Leishmaniasis Pathogenesis/Diagnostics/Drug Discovery
Leishmaniasis is a neglected vector-borne disease caused by protozoan parasites, and each Leishmania species is uniquely associated with distinct clinical manifestations. We take an integrative systems-level approach to identify novel regulatory circuits that direct immune responses in the host cells of Leishmania parasites, dendritic cells and macrophages.
Atypical clinical manifestations of leishmaniasis can present in HIV+ individuals. Coupled with additional opportunistic infections that occur in HIV+ patients and a lack of diagnostic facilities in low-income countries, diagnosing leishmaniasis can be a challenge. Current rapid diagnostic assays are not accurate in some geographical locations and other diagnostic methods are invasive. Therefore, an alternative, non-invasive, diagnostic approach such as an antigen test is needed. Disease specific exosomes are being developed as diagnostic markers for cancer and infectious diseases. Exosomes are small membrane vesicles released by cells which have been shown to contain microbial components when released from infected cells. The purification of exosomes prior to microbial protein detection is thought to concentrate these components for detection. Here, are assessing the proteome of exosomes isolated from the plasma of infected patients to identify potential diagnostic proteins.
Our research team has built a robust drug discovery platform, utilizing fluorometric high-throughput screening (HTS) with small molecule libraries followed by combinatorial chemistry. As traditional drug discovery approaches have not been robust for discovering anti-Leishmania compounds, we developed a simple fluorometric method for primary drug screening using Leishmania parasites expressing a red fluorescence protein. A HTS screening of diverse small molecules against the intracellular stage of the parasite both in vitro and in vivo has identified two novel scaffolds with anti-leishmanial activity.
Leishmania parasites are transmitted by the bite of a phlebotomine sand fly. We evaluate the feasibility of using sand fly saliva as a vaccine component to combat leishmaniasis by assessing human immune responses to sand fly saliva and genetic variability of sand fly populations in the Middle East.
At the EIGH, our researchers use biochemistry - or the study of chemical substances and their vital role within living organisms - to combat various global health challenges, such as antibiotic resistance and counterfeit drugs.
At the EIGH, our researchers work to combat a number of various illnesses, including infectious diseases caused by organisms like bacteria, viruses, fungi, and parasites. These diseases can also be spread from one person to another and may be transmitted from animals to humans.
Molecular Biology and Microbiology
Researchers at the EIGH use microbiology, which encompasses the study of an entire microorganism, and molecular biology, or the interactivity between molecules within a cell of an organism, to better understand disease and improve global health.
Vector-borne disease research is a historic strength of the EIGH. Our researchers study multiple parts of the vector-borne disease lifecycle, such as how the parasites, viruses, and bacteria cause these kinds of diseases, how the vectors spread these diseases, and how to improve prevention methods in tropical and subtropical areas, which have the highest burden of vector-borne illnesses.
- Al-Quds University, Palestine
- Jordan University of Science and Technology, Jordan
- NAMRU-3, United States Navy, Egypt
- University of Gondar College of Medicine & Health Sciences, Ethiopia
UNIVERSITY OF NOTRE DAME PARTNERSHIPS
- Genomics & Bioinformatics Core Facility
- Mass Spectrometry & Proteomics Facility
- Warren Family Research Center for Drug Discovery and Development
Polando, R., B. Jones, C.Ricardo, J.P. Whitcomb, W. Ballhorn, and M.A. McDowell. Role of mannose receptor in phagosome maturation during Leishmania infection.
Favila, M.A., N.S. Geraci, A. Jayakumar, S.A. Hickerson, S.J. Turco, S.M. Beverley, and M.A. McDowell, Leishmania major Friedlin V1 LPG and PG deficient mutants influence the human dendritic cell interleukin-12 immune response.
Geraci, N.S. , J.C. Tan, and M.A. McDowell. Characterization of microRNA Expression Profiles in Leishmania Infected Human Phagocytes.
Mukbel, R.M., R. H. Khasharmeh, N.S. Hijjawi, M.S. Khlaifeh, M.M. Hatmal, and M.A. McDowell. Human immune response to wild Phlebotomus papatasi salivary proteins.
Ramalho-Ortigao, M., I.V. Coutinho-Abreu, I.V. V.Q, Balbino, C.A.S. Figueiredo, R. Mukbel, H. Dayem, H.A. Hanafi, S.S. El-Hossary, E.E.Y. Fawaz, M. Abo-Shehada, D.L. Hoel, G. Stayback, M. Wadsworth, D.A., Shoue, J.A. Abrudan, N. F. Lobo, A.R. Mahon, S.J. Emrich, S. Kamhawi, F.H. Collins, and M.A. McDowell. Phlebotomus papatasi SP15: mRNA expression variability and amino acid sequence polymorphisms of field populations with potential impact for vaccine development.
Okenfels, B., E. Michael and M.A. McDowell. Meta-analysis of the effects of insect vector saliva on the host immune response and progression of disease.
Geraci, N.S., R. M. Mukbel, M.T. Kemp, M.N. Wadsworth, G.M. Stayback, M.M. Champion, M.A. Bernar4, M. Abo-Shehada, I.V., Coutinho-Abreu, M. Ramalho-Ortigao, H.A. Hanafi, E.Y. Fawaz, S.S. El-Hossary, D.F. Hoel and M.A. McDowell. Profiling of human acquired immunity against the salivary Proteins of Phlebotomus papatasi reveals clusters of differential immunoreactivity.
Durst, K. (2018). The Utility of Exosomes as Diagnostic Biomarkers for Visceral Leishmaniasis (2018).
Anderson, J. (2017). Knowledge, Attitude, and Practice of Leishmaniasis in Districts of Amhara Region, Ethiopia.
Jacobson, X. (2017). The Utility of Exosomes as Diagnostic Biomarkers for Visceral Leishmaniasis (2017).