CURRICULUM VITAE

 

CHARLES WILLIAMS FLEXNER

 

Current Appointments:

 

University

 

Professor of Medicine (Clinical Pharmacology and Infectious Diseases), The Johns Hopkins University School of Medicine. Appointment effective 6/1/05.

 

Professor of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine. Appointment effective 6/1/05.

 

Professor of International Health, The Johns Hopkins University, Bloomberg School of Public Health.  Appointment effective 6/1/05.

 

Associate Vice Chair for Academic Fellowship Programs, Department of Medicine, The Johns Hopkins University School of Medicine. Appointment effective 1/1/03.

 

Associate Director, Interschool Graduate Training Program in Clinical Investigation, The Johns Hopkins University School of Medicine and Bloomberg School of Public Health. Appointment effective 7/1/92.

 

Associate Director, General Clinical Research Center, The Johns Hopkins University School of Medicine. Appointment effective 3/1/03.

 

Principal Investigator, The Johns Hopkins University AIDS Clinical Trials Unit. Appointment effective 9/1/00.

 

Hospital

 

Medical Staff, The Johns Hopkins Hospital. Appointment effective 7/1/89.

 

Personal Data:

 

Business Address:

Osler 503

The Johns Hopkins Hospital

600 N. Wolfe Street

Baltimore, MD 21287-5554

Phone:  410-955-9712

Fax: 410-614-9978

e-mail: flex@jhmi.edu

 

Education and Training:

 

                                    Degrees/Year   Institution                                              Discipline

 

Undergraduate: B.S., 1978       Stanford University                               Biology

 

Graduate:                     M.D., 1982      The Johns Hopkins University   Medicine

                                                            School of Medicine

 

Internship:                     1982-1983       Stanford University Hospital                  Medicine

 

Residency:                    1983-1985       Stanford University Hospital                  Medicine

 

Laboratory

Fellowship:                   1985-1988       Laboratory of Viral Diseases                 Virology

                                                            National Institute of Allergy and Infectious Diseases

                                                            National Institutes of Health                 

Clinical

Fellowship:                   1988-1989       The Johns Hopkins University   Infectious Diseases/

                                                            School of Medicine                               Clinical Pharmacology

                                                            Department of Medicine                      

                                                            Infectious Diseases and Clinical Pharmacology

 

Previous Professional Experience:

 

Dates               Position                                                            Institution

 

1996-2005       Associate Professor of Medicine                       The Johns Hopkins University

                           (Clinical Pharmacology                                  School of Medicine

                           and Infectious Diseases)

                        Associate Professor of Pharmacology and Molecular Sciences

                                Associate Professor of International Health        Bloomberg School of Public Health

 

1989-1996             Assistant Professor of Medicine                        The Johns Hopkins University

                           (Clinical Pharmacology                                  School of Medicine

                           and Infectious Diseases)

                        Assistant Professor of Pharmacology and Molecular Sciences

 

1990-1996       Assistant Professor of International Health         The Johns Hopkins University

                                                                                                School of Hygiene and Public Health

 

1998-2003             Assistant Director                                             The Johns Hopkins University

                        General Clinical Research Center                      School of Medicine

 

 

RESEARCH ACTIVITIES

 

Publications:

 

Peer-Reviewed Original Research Articles:

 

1.      Gerkens JF, Flexner C, Oates JA, Shand DG. Prostaglandin and histamine involvement in the gastric vasodilator action of pentagastrin. J Pharm Exptl Ther 1977; 201: 421‑426.

 

2.      Gerkens JF, Shand DG, Flexner C, Nies AS, Oates JA, Data JL. Effect of indomethacin and aspirin on gastric blood flow and acid secretion. J Pharm Exptl Ther 1977; 203: 646‑652.

 

3.      Flexner C, Weiner JP, Saudek CD, Dans PE. Repeated hospitalization for diabetic ketoacidosis: the game of "Sartoris." Am J Med 1984; 76: 691‑695.

 

4.      Flexner C, Hugin A, Moss B. Prevention of vaccinia virus infection in immunodeficient mice by vector‑directed IL‑2 expression. Nature 1987; 330: 259‑262.

 

5.      Walker BD, Flexner C, Paradis TJ, Fuller TC, Hirsch MS, Schooley RT, Moss B. HIV‑1 polymerase is a target for cytotoxic T lymphocytes in infected individuals. Science 1988; 240: 64‑66.

 

6.      Flexner C, Murphy BR, Rooney JF, Wohlenberg C, Yuferov V, Notkins AL, Moss B. Successful vaccination with a polyvalent live vector despite existing immunity to an expressed antigen. Nature 1988; 335: 259‑262.

