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Tawanda Gumbo, MD

 

Investigator

Director, Center for Infectious Diseases Research and Experimental Therapeutics 

Honorary Professor of Medicine, University of Cape Town, Observatory, South Africa

Adjunct Professor of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas

 

Contact Information

3434 Live Oak St.

Dallas, TX 75204

Tawanda.Gumbo@baylorhealth.edu

 

 

Education

 

Graduate

University of Zimbabwe Medical School, Harare, Zimbabwe

Medical Degree

 

Post Graduate

Case Western Reserve University, Cleveland, Ohio

Residency, Internal Medicine

 

Cleveland Clinic Foundation, Cleveland, Ohio

Fellowship, Infectious Diseases

 

 

 

Major Scientific Contributions to Laboratory and Mathematical Model Design 

 

1.       The hollow fiber model of tuberculosis [“glass mouse”] (2003)

 

Formal qualification approval by the European Medicines Agency (EMA):

http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2015/02/WC500181899.pdf

 

Review by the Food and Drug Administration (FDA) available at http://cid.oxfordjournals.org/content/61/suppl_1/S32.full.pdf+html

 

Papers and summary of model performance and forecasting accuracy:

 

[J Pasipanodya, E. Nuremberger, K. Romero, D. Hanna, T. Gumbo. Systemic analysis of hollow fiber model of tuberculosis experiments. Clin Infect Dis (2015) 61 (suppl 1): S10-S17 (freely available at: http://cid.oxfordjournals.org/content/61/suppl_1/S10.full.pdf+html)

 

T Gumbo, J. G. Pasipanodya, E. Nuremberger, K. Romero, D. Hanna.

Correlations between the hollow fiber model of tuberculosis and therapeutic events in tuberculosis patients: learn and confirm. Clin Infect Dis (2015) 61 (suppl 1): S18-S24 (freely available at:

 http://cid.oxfordjournals.org/content/61/suppl_1/S18.full.pdf+html)

 

T Gumbo, J. G. Pasipanodya, K. Romero, D. Hanna, E. Nuremberger. Forecasting accuracy of the hollow fiber system model of tuberculosis for clinical therapeutic outcomes. Clin Infect Dis (2015) 61 (suppl 1): S25-S31 (freely available at: http://cid.oxfordjournals.org/content/61/suppl_1/S25.full.pdf+html)

 

T Gumbo, Louie A, Deziel MR, Drusano GL. Pharmacodynamic driven dosing of Rifampin in a hollow fiber system model of tuberculosis. (Abstract # A-1156). 43rd Interscience Conference of Antimicrobial Agents and Chemotherapy, Chicago, Ill, September, 2003.]

 

       2.       Candida glabrata murine model of disseminated candidiasis

[T Gumbo, GL Drusano, W Liu, L Ma, MR Deziel, MF Drusano, A Louie. Anidulafungin pharmacokinetics and microbial response in neutropenic mice with disseminated candidiasis. Antimicrobial agents and chemotherapy 50 (11), 3695-3700]

 

3.       Semi-mechanistic systems equations for effect of dynamic antibiotic concentrations against Mycobacterium tuberculosis drug-susceptible and drug-resistant sub-populations.

[T Gumbo, A Louie, MR Deziel, LM Parsons, M Salfinger, GL Drusano. Selection of a moxifloxacin dose that suppresses drug resistance in Mycobacterium tuberculosis, by use of an in vitro pharmacodynamic infection model and mathematical modeling. Journal of Infectious Diseases 190 (9), 1642-1651]

 

4.       A quadratic function for the relationship between drug exposure, resistance emergence, and time.

 

[T Gumbo, CSWS Dona, C Meek, R Leff. Pharmacokinetics-pharmacodynamics of pyrazinamide in a novel in vitro model of tuberculosis for sterilizing effect: a paradigm for faster assessment of new antituberculosis drugs. Antimicrobial agents and chemotherapy 53 (8), 3197-3204]

 

5.       Use of artificial intelligence derived methods to identify (a) role on non-linear interactions of pharmacokinetic, physiological, and pathological factors in patient outcomes in several infectious diseases, and (b) effects of maturation, inflammation, and other physiological factors on pharmacology of small molecules  

 

Major Contributions to Scientific Knowledge

 

1.        Mapping of the human and macaque immunity and Mycobacterium tuberculosis isolates in whole lungs of latent and active tuberculosis disease using next generation sequencing (2013-2015).

