New Diagnostic Tools and Therapeutics for Cerebral Malaria

What are your research interests? 

Cerebral malaria is one of the most severe sequelae of Plasmodium falciparum infection, causing diminished consciousness, seizures and, in many cases, death. Antiparasitic medications are the mainstay of treatment for all forms of malaria; however, there are no adjunct therapies for cerebral malaria, owing to the broad spectrum of brain injuries underlying this condition. In my research, I implement multi-omics approaches to study the pathophysiology of cerebral malaria in children living in areas highly endemic for P. falciparum. I evaluate genomic, transcriptomic and proteomic factors in the human host and the parasite to develop an understanding of why certain patients develop brain injuries, while others do not. Through long-standing collaborations with scientists in Mali and Malawi, we provide diagnostics, therapeutics and cutting-edge science to help the children affected by this disease. 

What is the ultimate goal of your research?  

The goal of my research is to understand the different mechanisms of brain injury that occur in cerebral malaria, and tailor treatment based on the mode of injury. Through work done by some of my collaborators, we know that subsets of patients with cerebral malaria develop ischemia, hemorrhages, seizures and brain swelling. Our goal is to discover diagnostic modalities to readily identify the various types of brain injury in resource-limited settings, and subsequently find appropriate, adjunctive treatments to help treat the disease. 

How did you become interested in this area of research? 

During my medical training, I spent a year as a Fogarty International Clinical Research Scholar in Bamako, Mali, where I took part in my first severe malaria project. My time there was spent doing clinical work at the local hospital and doing research at several malaria field sites throughout the country. The first-hand experience of the devastating effects that malaria can have on vulnerable populations motivated me to pursue this line of research in my career. Since that time, I have continued my collaboration with colleagues in Mali and at the University of Maryland, Baltimore, carrying out projects aimed at understanding the mechanisms underlying this disease, with the ultimate goal of translating this work to therapeutic and vaccine discovery.   

What types of collaborations are you engaged in across campus (and beyond)? 

I am part of the Robert J. Havey, MD Institute for Global Health at Northwestern, where I collaborate with like-minded colleagues interested in international work. Through this network, I began to work with Roxanna Garcia, MD, a colleague in the Division of Neurocritical Care, as we study the management and sequelae of traumatic brain injuries abroad.  

Beyond our campus, my closest collaborators are Mark Travassos, MD, at the University of Maryland, Baltimore, who was a PI for my R25 fellowship work on cerebral malaria, and Nicole O’Brien, MD, and Karl Seydel, MD, PhD, who are renowned malaria experts and great mentors in this field. I also have a longstanding collaboration with Mahamadou Thera, MD, PhD, MPH, of the Malaria Research and Training Center in Mali. Through this network, I can plan and carry out international projects and receive wonderful mentorship at this early stage of my research career. 

Where have you recently published papers? 

I recently published a manuscript entitled, “A shared inflammatory signature across severe malaria syndromes manifested by transcriptomic, proteomic and metabolomic analyses,” in Nature Communications. This work was the culmination of a longstanding international collaboration between myself, a group of Malian scientists from the Malaria Research and Training Center, led by Mahamadou Thera, and a group of scientists at the University of Maryland, Baltimore, led by Mark Travassos.  

We compared the human inflammatory cascades seen in different subtypes of clinical malaria and identified pathways relevant to each clinical trajectory. Importantly, a set of processes and molecules involved in the breakdown of the blood-brain barrier associated with cerebral malaria in transcriptomic, proteomic and metabolomic analyses, providing ample targets for subsequent studies centered on biomarker discovery and prospective therapeutics.  

Who inspires you?  

Aside from those already mentioned, Scott Williams, PhD, a genetic epidemiologist from Case Western Reserve University, continues to be a mentor and an inspiration. Williams was my PhD mentor during my time in the Medical Scientist Training Program at Vanderbilt. He was always immensely supportive of my emphasis on getting field site training and hands-on international work, which helped me fully understand the strengths and shortcomings of some of our projects.  

I did most of my clinical training at Northwestern, so I have numerous mentors in the Ken and Ruth Davee Department of Neurology that have helped me get to this point of my career. John Kessler, MD, and Sam Ung Ho, MD, are an inspiration for their dedication to patients, their teaching of Neurology residents, and their generosity in career mentorship. Dimitri Krainc, MD, has also been immensely supportive of my career, from the very first day when I met him as a rotating away student in Neurology. 

As the most junior member of the Division of Neurocritical Care, I have also been the recipient of wonderful mentorship from all the faculty members with whom I now get to work. They always stood out as exemplary teachers during my training, and I now have the privilege of benefiting from their outstanding collegiality, as well.  

My wife and my mom continue to be a source of inspiration, but we do not have the space for that discussion.