 

7.      Flexner C, Broyles S, Earl P, Chakrabarti S, Moss B. Characterization of human immunodeficiency virus gag/pol gene products expressed by recombinant vaccinia viruses.  Virology 1988; 166: 339‑349. 

 

8.      Walker BD, Flexner C, Birch-Limberger K, Fisher L, Paradis TJ, Aldovini A, Young R, Moss B, Schooley RT. Long‑term culture and fine specificity of human cytotoxic T lymphocyte clones reactive with HIV-1. Proc Natl Acad Sci USA 1989; 86: 9514-9518.         

 

9.      Lorentsen KJ, Hendrix CW, Collins JM, Kornhauser DM, Petty BG, Klecker RW, Flexner C, Eckel RH, Bartlett JG, Lietman PS. Dextran sulfate is poorly absorbed after oral administration. Ann Intern Med 1989; 111: 561-566.

 

10.  Flexner C, Moss B, London WT, Murphy BR. Attenuation and immunogenicity in primates of vaccinia virus recombinants expressing human interleukin‑2. Vaccine 1990; 8: 17-21.

 

11.  Polydefkis M, Koenig S, Flexner C, Obah E, Gebo K, Chakrabarti S, Earl P, Moss B, Siliciano R. Anchor sequence-dependent processing of human immunodeficiency virus 1 envelope glycoprotein gp160 for CD4+ T cell recognition. J Exp Med 1990; 171: 875-887.

 

12.  Hosmalin A, Clerici M, Houghten R, Pendleton CD, Flexner C, Lucey DR, Moss B, Germain RN, Shearer GM, Berzofsky JA. An epitope in HIV-1 reverse transcriptase recognized by both mouse and human cytotoxic T lymphocytes. Proc Natl Acad Sci USA 1990; 87: 2344-2348.

 

13.  Flexner, C, Barditch-Crovo P, Kornhauser DM, Farzadegan H, Nerhood L, Bell K, Hendrix C, Lorentsen K, Chaisson R, Petty BG, Lietman PS. Pharmacokinetics, toxicity, and activity of intravenous dextran sulfate in human immunodeficiency virus infection. Antimicrob Agents Chemother 1991; 35: 2544-2550.

 

14.  McEntee MF, Sharma DP, Zink MC, Adams RJ, Flexner C, Clements JE, Narayan O. Rhesus monkey macrophages infected with simian immunodeficiency virus cause rapid lysis of CD4-bearing lymphocytes. J Gen Virol 1991; 72; 317-324.

 

15.  Moore RD, Kessler H, Richman DD, Flexner C, Chaisson RE. Non-Hodgkin lymphoma in patients with advanced HIV infection treated with zidovudine. JAMA 1991; 265: 2208-2211.

 

16.  Flexner C, Hildreth JE, Kuncl RW, Drachman DB. 3-deaza-adenosine and inhibition of human immunodeficiency virus. Lancet 1992; 339: 438.

 

17.  Hugin A, Flexner C, Moss B. Clearance of recombinant vaccinia virus expressing interleukin-2: role of local host immune responses. Cell Immunol 1993; 152: 499-509.

 

18.  McEntee MF, Flexner C, Farzadegan H, Pitha P, Narayan O. Comparison of the effects of 3'-azidothymidine with those of neutralizing antibodies on simian immunodeficiency virus infection in macrophages. Antimicrob Agents Chemother 1993; 37: 360-362.

 

19.  Flexner C, van der Horst C, Jacobson M, Powderly W, Barditch-Crovo P, Petty BG, Ganes D, Yacobi A, Duncanson F, DesJardins R, Norden C, Polsky B. Relationship between plasma concentrations of 3'-deoxy-3'-fluorothymidine (alovudine) and antiretroviral activity in two concentration-controlled trials. J Infect Dis 1994 ; 170: 1394-1403.

 

20.  Hendrix CW, Flexner C, Szebeni J, Kuwahara S, Pennypacker S, Weinstein J, Lietman PS. Dipyridamole's effect on zidovudine pharmacokinetics and short-term tolerance in asymptomatic HIV-infected subjects. Antimicrob Agents Chemother 1994; 38: 1036-1040.

 

21.  Petty BG, Cornblath DR, Adornato BT, Chaudhry V, Flexner C, Wachsman M, Sinicropi D, Burton LE, Peroutka SJ. The effect of systemically administered recombinant human nerve growth factor in healthy human subjects. Ann Neurol 1994; 36: 244-246.