  

2.       Fractal geometry effects of obesity on drug pharmacokinetics.

 

Keys papers:

 

[Pasipanodya JP, Hall RG 2nd, Gumbo T. In silico-derived bedside formula for individualized micafungin dosing for obese patients in the age of deterministic chaos. Clin Pharmacol Ther. 2015 Mar;97(3):292-7

 

Hall RG 2nd, Swancutt MA, Meek C, Leff R, Gumbo T. Weight drives caspofungin pharmacokinetic variability in overweight and obese people: fractal power signatures beyond two-thirds or three-fourths. Antimicrob Agents Chemother. 2013 May;57(5):2259-64.

 

 Hall RG 2nd, Swancutt MA, Meek C, Leff RD, Gumbo T. Ethambutol pharmacokinetic variability is linked to body mass in overweight, obese, and extremely obese people. Antimicrob Agents Chemother. 2012 Mar;56(3):1502-7.

 

Hall RG, Swancutt MA, Gumbo T. Fractal geometry and the pharmacometrics of micafungin in overweight, obese, and extremely obese people. Antimicrob Agents Chemother. 2011 Nov;55(11):5107-12.

 

Gumbo T, Hiemenz J, Ma L, Keirns JJ, Buell DN, Drusano GL. Population pharmacokinetics of micafungin in adult patients. Diagn Microbiol Infect Dis. 2008 Mar;60(3):329-31]

  

3.       Pioneered PK/PD of anti-TB drugs and use of pharmacometric optimization of anti-TB drug doses and combinations (2002-2015).

 

Key papers:

 

[Gumbo T, Angulo-Barturen I, Ferrer-Bazaga S. Pharmacokinetic-pharmacodynamic and dose-response relationships of antituberculosis drugs: recommendations and standards for industry and academia. J Infect Dis. 2015 Jun 15;211 Suppl 3:S96-S106.

 

Srivastava S, Sherman C, Meek C, Leff R, Gumbo T. Pharmacokinetic mismatch does not lead to emergence of isoniazid- or rifampin-resistant Mycobacterium tuberculosis but to better antimicrobial effect: a new paradigm for antituberculosis drug scheduling. Antimicrob Agents Chemother. 2011 Nov;55(11):5085-9.

 

Pasipanodya J, Gumbo T. An oracle: antituberculosis pharmacokinetics-pharmacodynamics, clinical correlation, and clinical trial simulations to predict the future. Antimicrob Agents Chemother. 2011 Jan;55(1):24-34

 

Gumbo T, Louie A, Deziel MR, Liu W, Parsons LM, Salfinger M, Drusano GL. Concentration-dependent Mycobacterium tuberculosis killing and prevention of resistance by rifampin. Antimicrob Agents Chemother. 2007 Nov;51(11):3781-8.

 

Gumbo T, Louie A, Liu W, Brown D, Ambrose PG, Bhavnani SM, Drusano GL. Isoniazid bactericidal activity and resistance emergence: integrating pharmacodynamics and pharmacogenomics to predict efficacy in different ethnic populations. Antimicrob Agents Chemother. 2007 Jul;51(7):2329-36.

 

Gumbo T, Louie A, Deziel MR, Drusano GL. Pharmacodynamic evidence that ciprofloxacin failure against tuberculosis is not due to poor microbial kill but to rapid emergence of resistance. Antimicrob Agents Chemother. 2005 Aug;49(8):3178-81]

   

4.       The role of efflux pumps in phenotypic resistance & the antibiotic resistance arrow of time in antituberculosis drugs (2007-2015)

 

Key papers:

 

[Schmalstieg AM, Srivastava S, Belkaya S, Deshpande D, Meek C, Leff R, van Oers NS, Gumbo T. The antibiotic resistance arrow of time: efflux pump induction is a general first step in the evolution of mycobacterial drug resistance. Antimicrob Agents Chemother. 2012 Sep;56(9):4806-15.

