Research Scientist IV
Division of Infectious Diseases
Wadsworth Center, New York State Department of Health
Lyme disease is the most prevalent vector-borne diseases in Northern hemisphere, including Northeastern and Midwest United States. This disease is caused by multiple species and strains of bacteria, Borrelia burgdorferi sensu lato. The bacteria are transmitted by ticks and spread from tick bite sites to different tissues via blood. In nature, the bacteria can be carried by reservoir animals (mainly birds and small rodents) without causing any symptoms. In humans, the infection of these bacteria often results in severe manifestations, including arthritis, carditis and several neurological symptoms. In addition to Lyme disease bacteria, ticks also transmit other pathogens, and such tickborne co-infections are commonly found in humans. However, no effective preventions for Lyme disease and other tickborne co-infection are currently available.
We are interested in defining the mechanisms of transmission and manifestations caused by Lyme disease bacteria and other tickborne pathogens, which can facilitate the development of prevention against spreading of these diseases.
- Investigate the mechanisms of host preferences to maintain and spread Lyme disease bacteria. The efficiency to be maintained in reservoir animals vary among different species or strains of Lyme disease bacteria, but the mechanisms that lead to such differences are unknown. In this study, we introduced different bacteria species/strains into reservoir hosts (white footed mice and American robins) or the avian and mammalian model animals (house mice and quail). We have shown that the host-to-host different ability to carry Lyme disease bacteria is determined by the variation of host immune responses (specifically, complement, antibody, and inflammatory responses) and/or polymorphisms of pathogen proteins that confer cell attachment and immune evasions. We also further defined several bacterial proteins as the determinants to contribute to transmission and long-term infection and identify the convergent evolution as the mechanism arisen through such host preferences to maintain and spread Lyme disease bacteria. Defining such mechanisms would impact the development of preventive strategies, allowing us by tweaking those bacterial determinants in the vaccines or prophylaxis to trigger similar immune responses in the incompetent hosts that would not allow bacterial survival. In this project, we are collaborating with Drs. Maria Diuk-Wasser in Columbia University and Sergios Kolokotronis in SUNY downstate Medical Center for the infection of white footed mice and phylogenic analysis.
- Develop the effective Lyme disease preventions and identify their protective mechanisms. Using the mechanisms elucidated above, we revised the sequences of a previously shown ineffective vaccine antigen, CspZ, to improve the protective antibody responses. We have shown that our patented invention for this revised new vaccine (CspZ-YA) can effectively prevent mice from the infection caused by multiple strains/species of Lyme disease bacteria. Additionally, we also examined the potential of two agents (FH-Fc and non-anticoagulant heparin) invented by our collaborators as pre-exposure prophylaxis and showed eradications of Lyme disease bacteria by those agents in vitro and/or in vivo. We further identified the modulation of antibody responses, complement-mediated killing, and adhesion blocking by these agents as their protective mechanisms against Lyme disease bacteria (see the above Figure, left panel). Examining the efficacy and identifying the protective mechanisms would impact the generation of prevention strategies to eventually reduce the burdens of human Lyme disease. In this project, we are collaborating with Drs. Maria-Elena Bottazzi in Baylor College of Medicine, Robert Linhardt in Rensselaer Polytechnic Institute, and Planet Biotech, Inc. to test the efficacy and define the protective mechanisms of those vaccines and prophylaxis.
- Define the role of tickborne co-infections in enhancing the Lyme disease severity. Antibiotic therapy is often effective for Lyme disease and tickborne coinfections, but some patients experience long-lasting complications for unknown causes. The ticks that carry Lyme disease bacteria can also transmit other pathogens, including species of Ehrlichia, Babesia, Anaplasma. Patients with Lyme disease and other tickborne diseases often exhibit more severe Lyme disease-associated manifestations, but the mechanism that drives such enhanced severity is unknown. Using Lyme disease bacteria and Ehrlichia (and Babesia) as a model of tickborne coinfections, we have shown the role of less robust early innate myeloid cells to enhance the burdens of Lyme disease bacteria during coinfections with Ehrlichia, which is linked to the increasing severity and pathogen dissemination in joints at late stages of coinfections (see the above Figure, right panel). These results would impact the development of new therapeutics for tickborne coinfection. The key players of immune responses identified in this work to promote bacterial dissemination and Lyme disease-associated manifestations during co-infection could be modulated as a new therapeutic strategy. In this project, we are applying our mouse model of tickborne coinfection to examine such a concept in my laboratory, with the collaboration from Dr. Kate MacNamara in Albany Medical College to provide the characterization of the immunological mechanisms.
- Drug discovery and therapeutics
- Infection and immunity
The courses we have been providing
- BMS 692 Microbial Pathogenesis (Offered by the UAlbany School of Public Health) Lecture: Adherance and Host Tropisms, Lecture: Borrelia burgdorferi and other spirochetes - This course provides students with a background in the mechanisms of microbial pathogenesis and an appreciation of the continuing and serious impact of infectious disease on modern life. Students will learn basic principles of host-parasite interactions and how human behavior has influenced both the resurgence of old diseases and the emergence of new ones. Intervention strategies, including vaccination and drug therapy, will be discussed, and reasons for the successes and failures of these approaches will be considered for individual cases. Finally, paradigms of host-parasite interactions will be illustrated by studying, at the molecular and cellular levels, specific infectious diseases and the agents that cause them.
- BMS 506 Introduction to Immunology (Offered by the UAlbany School of Public Health) Lecture: Complement system - This introductory immunology course BMS 506 is designed for non-majors, or individuals beginning their study in the field of Immunology. All the lectures are designed for students to gain fundamental knowledge about the immune system, immunological processes and what occurs during immunological disorders. This course will also allow the student to obtain a strong foundation in immunology in order to be able to take advanced courses in immunology or do immunology based lab work.
- CIMD 602 Advanced Immunology (Offered by Albany Medical College) Lecture: Complement system - This is an upper-level literature-driven course with an emphasis on novel findings and emerging concepts in Immunology. It is designed for students who already took the beginning Immunology Course. The goal is to fill in gaps on topics not covered in the introductory course, and to expand on their knowledge of techniques and approaches (as well as the challenges) in addressing important questions in the field.
- BMS 552 Medical Entomology (Offered by the UAlbany School of Public Health) Lecture: The interactions between ticks and tickborne pathogens - This course will focus on the ecology and biology of insect and tick vectors of pathogens causing both tropical and temperate diseases such as malaria, Lyme disease, African sleeping sickness, Chagas' disease, dengue, chikungunya, West Nile and Zika.
We are looking for motivated PhD/Master, undergraduate students with enthusiasms and curiosity on science. If you are interested in any topics that we are currently studying, and you are organized, willing to contribute time to the research, able to tolerate the failure, and are capable of handling your stress, you are who we are looking for!
The lab members and the research projects in our laboratory are supported by National Institutive of Health, National Science Foundation, Department of Defense, and New York State Department of Health.
Feel free to contact us through [email protected] for more information on our laboratory.