Areas of Research: Cerebral malaria: mechanisms of longterm cognitive dysfunction; regulation and activation of vasoactive mediators; modulators of blood-brain barrier impairment, and of neuronal and glial cell dysfunction.
Dr. Mahalia Desruisseaux has been working on a murine model of cerebral malaria since her Infectious Diseases fellowship at the Albert Einstein College of Medicine. Her laboratory has been interested in investigating aberrant regulation of vascular tone, inflammation, blood-brain barrier disturbances, and eventually neuronal and glial cell degeneration in the brains of mice with experimental cerebral malaria, and exploring the potential effects on neurological outcomes. Her focus is on alterations in the synthesis and activation of vasoactive compounds during parasitic disease, and exploring the effects on cerebral perfusion, inflammation and blood-brain barrier disruption, and on aberrant regulation of cell survival pathways which may lead to neuronal damage and to long-term neurological deficits. Her studies have led to some interesting discoveries, for example, her laboratory group was the first to describe an increase in all the components of the endothelin pathway in the mouse model, which was associated with a decrease in cerebral blood flow. They also demonstrated that tau protein, a protein important in the formation of neurofibrillary tangles in neurodegenerative diseases, is abnormally regulated in an experimental model of cerebral malaria.
The lab has refined and optimized imaging modalities to directly visualize the brain microvasculature via intravital microscopy of live animals, a method that allows up a direct longitudinal view of the brain during the course of malarial disease, including examination of any inflammatory process, and blood-brain barrier perturbances in real-time fashion. In addition, in collaboration with Dr. David Spray's laboratory (in the Department of Neuroscience), they have optimized live mouse brain imaging of the blood-brain barrier and inflammation using near-infrared imaging in an In Vivo Imaging System (IVIS). The Desruisseaux lab utilizes a number of additional assays to examine outcomes in infected mice, including cognitive tests, and microPET imaging. As part of the Einstein Global Health Center's capacity building efforts, Dr. Desruisseaux has also developed collaborations with scientists at the University of Malawi College of Medicine in Blantyre Malawi. Their investigations into the mechanisms leading to persistent cognitive deficits associated with disease should define targets for therapy and establish new hypotheses for future research on cerebral malaria.
- Machado FS*, Desruisseaux MS*, Nagajyothi, Kennan RP, Hetherington HP, Wittner M, Weiss LM, Lee SC, Scherer PE, Tsuji M, Tanowitz HB. Endothelin in a murine model of cerebral malaria. Experimental Biology and Medicine. 2006; 231:1176-1181. *co-first authors
- Ashton AW, Mukherjee S, Nagajyothi F, Huang H, Braunstein VL, Desruisseaux MS, Factor SM, Lopez L, Berman JW, Wittner M, Scherer PE, Capra V, Coffman TM, Serhan CN, Gotlinger K, Wu KK, Weiss LM, Tanowitz HB. Thromboxane A2 is a key regulator of pathogenesis during Trypanosoma cruzi infection. Journal of Experimental Medicine. 2007; 204: 929-940.
- Desruisseaux MS, Gulinello M, Smith DN, Lee SC, Tsuji M, Weiss LM, Spray DC, Tanowitz HB. Cognitive dysfunction in mice infected with Plasmodium berghei ANKA. Journal of Infectious Diseases. 2008; 197:1621-1627.
- Desruisseaux MS, Iacobas DA, Iacobas S, Mukherjee S, Weiss LM, Tanowitz HB, Spray DC. Alterations in the brain transcriptome in Plasmodium berghei ANKA infected mice. Journal of Neuroparasitology. Vol. 1 (2010), Article ID N100803.
- Desruisseaux MS, Machado FS, Weiss LM, Tanowitz HB, Golightly LM. Cerebral malaria: a vasculopathy. American Journal of Pathology. 2010; 176:1075-1078.
- Dai M, Reznik SE, Spray DC, Weiss LM, Tanowitz HB, Gulinello M, Desruisseaux MS. Persistent cognitive and motor deficits after successful antimalarial treatment in murine cerebral malaria. Microbes and Infection 2010; 12:1198-1207.
- Dai M, Freeman B, Bruno FP, Shikani HJ, Tanowitz HB, Weiss LM, Reznik SE, Stephani RA, Desruisseaux MS. The novel ETA receptor antagonist HJP-272 prevents cerebral microvascular hemorrhage in cerebral malaria and synergistically improves survival in combination with an artemisinin derivative. Life Sci. 2012; 91:687-92.
- Dai M, Freeman B, Shikani HJ, Bruno FP, Collado JE, Macias R, Reznik SE, Davies P, Spray DC, Tanowitz HB, Weiss LM, Desruisseaux MS. Altered regulation of Akt Signaling with Murine Cerebral Malaria, Effects on Long-term Neuro-cognitive Function, Restoration with Lithium Treatment. PLoS One. 2012; 7:e44117.
- Shikani HJ, Freeman B, Lisanti MP, Weiss LM, Tanowitz HB, Desruisseaux MS. Cerebral malaria: we have come a long way. American Journal of Pathology. 2012; 181:1484-92.
- Freeman BD, Martins YC, Akide-Ndunge OB, Bruno FP, Wang H, Tanowitz HB, Spray DC, Desruisseaux MS. Endothelin-1 mediates brain microvascular dysfunction leading to long-term cognitive impairment in a model of experimental cerebral malaria. PLOS Pathogens. 2016;12(3):e1005477.
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