 

Pasipanodya JG, Gumbo T. A new evolutionary and pharmacokinetic-pharmacodynamic scenario for rapid emergence of resistance to single and multiple anti-tuberculosis drugs. Curr Opin Pharmacol. 2011 Oct;11(5):457-63.

 

Srivastava S, Musuka S, Sherman C, Meek C, Leff R, Gumbo T. Efflux-pump-derived multiple drug resistance to ethambutol monotherapy in Mycobacterium tuberculosis and the pharmacokinetics and pharmacodynamics of ethambutol. J Infect Dis. 2010 Apr 15;201(8):1225-31.

 

Gumbo T, Louie A, Liu W, Ambrose PG, Bhavnani SM, Brown D, Drusano GL. Isoniazid's bactericidal activity ceases because of the emergence of resistance, not depletion of Mycobacterium tuberculosis in the log phase of growth. J Infect Dis. 2007 Jan 15;195(2):194-201]

  

5.       Overhauled susceptibility breakpoints of anti-tuberculous antibiotics and their determination in tuberculosis, and then validated them (2010-2015).

 

Key papers:

 

[Gumbo T, Pasipanodya JG, Wash P, Burger A, McIlleron H. Redefining multidrug-resistant tuberculosis based on clinical response to combination therapy. Antimicrob Agents Chemother. 2014 Oct;58(10):6111-5.

 

Gumbo T, Chigutsa E, Pasipanodya J, Visser M, van Helden PD, Sirgel FA, McIlleron H. The pyrazinamide susceptibility breakpoint above which combination therapy fails. J Antimicrob Chemother. 2014 Sep;69(9):2420-5.

 

Chigutsa E, Pasipanodya JG, Visser ME, van Helden PD, Smith PJ, Sirgel FA, Gumbo T, McIlleron H. Impact of nonlinear interactions of pharmacokinetics and MICs on sputum bacillary kill rates as a marker of sterilizing effect in tuberculosis. Antimicrob Agents Chemother. 2015 Jan;59(1):38-45.

 

Gumbo T. New susceptibility breakpoints for first-line antituberculosis drugs based on antimicrobial pharmacokinetic/pharmacodynamic science and population pharmacokinetic variability. Antimicrob Agents Chemother. 2010 Apr;54(4):1484-91.]

 

6.       Fractal geometry effects of obesity on drug pharmacokinetics.

 

Keys papers:

 

[Hall RG 2nd, Swancutt MA, Meek C, Leff R, Gumbo T. Weight drives caspofungin pharmacokinetic variability in overweight and obese people: fractal power signatures beyond two-thirds or three-fourths. Antimicrob Agents Chemother. 2013 May;57(5):2259-64.  

 

Jain MK, Pasipanodya JG, Alder L, Lee WM, Gumbo T. Pegylated interferon fractal pharmacokinetics: individualized dosing for hepatitis C virus infection. Antimicrob Agents Chemother. 2013 Mar;57(3):1115-20.

 

 

Hall RG 2nd, Swancutt MA, Meek C, Leff RD, Gumbo T. Ethambutol pharmacokinetic variability is linked to body mass in overweight, obese, and extremely obese people. Antimicrob Agents Chemother. 2012 Mar;56(3):1502-7.

 

Hall RG, Swancutt MA, Gumbo T. Fractal geometry and the pharmacometrics of micafungin in overweight, obese, and extremely obese people. Antimicrob Agents Chemother. 2011 Nov;55(11):5107-12.

