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Mahalia S. Desruisseaux, MD

Associate Professor of Medicine (Infectious Diseases); Affiliated Faculty, Yale Institute for Global Health

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Mahalia S. Desruisseaux, MD
Yale Medicine

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Research Summary

The focus of the Desruisseaux laboratory is on the brain microvascular and neural cell responses to parasitic infections that lead to debilitating neurological sequelae and mortality, and on the mechanisms that underlie these responses.

Extensive Research Description

The Desruisseaux laboratory works on cerebral malaria, a disease in which > 25% of survivors suffer from persistent neurological and cognitive deficits, despite successful anti-parasitic treatment. The goal of the laboratory is to identify the factors that cause these adverse long-term neurological sequelae.

The Desruisseaux lab has been particularly interested in the aberrant regulation of cerebral vascular tone, inflammation, blood-brain barrier disturbances, and eventually neuronal and glial degeneration after plasmodial infection, using a mouse model of experimental cerebral malaria. Our focus is on alterations in the synthesis and activation of vasomodulatory compounds during parasitic disease, and the effects of these alterations on cerebral perfusion, inflammation and blood-brain barrier disruption, and ultimately on gliopathy, neuronal damage and long-term neurological deficits. We identified endothelin-1, a potent vasoactive peptide with mitogenic and pro-inflammatory properties, as a key contributor to endothelial remodeling, neuroinflammation, long-term neurological damage and mortality during cerebral malaria. We also demonstrated that tau protein, a protein important in the formation of neurofibrillary tangles in neurodegenerative diseases, is abnormally regulated in our experimental model, demonstrating that long term sequelae are the result of potentially reversible vascular, biochemical and physiological changes in brains of infected mice.

In collaboration with investigators at the University of Malawi College of Medicine in Blantyre Malawi and at Indiana University, our laboratory will study the mechanisms of the disease process in pediatric patients from malaria endemic regions to test the translatability of our findings in the experimental model and to potentially derive novel therapeutic targets.


Coauthors

Research Interests

Blood-Brain Barrier; Neuroglia; Neurons; Chagas Disease; Endothelins; Malaria, Cerebral; Neurocognitive Disorders; Central Nervous System Parasitic Infections; Endothelial Cells

