelia sp in relapsing fever. Infect Immun 54:899-902.
  3. Carrigan DR and Knox KK. (1990). Identification of interferon resistant subpopulations in several strains of measles virus: Positive selection by growth of the virus in brain tissue. J Virol 64:1606-1613.
  4. Carrigan DR, Knox KK, and Tapper MA. (1990). Suppression of human immunodeficiency virus type 1 replication by human herpesvirus six. J Infect Dis 162:844-851
  5. Finkle C, Tapper MA, Knox KK, and Carrigan DR. (1991). Coinfection of cells with human immunodeficiency virus and cytomegalovirus in lung tissue of patients with AIDS. J Acquired Immunodeficiency Syndromes 4:735-737.
  6. Russler SK, Tapper MA, Knox KK, Liepins A, and Carrigan DR. (1991). Pneumonitis associated with coinfection by human herpesvirus six and legionella in an immunocompetent adult. Amer J Pathol 138:1405-1411.
  7. Knox KK, Drobyski WR, and Carrigan DR. (1991). Cytomegalovirus isolate resistant to ganciclovir and foscarnet from a marrow transplant patient. Lancet 337:1292-1293.
  8. Drobyski WR, Gottlieb M, Carrigan DR, Grebenau M, Schram H, Ostberg L, and Ash R. (1991). Phase I study of safety and pharmakinetics of a human anti-cytomegalovirus monoclonal antibody in allogeneic marrow transplant recipients. Transplantation 51:1190-1196.
  9. Drobyski WR, Knox KK, Carrigan DR, and Ash RC. (1991). Foscarnet therapy of ganciclovir resistant cytomegalovirus in marrow transplantation. Transplantation 52:155-157.
  10. Carrigan DR, Drobyski WR, Russler SK, Tapper MA, Knox KK, and Ash RC. (1991). Interstitial pneumonitis associated with human herpesvirus six (HHV-6) infection in marrow transplant patients. Lancet 338:147-149.
  11. Knox KK and Carrigan DR. (1994). Disseminated active HHV-6 infections in patients with AIDS. Lancet 343:577-578.
  12. Knox KK and Carrigan DR. (1994). HHV 6 and CMV pneumonitis in immunocompromised patients. Lancet 343:1647.
  13. Knox KK, Pietryga D, Franciosi R, and Carrigan DR. (1995). Progressive immunodeficiency and fatal pneumonitis associated with HHV 6 infection in an infant. Clin Infect Dis, 20:406-413.
  14. Knox KK and Carrigan DR. (1995). Active human herpesvirus six (HHV 6) infection of the central nervous system in patients with AIDS. J Immune Defic Syndr and Hum Retrovir 9:69-73.
  15. Knox KK, Harrington D and Carrigan DR. (1995). Fulminant human herpesvirus six (HHV 6) encephalitis in an HIV infected infant. J Med Virol, 45:288-292.
  16. Knox KK. Human Herpesvirus Six (HHV-6): Evidence For Its Role as a Cofactor in the Pathogenesis of AIDS. Doctoral Dissertation. Department of Pathology; Medical College of Wisconsin; December, 1994.
  17. Trevor KT, Quinn ER, Sen M, Wankowski D, Knox KK, LeFever AV and Lum LG. (2000). Bispecific antibody reactivation of gene-transduced T cells: implications for cancer immunotherapy and gene therapy. Tumor Targeting 4:245-256.
  18. Knox KK and Carrigan DR. (1996). Chronic marrow suppression in a bone marrow transplant patient associated with persistent HHV 6 marrow infection. Clin Infect Dis, 22:174-175.
  19. Carrigan DR, Knox KK. (1994). Human herpesvirus six (HHV 6) isolation from bone marrow: HHV 6 associated bone marrow suppression in bone marrow transplant patients. Blood, 84:3307-3310.
  20. Carrigan DR and Knox KK. (1999). Pathogenic role of human herpesvirus 6 in transplantation. Curr Opin Organ Transplant, 4:285-291.
  21. Rogers J, Singh N, Carrigan DR, Rohal S, Kusne S, Knox KK, Wagener MM and Fung JJ. (2000). Human herpesvirus 6 in liver transplant recipients: role in pathogenesis of fungal infections, neurologic complications and outcome. Transplantation, 69:2566-2573.
  22. Singh N, Husain S, Carrigan DR, Knox KK, Week KE, Wagener MM and Gayowski T. (2001). Impact of human herpesvirus six viremia on the frequency and severity of recurrent hepatitis C hepatitis in liver transplant recipients. Clin Transpl , 16:92-96.
  23. Singh N, Bentlejewski C, Carrigan DR, Gayowski T, Knox KK and Zeevi A. Persistent lack of human herpesvirus 6 specific T-helper cell responses in liver transplant recipients. (2002). Transpl Infect Dis, 4:59-63.
  24. Knox KK and Carrigan DR. (1996). Active HHV 6 infection in the lymph nodes of HIV infected patients: In vitro evidence that HHV 6 can break HIV latency. J Acquired Immune Defic Syndr and Hum Retrovirol, 11:370-378.
  25. Carrigan DR, Harrington D and Knox KK. (1996). Subacute leukoencephalitis caused by CNS infection with human herpesvirus six manifesting as acute multiple sclerosis. Neurology, 47:145-148.
  26. Carrigan DR and Knox KK. (1997). Human herpesvirus six and multiple sclerosis. Multiple Sclerosis, 3:390 394.
  27. Knox KK, Brewer JH, Harrington DJ, Henry JM, and Carrigan DR. (2000). Human herpesvirus six and multiple sclerosis: systemic active infections in patients with early disease. Clin Infect Dis, 31:894-903.
  28. Knox KK and Carrigan DR. (2001) Active human herpesvirus six viremia in patients with multiple sclerosis. Genes and Viruses in Multiple Sclerosis; Elsevier Science B.V. Amsterdam, The Netherlands, pp:185-194.


