Dennis E. Kyle, Ph.D.
USF Health - College of Public Health

 

Professor Dennis E. Kyle

Department of  Global Health

College of Public Health

3720 Spectrum Blvd, Suite 304

Tampa, FL 33612

Office: (813) 974-1273

Lab: (813) 974-7191 or 4-4578

dkyle@health.usf.edu   

Kyle Biosketch       

PubMed Articles

    

 

Kyle Lab at USF Interdisciplinary Research Building

Affiliations:

 Global Health Infectious Disease Research (GHIDR) Program

 Center for Biological Defense (CBD)

 Center for Molecular Diversity in Drug Design, Discovery, and Delivery (CMD5)

 Center of Excellence for Biomolecular Identification and Targeted Therapeutics (BITT)

 Consortium for Parasitic Drug Development (CPDD)                           

 International Cooperative Biodiversity Group - Panama (ICBG)

 Signature Interdisciplinary Program for Allergy, Immunology, and Infectious Diseases 


P. falciparum in human erythrocytes
  • Chemotherapy and Drug Resistance Research: The research in the Kyle lab focuses on the discovery and development of new drugs to prevent or treat malaria and leishmaniasis, two of the most important parasitic diseases of man. Both of these diseases are major public health problems and cause significant mortality and morbidity in many tropical and temperate regions of the world. New drugs are urgently needed to combat malaria, primarily due to the emergence of drug resistance to one or more drugs - a phenomenon known as multidrug resistance. Elucidating mechanism(s) of resistance and discovering new drug treatment regimens, combinations, or strategies to overcome resistance is a second major research focus. The overarching objectives of our research is to develop new tools to prevent disease, to train a new generation of global health research scientists, to foster multidisciplinary research on tropical diseases, and to implement our findings to reduce the burden of disease in endemic countries.

  • Mechanism(s) of Antimalarial Drug Resistance: The development and spread of drug resistance in malaria parasites has become a major obstacle in the treatment and control of a disease that causes approximately 300 million infections and up to 3 million deaths per year. Artemisinin, and its derivatives, offer new hope in the effective treatment of malaria. This class of drugs rapidly clears clinical symptoms and parasites, including those that are multi-drug resistant. Unfortunately, when these drugs are used alone, > 40% of cases will produce recrudescent infections. Unlike recrudescence following treatment by other anti-malarial drugs, parasites appearing after artemisinin treatment remain susceptible to artemisinin. Our preliminary data suggests that P. falciparum parasites have a unique mechanism to survive artemisinin treatment: The drugs induce a dormant ring stage parasite in which growth is arrested for several days before the parasites recover and grow normally. This project, support by NIAID, aims to investigate the rate at which dormant parasites develop and recover following treatment with various artemisinin derivatives in vitro. Although conventional resistance to artemisinin drugs has not yet been observed in the field, experiences with all other antimalarial drugs indicate the  significant risk of parasites developing resistance to artemisinin drugs. We have developed artemisinin resistance in P. falciparum in our laboratory and will characterize the cellular and molecular mechanism(s) associated with resistance. These include transcriptional, translational/post-translational changes and mutations in potential drug transporters. This component of the project will elucidate possible mechanisms by which parasites develop resistance to this class of drug and the role of artemisinin-induced dormancy in the process. The results of this project will provide valuable information regarding the mechanisms of treatment failure for artemisinin drugs. The results will aid the formulation of optimal ACT regimens, improved treatment outcomes for malaria patients and defined strategies of preventing the development of resistance. This project is a collaboration between the Kyle Lab and Qin Cheng's Lab at the Australian Army Malaria Institute.

    Amastigotes of L. donovani in human spleen
  • Drug Discovery for Leishmaniasis: Leishmaniasis is a parasitic disease of humans and animals caused by Leishmania spp.  The World Health Organization estimates leishmaniasis is endemic in 88 countries with 12 million people currently infected and approximately 2 million new cases each year. The disease has three major clinical manifestations: cutaneous, visceral, and mucocutaneous disease. There is no vaccine for preventing the disease and the treatment drugs have drawbacks such as serious side effects, lengthy treatment, and drug resistance, especially to first line pentavalent antimonials. New, less expensive, orally administered drugs are particularly important for the economically disadvantaged areas where the disease is endemic. The Kyle lab is part of the Consortium for Parasitic Drug Development (CPDD) working to discover and develop new treatments for leishmaniasis and human African trypanosomiasis. Current efforts focus on several novel series of dicationic compounds related to pentamidine, yet additional hits and lead compounds are being evaluated. The Kyle lab contributes expertise in preclinical drug development plus in vitro and in vivo evaluation of new drug candidates for CPDD.
  • Natural Product Drug Discovery: The history of antimalarial drug discovery and development provides ample evidence to support the screening of natural products to discover new drugs to treat malaria. The two most important antimalarial drugs, quinine and artemisinin, both come from natural products. Similarly, natural products have accounted for approximately 60% of the new anticancer and anti-infective drugs, either as new agents or compounds based upon a pharmacophore from a natural product. The Kyle laboratory is actively engaged in natural product drug discovery with colleagues from USF Department of Chemistry (Dr. Bill Baker), USF Center for Biological Defense (Dr. Alberto van Olphen), Magellan BioScience Group, Inc. In addition Prof. Kyle serves as an Associate Program leader for the International Cooperative Biodiversity Group - Panama, which is an active consortium devoted to natural product drug discovery for multiple diseases.

  • Drug Discovery for Potentially Pathogenic Free-Living Amoebae:  Free-living amoebae of the genera Naegleria and Acanthamoeba are prevalent in soil and freshwater and some species can cause life-threatening disease in humans. Naegleria fowleri is the causative agent of primary amoebic meningoencephalitis (PAM). The primary victims of this usually fatal disease are most often young and healthy with a history of exposure in warm freshwater lakes. There were six reported deaths from PAM in the US in 2007, with three of the cases ocurring in Florida. Acanthamoeba sp. may cause granulomatous amoebic meningoencephalitis (GAE) in immunocompromised individuals or keratitis. There are few drugs to treat these diseases, especially the neurologocal manifestations. In collaboration with Dr. David Boykin (Georgia State University) we currently are evaluating a series of diamidine derivatives a potential drugs for treating PAM and GAE.

    Location: The Kyle labs are located in Suite 419 & 425 of the new Interdisciplinary Research Building (IDRB) at the USF Research Park. Current members of the lab are listed below:

     

        Anupam Pradhan, PhD (Post-doc)

        Alexis Lacrue, PhD (Post-doc)

        Fabian Saenz, PhD (Post-doc)

        Anuradha Srivastava, PhD (Post-doc)

        Susan Lukas, MPH (PhD student)

        Matt Tucker, MSPH, MS (PhD student)

        Tina Mutka, MPH (research assistant)

        Michelle Bailey (MPH student)

        Katherine Jane Barkan (MSPH student)

        Jessica Schilke (MPH student)

        Brian Vesley (MPH student)

        Azliyati Azizan, PhD (Asst. Prof.)

        Preeyaporn Monatrakul, (PhD student from Mahidol University, Bangkok, Thailand)

     



  • Prospective Students: Currently enrolled USF students interested in conducting their MPH special project or MSPH thesis in the Kyle lab should submit a statement of  interest 2-3 months prior to the beginning of the proposed project period.

  • Teaching: PHC 6513 - Public Health Parasitology

                        PHC 7931 - Current Topics in Global Health Infectious Diseases