 

22.  Dezube B, Lederman M, Spritzler J, Chapman B, Korvick J, Flexner C, Dando S, Mattiacci M, Ahlers C, Zhang L, Novick W, Kasdan P, Fahey J, Pardee A, Crumpacker C. High-dose pentoxifylline in patients with AIDS: Inhibition of TNF production. J Infect Dis 1995; 171: 1628-1632.

 

23.  Haubrich, RH, Flexner C, Lederman MM, Hirsch M, Pettinelli CP, Ginsberg R, Lietman P, Hamzeh FM, Spector S, Richman DD, for the ACTG 213 Team. A randomized trial of the activity and safety of Ro 24-7429 (tat antagonist) versus nucleoside for HIV infection. J Infect Dis 1995; 172: 1246-1252.

 

24.  Chavan SJ, Bornmann WG, Flexner C, Prochaska HJ. Inactivation of human immunodeficiency virus type 1 reverse transcriptase by oltipraz: evidence for formation of a stable adduct. Arch Biochem Biophys 1995; 324: 143-152.

 

25.  Tosi P-F, Schwartz D, Sharma U, Mouneimne Y, Hannig J, Li G, McKinley G, Grieco M, Flexner C, Lazarte J, Norse D, Nicolau C, Volsky DJ. Human erythrocytes bearing electroinserted CD4 neutralize infection in vitro by primary isolates of human immunodeficiency virus type 1. Blood 1996; 87: 4839-4844.

 

26.  Heldman AW, Hartert TV, Daoud EG, Kowalski TE, Pompili VJ, Ray SC, Sisson SD, Tidmore WC, vom Eigen KA, Lietman PS, Petty BG, Flexner C. Oral antibiotic treatment of right-sided staphylococcal endocarditis in intravenous drug-users: prospective randomized comparison with parenteral therapy. Am J Med 1996; 101: 68-76.

 

27.  Vinetz JM, Glass GE, Flexner CE (sic), Mueller P, Kaslow DC. Sporadic urban leptospirosis. Ann Intern Med 1996; 125: 794-798.

 

28.  Fischl MA, Richman DD, Flexner C, Para MF, Haubrich R, Yeramian P, Karim A, Holden-Wiltse J, Meehan P. Phase I study of the toxicity, pharmacokinetics, and activity of the HIV protease inhibitor SC-52151. J Acq Immunodef Syndr 1997; 15: 28-34.

 

29.  Sharma UK, Song HF, Willingham FF, Hannig J, Flexner C, Farzadegan H, Nicolau C,     Schwartz DH. Diagnosis of human immunodeficiency virus infection using citrated whole blood. Clin Diag Lab Immunol 1997; 4: 261-263.

 

30.  Yu X-F, Dawson L, Tian C-J, Flexner C, Dettenhofer M. Mutations of the human immunodeficiency virus type 1 p6Gag domain result in reduced retention of Pol proteins during virus assembly. J Virol 1998; 72: 3412-3417.

 

31.  Lucas G, Lechtzin N, Puryear W, Yau L, Flexner CW, Moore RD. Vancomycin-resistant and vancomycin-sensitive enterococcal bacteremia: a comparison of clinical features and outcomes. Clin Infect Dis 1998; 26: 1127-1133.

 

32.  Barditch-Crovo P, Trapnell CB, Ette E, Zacur H, Coresh J, Rocco LE, Hendrix C, Flexner C. Comparison of the effects of rifampin and rifabutin on the pharmacokinetics and pharmacologic effects of a combined oral contraceptive. Clin Pharmacol Ther 1999; 65: 428-38.

 

33.  Finzi D, Blankson J, Siliciano JD, Margolick JB, Chadwick K, Pierson T, Smith K, Lisziewicz J, Lori F, Flexner C, Quinn TC, Chaisson RE, Rosenberg E, Walker B, Gange S, Gallant J, Siliciano RF. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nature Med 1999; 5: 512-517.

 

34.  Turchin A, Lehmann HP, Flexner CW, Hendrix CW, Shatzer JH, Merz WG. Active Learning Centre: Potential uses and efficacy of an interactive Internet-based teaching tool. Medical Teacher 2000; 22: 271-275.

 

35.  Speck RR, Flexner C, Tian C-J, Yu X-F. Comparison of human immunodeficiency virus type 1 Pr55Gag and Pr160Gag-Pol processing intermediates that accumulate in primary and transformed cells treated with peptidic and non-peptidic protease inhibitors. Antimicrob Agents Chemother 2000; 44: 1397-1403.

 

36.  Hendrix CW, Flexner C, MacFarland RT, Fuchs EJ, Redpath E, Bridger G, Henson GW. Pharmacokinetics and safety of AMD-3100, a novel antagonist of the CXCR-4 chemokine receptor, in human volunteers. Antimicrob Agents Chemother 2000; 44: 1667-1673.