 

Gumbo T, Hiemenz J, Ma L, Keirns JJ, Buell DN, Drusano GL. Population pharmacokinetics of micafungin in adult patients. Diagn Microbiol Infect Dis. 2008 Mar;60(3):329-31]

 

7.       PK/PD and dose selection for echinocandins and the concept of intermittent and single-dose dosing for treatment of candidiasis (2002-2015)

 

Key papers:

 

[Gumbo T, Drusano GL, Liu W, Kulawy RW, Fregeau C, Hsu V, Louie A. Once-weekly micafungin therapy is as effective as daily therapy for disseminated candidiasis in mice with persistent neutropenia. Antimicrob Agents Chemother. 2007 Mar;51(3):968-74.

 

Gumbo T. Impact of pharmacodynamics and pharmacokinetics on echinocandin dosing strategies. Curr Opin Infect Dis. 2007 Dec;20(6):587-91.]

  

8.       Established the role of microsporidiosis (Enterocytozoon bieneusi) in AIDS diarrhea (1999), in in transplant patients (1999), and self-limited diarrhea in immunocompetent patients (2000).

 

Key papers:

 

[Gumbo T, Gangaidzo IT, Sarbah S, Carville A, Tzipori S, Wiest PM. Enterocytozoon bieneusi infection in patients without evidence of immunosuppression: two cases from Zimbabwe found to have positive stools by PCR. Ann Trop Med Parasitol. 2000 Oct;94(7):699-702

 

Gumbo T, Sarbah S, Gangaidzo IT, Ortega Y, Sterling CR, Carville A, Tzipori S, Wiest PM. Intestinal parasites in patients with diarrhea and human immunodeficiency virus infection in Zimbabwe. AIDS. 1999 May 7;13(7):819-21

 

Gumbo T, Hobbs RE, Carlyn C, Hall G, Isada CM. Microsporidia infection in transplant patients. Transplantation. 1999 Feb 15;67(3):482-4.

 

Carville A, Mansfield K, Widmer G, Lackner A, Kotler D, Wiest P, Gumbo T, Sarbah S, Tzipori S. Development and application of genetic probes for detection of Enterocytozoon bieneusi in formalin-fixed stools and in intestinal biopsy specimens from infected patients. Clin Diagn Lab Immunol. 1997 Jul;4(4):405-8.] 

 

9.       Pediatric Cryptococcus neoformans meningoencephalitis in AIDS (2002)

Key papers:

 

[Gumbo T, Kadzirange G, Mielke J, Gangaidzo IT, Hakim JG. Cryptococcus neoformans meningoencephalitis in African children with acquired immunodeficiency syndrome. Pediatr Infect Dis J. 2002 Jan;21(1):54-6.]

 

 

Current Grants

  

1.       Title: Pharmacometric optimization of second line drugs for MDR tuberculosis treatment

Project Number: 1R01AI116155                              (02/15/2015- 01/31/2020)

Source: National Institute of Allergy and Infectious Diseases/National Institutes Health

Role: Principal Investigator.

PI: Gumbo, Tawanda Gumbo, MD, & Helen McIlleron, MB,ChB, PhD

 

2.       Title: Hollow Fiber Sub-Award, Critical Path to TB Drug Regimens.

Project Number: OPP1031105                                 (01/01/2014-12/31/2015)

Source: Critical Path for TB Drug Regimens

Role: Principal Investigator

PI: Tawanda Gumbo, MD

 

3.       Title: Short course therapy for MDR-TB based on PK/PD answers for biological variability

Project Number: 1 R56 AI111985-01                       (08/01/2014-07/31/2015)

Source: National Institute of Allergy and Infectious Diseases/National Institutes Health

Role: Principal Investigator

PI: Tawanda Gumbo, MD

 

4.       Title: A human lung-orientated approach to correlates of risk in tuberculosis - The TB-HART study [Human lung-orientated Approach for correlates of Risk in TB].

Project Number: MRC-RFA-SHIP 02-2014                         (07/01/2014-06/31/2017)

Source: Medical Research Council of South Africa

Role: Co-investigator

PI: Keertan Dheda, MBBCh, PhD

 

 

 



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