Public Health Interests

Global Health; Infectious Diseases; Malaria; Neglected Tropical Diseases

Selected Publications

  • Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized PatientsOrtigoza MB, Yoon H, Goldfeld KS, Troxel AB, Daily JP, Wu Y, Li Y, Wu D, Cobb GF, Baptiste G, O’Keeffe M, Corpuz MO, Ostrosky-Zeichner L, Amin A, Zacharioudakis IM, Jayaweera DT, Wu Y, Philley JV, Devine MS, Desruisseaux MS, Santin AD, Anjan S, Mathew R, Patel B, Nigo M, Upadhyay R, Kupferman T, Dentino AN, Nanchal R, Merlo CA, Hager DN, Chandran K, Lai JR, Rivera J, Bikash CR, Lasso G, Hilbert TP, Paroder M, Asencio AA, Liu M, Petkova E, Bragat A, Shaker R, McPherson DD, Sacco RL, Keller MJ, Grudzen CR, Hochman JS, Pirofski LA, Rahman F, Ajayi A, Rodriguez S, Ledesma A, Keeling D, Rappoport N, Ebel S, Kim J, Chang M, Chan K, Patel P, Martocci A, Dave S, Darwish Y, Taveras M, Shoyelu V, Xin P, Iturrate E, Moldolsky L, Raimondo B, Mendez S, Hughes P, Sterling S, Lord A, Yaghi S, Veloso K, Sheikh M, Visconti-Ferrara E, Fleming A, Youn H, Jane Fran B, Medina R, McKell R, Khan S, Hamilton T, Sanchez C, Patel N, Cleare L, Vergnolle O, Nakouzi A, Quevedo G, Bortz R, Wirchnianski A, Florez C, Babb R, Ayala J, Tsagaris K, James A, Eke I, Obeidallah A, Sandu O, Sohval S, Serrano-Rahman L, Uehlinger J, Bartash R, Al-Abduladheem A, Gendlina I, Sheridan C, Bortnick A, Eichler J, Kaufman R, Yukelis S, Pennock M, Goggin M, Shen C, Annam J, Khokhar A, Barboto D, Lally B, Lee A, Lee M, Yang X, Allen S, Malaviya A, Moussa O, Park R, Sample R, Bae A, Benoni G, Boerger L, Baker L, Luther M, Ameti L, Briggs N, Golden M, Gormally M, Huang G, Johnson R, Morrison A, Montagna-Hill M, Rivera B, Cortezzo G, Debski K, Nicoletti, DeBenedictis K, Davis R, Marshall C, Duque Cuartas M, Beauchamps L, Bertran-Lopez J, Gonzales Zamora J, Delgado-Lelievre M, Dominguez S, Lee C, Kusack H, Karakeshishyan V, Hajaz A, Deniz D, Garcia G, Dae K, Blenet P, Jaffe D, Olson L, Sabogal D, Blust O, Del Prete Perez V, Bornia C, Rodriguez-Perez V, Calderon V, Ramdev R, Jolly A, Guzman I, Guerra R, Brito S, Hobbs R, Denham R, Dick J, Hernandez M, Nielsen L, Anjum S, Mader S, Stutz T, Mammadova M, Nichols P, Khan T, Boktour M, Castaneda B, Benitez B, Hinojosa E, Guerra B, Ortiz A, Hebbeler-Clark R, McShane P, Hibbard R, Hawkins B, Dohanich E, Wadle C, Greenlee K, Brooks J, Herrick C, Gode A, Bergl P, Hu K, Patel J, Srinivasan S, Graf J, Klis C, Reimer K, Carpenter E, Naczek C, Petersen R, Dex R, Drossart J, Zelten J, Brummitt C, Liang M, Yanny L, Dennison G, Runningen P, Brzezinski B, Fiebig S, Naczek C, Kasdorf M, Parameswaran L, Corcoran A, Rohatgi A, Wronska M, Wu X, Srinivasan R, Deng F, Filardo T, Pendse J, Blaser S, Whyte O, Gallagher J, Thomas O, Ramos D, Sturm-Reganato C, Fong C, Daus I, Payoen A, Chiofolo J, Friedman M, Wu D, Jacobson J, Schneider J, Sarwar U, Wang H, Huebinger R, Dronavalli G, Bai Y, Grimes C, Eldin K, Umana V, Martin J, Heath T, Bello F, Ransford D, Laurent-Rolle M, Shenoi S, Akide-Ndunge O, Thapa B, Peterson J, Knauf K, Patel S, Cheney L, Tormey C, Hendrickson J. Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients JAMA Internal Medicine 2022, 182: 115-126. PMID: 34901997, PMCID: PMC8669605, DOI: 10.1001/jamainternmed.2021.6850.
  • 87. Infectious Disease Diversity, Equity, and Antiracism (ID2EA): A Dedicated Curriculum for Infectious Disease ProfessionalsGleeson S, Bathgate M, Frederick J, Desruisseaux M, Meyer J, Virata M, Zapata H, Shenoi S, Radin J, Golden M, Trubin P, Shaw A, Friedland G, Aoun-Barakat L. 87. Infectious Disease Diversity, Equity, and Antiracism (ID2EA): A Dedicated Curriculum for Infectious Disease Professionals Open Forum Infectious Diseases 2021, 8: s55-s55. PMCID: PMC8644171, DOI: 10.1093/ofid/ofab466.087.