 

37.  Raines CP, Flexner C, Sun E, Heath-Chiozzi M, Lewis RH, Fields C, Deetz C, Apuzzo A, Eshleman SH, Jackson JB, Gallant JE. Safety, tolerability, and antiretroviral effects of ritonavir-nelfinavir combination therapy administered for 48 weeks. J Acquir Immune Defic Syndr 2000;25: 322-328.

 

38.  Dowell P, Flexner C, Kwiterovich PO, Lane MD. Suppression of preadipocyte differentiation and promotion of adipocyte death by HIV protease inhibitors. J Biol Chem 2000; 275: 41325-41332.

 

39.  Flexner CW, Cargill VA, Sinclair J, Kresina TF, Cheever L. Alcohol use can result in enhanced drug metabolism in HIV pharmacotherapy. AIDS Patient Care STDS 2001; 15: 57-58.

 

40.  JG Gerber, S Rosenkranz, Y Segal, J Aberg, R D’Amico, D Mildvan, R Gulick, V Hughes, C Flexner, F Aweeka, A Hsu, J Gal, for the ACTG 401 Study Team. The effect of ritonavir/saquinavir on stereospecific pharmacokinetics of methadone in HIV-infected, methadone using subjects: results of ACTG 401. J Acquir Immune Defic Syndr 2001; 27: 153-160.

 

41.  Ratner L, Lee J, Tang S, Redden D, Hamzeh F, Herndier B, Scadden D, Kaplan L, Ambinder R, Levine A, Harrington W, Grochow L, Flexner C, Tan B, Straus D, for the AIDS Malignancy Consortium. Chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma in combination with highly active antiretroviral therapy. J Clin Oncol 2001; 19: 2171-2178.

 

42.  Speck RR, Yu X-F, Hildreth, JE, Flexner C. Differential effects of P-glycoprotein and multidrug resistance protein-1 on productive HIV infection. J Infect Dis 2002; 186: 332-340.

 

43.  Lucas GM, Flexner CW, Moore RD. Directly administered antiretroviral therapy in the treatment of HIV infection: benefit or burden? AIDS Patient Care STDS 2002; 16: 527-535.

 

44.  Lu J-F , TF Blaschke, C Flexner, S Rosenkranz, LB Sheiner. Model-based analysis of the pharmacokinetic interactions between ritonavir, nelfinavir, and saquinavir after simultaneous and staggered oral administration. Drug Metab Dispos 2002; 30: 1455-1461.

 

45.  Kresina TF, Flexner CW, Sinclair J, Correia MA, Stapleton JT, Adeniyi-Jones S, Cargill V, Cheever LW. Alcohol use and HIV pharmacotherapy. AIDS Res Hum Retroviruses 2002; 18: 757-770.

 

46.  Hamzeh FM, Benson C, Gerber J, Currier J, McCrea J, Deutsch P, Ruan P, Wu H, Lee J, Flexner C, for the AIDS Clinical Trials Group 365 Study Team. Steady-state pharmacokinetic interaction of modified-dose indinavir and rifabutin. Clin Pharmacol Ther 2003; 73: 159-69.

 

47.  Washington CB, Flexner C, Sheiner LB, Rosenkranz SL, Segal Y, Aberg JA, Blaschke TF, for the ACTG 378 Study Team. Effect of simultaneous versus staggered dosing on pharmacokinetic interactions of protease inhibitors. Clin Pharmacol Ther 2003; 73: 406-416.

 

48.  Benson CA, Williams PL, Currier JS, Holland F, Mahon L, Hojczyk P, MacGregor RR, Inderlied C, Flexner C, Neidig J, Chaisson R, Notario GF, Hafner R, for the ACTG 223 Protocol Team. A prospective, randomized trial comparing the efficacy and safety of clarithromycin in combination with either ethambutol, rifabutin or both for the treatment of disseminated Mycobacterium avium complex (MAC) disease in persons with AIDS. Clin Infect Dis 2003; 37: 1234-1243.

 

49.  Rufo P, Lin PW, Andrade A, Jiang L, Rameh L, Flexner C, Alper SL, Lencer WI. Diarrhea-associated HIV-1 aspartyl protease-inhibitors potentiate muscarinic activation of Cl- secretion by T84 cells via prolongation of cytosolic Ca2+ signaling. Am J Physiol Cell Physiol 2004; 286: 998-1008.

