Shaden Kamhawi, Ph.D.

The research program is focused on basic and translational aspects of insect-borne diseases, with a focus on leishmaniasis. Leishmaniasis is an infectious disease endemic in southern states, including Texas and Oklahoma, and is also prevalent in foxhound dogs throughout the United States. Importantly, leishmaniasis has been one of the major afflictions in U.S. soldiers and military working dogs (MWD) deployed to endemic regions.

Basic and preclinical research: The team is developing recombinant antigens to improve disease diagnosis and to assess the risk of exposure to insects and ticks. We are also investigating the human immune response to pathogens transmitted by insects and ticks that transmit leishmaniasis and Lyme disease, respectively. In a study of leishmaniasis, we demonstrated the critical contribution of insect vectors in the initiation and establishment of disease. We demonstrated that insect-derived factors lead to acute inflammation key to pathogen establishment and dissemination in the host. The group also showed that bleeding at the site of insect or tick bites that is prolonged due to the anti-hemostatic effects of saliva triggers the cell stress response and heme oxygenase-1 induction, which dampens inflammation and promotes pathogen survival. These bite-specific immune events shape the early response to transmitted pathogens and have lasting effects on disease outcome. The group continues to investigate the host immune response to insect bites, which is essential to the development of therapeutics and novel interventions.

Clinical research: The team is currently developing a Controlled Human Infection Model (CHIM) of cutaneous leishmaniasis at the NIH clinical center in collaboration with Dr. Matthew Memoli (Director, LID Clinical Studies Unit) and Josh Lacsina (Assistant Clinical Investigator, Multiscale Systems Biology Section). The CHIM will be used to investigate the efficacy of promising vaccines and therapeutics against leishmaniasis using infected sand flies as a challenge. We are currently collaborating to validate a leading live attenuated vaccine developed by Hira Nakhasi (U.S. Food and Drug Administration), Abhay Satoskar (Ohio State University), and Greg Matlashewski (McGill University) that has shown high efficacy in preclinical studies.

Translational research: Dr. Kamhawi is collaborating with Dr. Naomi Aronson at the Uniformed Services University of the Health Sciences (USUHS) to investigate exposure to Leishmania parasites and sand fly vector bites in U.S. soldiers deployed to endemic areas of the Middle East. Leishmaniasis is also a chronic and fatal disease for dogs and has affected MWD deployed to endemic areas. Due to the chronicity of the disease, leishmaniasis-infected dogs can return to the U.S. while infected and can potentially transmit the parasites to local species of sand flies such as Lutzomyia (Lu.) shanonni and Lu. diabolica. Dr. Kamhawi is continuing to collaborate with Drs. Aronson and Davies at USUHS who are interested in investigating the prevalence of arthropod-borne pathogens in military facilities within the U.S. Additionally, in collaboration with Dr. Christy Peterson at Ohio State University (OSU), Dr. Kamhawi is investigating the transmissibility of Leishmania infections prevalent in foxhound dogs throughout the U.S. These studies are critical to assess the risk of emergence of leishmaniasis in the U.S. Dr. Kamhawi is also looking at drivers of transmission in cutaneous and visceral leishmaniasis foci and using diagnostic antigens her group developed as a surveillance tool to monitor direct human-vector contact in endemic populations. She is also working with Dr. Jesus Valenzuela to screen sera from inhabitants of Lyme disease and Rocky Mountain Spotted Fever endemic regions in the U.S. to develop diagnostic tools that assess exposure to ticks and tick-borne pathogens.

A tridimensional view of a macrophage (IBA-1, yellow; DAPI, blue) from mouse skin expressing heme oxygenase-1 (HO-1, red) after ingesting a red blood cell (TER-119, white) 18 hours after sand fly bites.

Credit: NIAID