  • Early but not late convalescent plasma is associated with better survival in moderate-to-severe COVID-19Briggs N, Gormally MV, Li F, Browning SL, Treggiari MM, Morrison A, Laurent-Rolle M, Deng Y, Hendrickson JE, Tormey CA, Desruisseaux MS. Early but not late convalescent plasma is associated with better survival in moderate-to-severe COVID-19 PLOS ONE 2021, 16: e0254453. PMID: 34320004, PMCID: PMC8318280, DOI: 10.1371/journal.pone.0254453.
  • Use of Convalescent Plasma Therapy in Severe Coronavirus Disease 2019: The Yale-New Haven Health System ExperienceBrowning S, Gormally M, Briggs N, Li M, Zakko A, Laurent-Rolle M, Ladines-Lim J, Morrison A, Kandel P, Khan M, McLeod G, Buller G, Owusu K, Treggiari M, Hendrickson J, Tormey C, Desruisseaux M. Use of Convalescent Plasma Therapy in Severe Coronavirus Disease 2019: The Yale-New Haven Health System Experience Blood 2020, 136: 39-40. PMCID: PMC8330251, DOI: 10.1182/blood-2020-137352.
  • Inclusion, Diversity, Access, and Equity (IDA&E) Roadmap: Infectious Diseases Society of America’s Commitment to the FutureDesruisseaux MS, Tan TQ. Inclusion, Diversity, Access, and Equity (IDA&E) Roadmap: Infectious Diseases Society of America’s Commitment to the Future The Journal Of Infectious Diseases 2020, 222: s523-s527. PMID: 32926738, DOI: 10.1093/infdis/jiaa153.
  • Captain Herbert B. Tanowitz, M.D., F.I.D.S.A., F.A.C.P., F.R.S.T.M.H., 1941–2018Desruisseaux M, Engman D. Captain Herbert B. Tanowitz, M.D., F.I.D.S.A., F.A.C.P., F.R.S.T.M.H., 1941–2018 American Journal Of Pathology 2019, 189: 2-3. DOI: 10.1016/j.ajpath.2018.10.003.
  • Endothelins in inflammatory neurological diseasesD'Orléans-Juste P, Akide Ndunge O, Desbiens L, Tanowitz HB, Desruisseaux MS. Endothelins in inflammatory neurological diseases Pharmacology & Therapeutics 2018, 194: 145-160. PMID: 30291906, PMCID: PMC6348026, DOI: 10.1016/j.pharmthera.2018.10.001.
  • Trypanosoma cruzi Produces the Specialized Proresolving Mediators Resolvin D1, Resolvin D5, and Resolvin E2Colas RA, Ashton AW, Mukherjee S, Dalli J, Akide-Ndunge OB, Huang H, Desruisseaux MS, Guan F, Jelicks LA, dos Santos F, Nagajyothi J, Zingman MA, Reyes J, Weiss LM, Serhan CN, Tanowitz HB. Trypanosoma cruzi Produces the Specialized Proresolving Mediators Resolvin D1, Resolvin D5, and Resolvin E2 Infection And Immunity 2018, 86: e00688-17. PMID: 29358332, PMCID: PMC5865043, DOI: 10.1128/iai.00688-17.
  • Endothelin-1 Treatment Induces an Experimental Cerebral Malaria–Like Syndrome in C57BL/6 Mice Infected with Plasmodium berghei NK65Martins YC, Freeman BD, Ndunge O, Weiss LM, Tanowitz HB, Desruisseaux MS. Endothelin-1 Treatment Induces an Experimental Cerebral Malaria–Like Syndrome in C57BL/6 Mice Infected with Plasmodium berghei NK65 American Journal Of Pathology 2016, 186: 2957-2969. PMID: 27640146, PMCID: PMC5222963, DOI: 10.1016/j.ajpath.2016.07.020.
  • Endothelin-1 Mediates Brain Microvascular Dysfunction Leading to Long-Term Cognitive Impairment in a Model of Experimental Cerebral MalariaFreeman 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: e1005477. PMID: 27031954, PMCID: PMC4816336, DOI: 10.1371/journal.ppat.1005477.
  • Chapter 14 Trypanosoma cruzi and Chagas Disease: Innate Immunity, ROS, and Cardiovascular SystemTanowitz H, Wen J, Machado F, Desruisseaux M, Robello C, Garg N. Chapter 14 Trypanosoma cruzi and Chagas Disease: Innate Immunity, ROS, and Cardiovascular System 2016, 183-193. DOI: 10.1016/b978-0-12-801078-5.00014-5.
  • The Brain Microvasculature in Cerebral MalariaDorovini-Zis K, Stins M, Desruisseaux M, Martins Y, van der Heyde H. The Brain Microvasculature in Cerebral Malaria 2015, 68-117. DOI: 10.1201/b19299-5.
  • 228Building Bridges: Improving Antibiotic Prescribing in the Emergency DepartmentMadaline T, Feldmesser M, Chung P, Daily J, Desruisseaux M, Hochman S, Keller M, Leviton I, Murphy K, Sharma A, Pearlman S, Katz N, White D, Pirofski L, Ostrowsky B. 228Building Bridges: Improving Antibiotic Prescribing in the Emergency Department Open Forum Infectious Diseases 2014, 1: s99-s99. DOI: 10.1093/ofid/ofu052.94.