 

50.  Hendrix CW, Collier AC, Lederman MM, Schols D, Pollard RB, Brown S, Jackson JB, Coombs RW, Glesby MJ, Flexner CW, Bridger GJ, Badel K, MacFarland RT, Henson GW, Calandra G, for the AMD3100 Study Group. Safety, pharmacokinetics, and antiviral activity of AMD3100, a selective CXCR4 receptor inhibitor, in HIV-1 infection. J Acq Immunodef Syndr 2004; 37: 1253-1262.

 

51.  Frank I, Bosch RJ, Fiscus S, Valentine F, Flexner C, Segal Y, Ruan P, Gulick R, Wood K, Estep S, Fox L, Nevin T, Stevens M, Eron JJ, for the ACTG 307 Protocol Team. Activity, safety, and immunologic effects of hydroxyurea added to didanosine in antiretroviral naïve and experienced HIV-1 infected subjects: a randomized, placebo-controlled trial, ACTG 307. AIDS Res Hum Retroviruses 2004; 20: 916-926.

 

52.  Nettles RE, Kieffer TL, Kwon P, Monie D, Han Y, Adnan S, Parsons T, Cofrancesco J, Gallant JE, Quinn T, Jackson B, Flexner C, Carson K, Ray S, Persaud D, Siliciano RF. Intermittent HIV-1 viremia  and the evolution of drug resistance in patients on highly active antiretroviral therapy. JAMA 2005; 293: 817-829.

 

53.  Nettles RE, Kieffer TL, Cofrancesco J, Gallant JE, Quinn T, Jackson B, Flexner C, Carson K, Wu A, Siliciano RF. Psychological distress and physical pain appear to have no short-term adverse impact on plasma HIV-1 RNA levels in patients on successful HAART. HIV Clin Trials 2005; in press.

 

54.  Nettles RE, Kieffer TL, Parsons T, Johnson J, Cofrancesco J, Gallant JE, , Carson K, Siliciano RF, Flexner C. Marked intraindividual variability in antiretroviral concentrations may limit the utility of therapeutic drug monitoring. Clin Infect Dis 2006; in press.

 

 

Review Articles:

 

55.  Flexner C, Perlroth MG. Cyclosporine ‑ a powerful new immunosuppressant. Western J Med 1985; 143: 92‑93.

 

56.  Moss B, Flexner C. Vaccinia virus expression vectors. Ann Rev Immunol 1987; 5: 305‑324.

 

57.  Moss B, Fuerst T, Flexner C, Hugin A. Roles of vaccinia virus in the development of new vaccines. Vaccine 1988; 6: 161‑163.

 

58.  Moss B, Flexner C. Vaccinia virus expression vectors. Annals NY Acad Sci 1989; 569: 86-103.

 

59.  Flexner C. New Approaches to Vaccination. Adv Pharmacol 1990; 21: 51-99.

 

60.  Flexner C. Management of occupational exposure to HIV: an update. AIDS Med Report 1991; 4: 13-20.

 

61.  Flexner C. New antiretroviral agents in clinical development. Curr Opin Infect Dis 1992; 5: 798-805.

 

62.  Piscitelli SC, Flexner C, Minor JR, Polis MA, Masur H. Drug interactions in HIV-infected patients. Clin Infect Dis 1996; 23: 685-693.

 

63.  Flexner C. Pharmacokinetics and pharmacodynamics of HIV protease inhibitors. Infect Med 1996; 13 (Suppl. F): 16-23.

 

64.  Flexner C. Drug interactions. PRN Notebook 1997; 2 (1): 24-29.

 

65.  Flexner C. Principles of clinical pharmacology in post-exposure prophylaxis. Am J Med 1997; 102 (Suppl 5B): 32-38.

 

66.  Pham PA, Flexner C. Antiretroviral drug interactions in the HIV-infected patient. HIV Advances in Research and Therapy 1997; 7 (2): 10-17.

 

67.  Flexner C. HIV-protease inhibitors. New Engl J Med 1998; 338: 1281-1292.

 

68.  Maenza J, Flexner C. Combination antiretroviral therapy for HIV infection. Amer Family Physician 1998; 57: 2789-2798.

 

69.  Flexner C. Drug-drug interactions in the HIV-infected patient. Improving Management of HIV Disease, 1998; 6 (2): 31-36.

 

70.  Flexner C. Understanding and managing drug interactions. PRN Notebook 1998; 3 (3): 9-15.

 

71.  Flexner C. Double jeopardy: the hazards of drug-drug interactions. HIV Research Initiatives and Treatment 1998; 4: 3-8.

 

72.  Flexner C. Fat city: understanding HIV lipodystrophy. Hopkins HIV Report 1998; 10: 14-15.