Invited Lectureships

"Progressive Immunodeficiency and Fatal Pneumonitis Associated with HHV-6 Infection in an Infant"
Pediatric Grand Rounds, Children's Hospital of Wisconsin; October 1993; Milwaukee, Wisconsin

"Early Reactivation of Human Herpesvirus Six to Productive Infection in HIV Infected Patients"
Annual Meeting of the Tumor Cell Biology Laboratory, National Cancer Institute; September 1994;
Bethesda, Maryland

"Human Herpesvirus Six Infections in HIV Infected Patients"
Infectious Disease Society of Milwaukee; January 1995; Milwaukee, Wisconsin

"Human Herpesvirus Six: Opportunistic Pathogen or Human Immunodeficiency Virus?"
Medical Grand Rounds, St. Luke's Medical Center; November 1995; Milwaukee, Wisconsin

"Human Herpesvirus in AIDS"
ABC Television Network Interview, World News Tonight; December 1995

"Role of HHV-6A as a Cofactor in the Pathogenesis of AIDS"
Symposium on New Concepts in the Pathogenesis of AIDS, Texas Tech University Health Sciences Center; February 1996; Lubbock, Texas

"HHV-6A: Cofactor in the Pathogenesis of AIDS"
Milwaukee AIDS Project; June 1996; Milwaukee, Wisconsin

"Role of HHV-6A in AIDS and Chronic Fatigue Syndrome"
Living Well: Live interview and listener call-in program, WHAD FM, Wisconsin Public Radio; June 1996; Delafield, Wisconsin

"Human Herpesvirus Six: Roles in AIDS and Central Nervous System Disease"
Abbott Laboratories, Pharmaceutical Products Division; October 30, 1996; Abbott Park, Illinois

"Pathogenicity of Human Herpesvirus Six"
GlaxoWellcome Research and Development, Clinical Applications Research, Research Triangle Park; December 9, 1996; North Carolina

“Diagnosis of Herpesvirus Infections of the Central Nervous System”
Wisconsin Virology Conference, Sponsored by the Wisconsin State Laboratory of Hygiene; June 5, 1997; Madison, Wisconsin

“Human Herpesvirus Six and Diseases of the Central Nervous System”
Conference on Infectious Agents, Disorders of Cognitive Function and Molecular Medicine, Sponsored by NeuroimmunoTherapeutics Research Foundation; June 16, 1997; San Francisco, California

“Role of Human Herpesvirus Six in Multiple Sclerosis and Immunohistochemical Staining of Tissues for the Detection of HHV-6 Infected Cells”
Special Seminar and Workshop, Neuroimmunology Branch, National Institutes of Neurological Disease and Stroke,, National Institutes of Health; July 28-29, 1997; Bethesda, Maryland

“HHV6 and Its Relationship to HIV Infection”
Consumer Advisory Panel of the AIDS Resource Center of Wisconsin, March 10, 1998; Milwaukee, Wisconsin

“Active HHV-6 Infections and Chronic Central Nervous System Disease”
Wisconsin Virology Conference, Sponsored by the Wisconsin State Laboratory of Hygiene; June 17, 1998; Madison, Wisconsin

“Human Herpesvirus Six and Multiple Sclerosis”
First Annual Meeting of the Wisconsin Chapter of the Infectious Diseases Society of America; June 26, 1998; Madison, Wisconsin

“Human Herpesvirus Six: A Viral Trigger for Multiple Sclerosis?”
Center for Neurological Disorders; March 12, 1999; St. Francis Hospital, Milwaukee, Wisconsin

“Active Infection of CNS Tissues, Peripheral Blood Leukocytes and Lymphoid Tissues with Human Herpesvirus Six in Patients with Multiple Sclerosis”
24th International Herpesvirus Workshop; July 17, 1999; Boston, Massachusetts

“Candidate Agents in MS: HHV-6"
Symposium on Demonstrating Infectious Cause: Viral and Bacterial Infections in MS and Related Disorders; Sponsored by The National Multiple Sclerosis Society; August 23-25, 1999; Brighton, England

"Human Herpesvirus Six and Multiple Sclerosis: Potential Role as Trigger of the Disease Process"
New York Academy of Sciences; October 20, 1999; New York, New York

“Herpesviruses and Multiple Sclerosis”
European Charcot Foundation Symposium 1999; October 28-30, 1999; Venice, Italy

"HHV-6 Infection Following Bone Marrow and Stem Cell Transplantation"
International Bone Marrow Transplant Registry/ Autologous Blood and Marrow; Transplant Registry Annual Meeting; March 28, 2000; Anaheim, California

"Opportunistic HHV-6 Infections in Adults"
Fourth International Conference on Human Herpesviruses 6, 7 and 8; May 10-12, 2001; Pasteur Institute, Paris, France

"Role of Human Herpesvirus Six in Multiple Sclerosis"
Meeting of the Multiple Sclerosis Association of America; August 2001, Great Falls, Montana
 

Peer Reviewer

The LANCET
Journal of Medical Virology
Blood
Trends in Microbiology
The Wellcome Trust; London, United Kingdom
Clinical Infectious Diseases
Journal of Infectious Diseases