  • Endothelin-1 and its role in the pathogenesis of infectious diseasesFreeman BD, Machado FS, Tanowitz HB, Desruisseaux MS. Endothelin-1 and its role in the pathogenesis of infectious diseases Life Sciences 2014, 118: 110-119. PMID: 24780317, PMCID: PMC4538933, DOI: 10.1016/j.lfs.2014.04.021.
  • Endothelin-1 treatment induces experimental cerebral malaria during Plasmodium berghei NK65 infectionMartins Y, Tanowitz H, Weiss L, Desruisseaux M. Endothelin-1 treatment induces experimental cerebral malaria during Plasmodium berghei NK65 infection Life Sciences 2013, 93: e27. DOI: 10.1016/j.lfs.2013.12.107.
  • The role of endothelin-1 in the vascular pathobiology of cerebral malariaFreeman B, Dai M, Desruisseaux M. The role of endothelin-1 in the vascular pathobiology of cerebral malaria Life Sciences 2013, 93: e7. DOI: 10.1016/j.lfs.2013.12.045.
  • Alterations in Glucose Homeostasis in a Murine Model of Chagas DiseaseNagajyothi F, Kuliawat R, Kusminski CM, Machado FS, Desruisseaux MS, Zhao D, Schwartz GJ, Huang H, Albanese C, Lisanti MP, Singh R, Li F, Weiss LM, Factor SM, Pessin JE, Scherer PE, Tanowitz HB. Alterations in Glucose Homeostasis in a Murine Model of Chagas Disease American Journal Of Pathology 2013, 182: 886-894. PMID: 23321322, PMCID: PMC3586686, DOI: 10.1016/j.ajpath.2012.11.027.
  • Imaging of Small-Animal Models of Infectious DiseasesJelicks LA, Lisanti MP, Machado FS, Weiss LM, Tanowitz HB, Desruisseaux MS. Imaging of Small-Animal Models of Infectious Diseases American Journal Of Pathology 2012, 182: 296-304. PMID: 23201133, PMCID: PMC3969504, DOI: 10.1016/j.ajpath.2012.09.026.
  • Altered Regulation of Akt Signaling with Murine Cerebral Malaria, Effects on Long-Term Neuro-Cognitive Function, Restoration with Lithium TreatmentDai 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. PMID: 23082110, PMCID: PMC3474787, DOI: 10.1371/journal.pone.0044117.
  • Cerebral Malaria We Have Come a Long WayShikani HJ, Freeman BD, Lisanti MP, Weiss LM, Tanowitz HB, Desruisseaux MS. Cerebral Malaria We Have Come a Long Way American Journal Of Pathology 2012, 181: 1484-1492. PMID: 23021981, PMCID: PMC3483536, DOI: 10.1016/j.ajpath.2012.08.010.
  • Response of Adipose Tissue to Early Infection With Trypanosoma cruzi (Brazil Strain)Nagajyothi F, Desruisseaux MS, Machado FS, Upadhya R, Zhao D, Schwartz GJ, Teixeira MM, Albanese C, Lisanti MP, Chua SC, Weiss LM, Scherer PE, Tanowitz HB. Response of Adipose Tissue to Early Infection With Trypanosoma cruzi (Brazil Strain) The Journal Of Infectious Diseases 2012, 205: 830-840. PMID: 22293433, PMCID: PMC3274374, DOI: 10.1093/infdis/jir840.
  • Gene expression alterations in a mouse model of cerebral malariaDesruisseaux M, Nagajyothi F, Mukherjee S, Iacobas D, Tanowitz H, Spray D. Gene expression alterations in a mouse model of cerebral malaria BMC Proceedings 2008, 2: p15. DOI: 10.1186/1753-6561-2-s1-p15.
  • Thromboxane A 2 is a key regulator of pathogenesis during Trypanosoma cruzi infectionAshton A, Mukherjee S, Nagajyothi F, Huang H, Braunstein V, Desruisseaux M, Factor S, Lopez L, Berman J, Wittner M, Scherer P, Capra V, Coffman T, Serhan C, Gotlinger K, Wu K, Weiss L, Tanowitz H. Thromboxane A 2 is a key regulator of pathogenesis during Trypanosoma cruzi infection Journal Of Cell Biology 2007, 177: i4-i4. DOI: 10.1083/jcb1772oia4.
  • Human Parasitic Disease in the Context of the Blood‐Brain Barrier – Effects, Interactions, and TransgressionsDesruisseaux M, Weiss L, Tanowitz H, Mott A, Milner D. Human Parasitic Disease in the Context of the Blood‐Brain Barrier – Effects, Interactions, and Transgressions 2006, 671-700. DOI: 10.1002/9783527611225.ch27.
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