May 23, 2024 – Cyrianne Keutcha, PhD ’25, has been around malaria all her life, from growing up in a malaria-endemic country, to being infected herself, and now to studying the parasite in the lab. She is completing her degree in the Harvard Griffin Graduate School of Arts and Sciences (GSAS), studying in the Biological Sciences in Public Health program at Harvard T.H. Chan School of Public Health and doing her dissertation research in the lab of Manoj Duraisingh, John LaPorte Given Professor of Immunology and Infectious Diseases.
I was born and raised in Bafoussam, a city in the west region of Cameroon. Malaria is endemic there, so getting it felt like not a big deal—it was like having a cold.
But when I was 11 years old, I got a serious case of malaria. I was hospitalized for about two weeks, and during that time I was first exposed to how infectious and devastating the disease is. I was in a pediatric facility, and I saw a lot of kids come in and out with different infections, but it was mostly malaria. That put a thought in my head—I’m good at science [at school], I don’t want kids to be sick, so I want to be a doctor.
When I was 12, my grandmother passed away from lung cancer. Then two years after, I came to the U.S. Those were transforming stages in my life. It was like I lost my sense of security, a sense of community. Being put into an environment for better opportunity, you have a pressure to succeed. I became very focused, very driven. I graduated as valedictorian of my high school class, was awarded a few scholarships to attend college, and decided to go to Georgia State University.
I was a chemistry major. I always had a love for chemistry. I went in with a pre-med mindset, so I was shadowing doctors, but chemistry has a requirement that you have to do a research class that includes working in the lab, reading scientific papers, and giving presentations. The person who led that class was Prof. Dabney Dixon, who became my undergraduate research advisor. She was working on the infectious disease diphtheria, which impacts tropical areas, including some countries in Africa. That semester was life-changing. There was just something exhilarating about doing research. You might have a 4.0 GPA, and then learn that you do not know much, because textbook knowledge and research knowledge are different. Science will humble you every day of the week. I love to be in a space of not knowing and enjoy the process of learning, thus I took to research.
After my course ended, I kept working with Prof. Dixon, helping to investigate diphtheria-causing bacteria. During my junior and senior years, in between classes, I worked in her lab and contributed to some great published findings in diptheria. Being in a lab was my happy place. The summer before my senior year, I participated in the Amgen Scholars undergraduate research program at Washington University in St. Louis, which was an amazing experience. In my senior year, I was ready to study for the MCAT [the entrance exam for medical school]. I bought the review books, opened them, and just couldn’t focus—I seemed to have lost interest in studying for that path.
Prof. Dixon asked, “Have you ever thought of getting a PhD?” I needed some time to think about it, thus I applied to post-baccalaureate research programs, and I got into the Johns Hopkins Malaria Research Institute. I thought, if I’m going to go into research, I’m going to do malaria—that was my only condition. I’d had it as a kid, and my family back home in Cameroon still gets it every now and then. There’s always this common link between us.
I conducted research for a year at Johns Hopkins under the supervision of Prof. Sean Prigge, and we published our findings on the metabolism of the malaria parasite. Being in the lab was like a playground. I was exposed not only to malaria research, but to public health. I was challenged to think, what does this science mean in the big scheme of the world? What responsibility do you have in making sure that research gets to the people?
In addition to malaria, I wanted to explore other infectious diseases, and the Biological Sciences in Public Health program at Harvard Chan had experts looking at all the diseases that piqued my interest, such as tuberculosis and HIV. So I decided to pursue a doctoral degree here.
After rotating through three labs, I decided to join Manoj’s lab. I wanted to study the malaria parasite Plasmodium falciparum, because that’s the prevalent species in Africa. The parasite has two hosts, Anopheles mosquitoes and humans. When an infected mosquito bites a human, it’s injecting saliva in you, and in that saliva there are parasites. Our lab focuses on the stage at which the parasites invade red blood cells in humans. This stage is essential for parasite replication and responsible for clinical symptoms. Given that I love protein chemistry, I am interested in knowing what kind of protein from the parasite interacts with proteins from the red blood cell to facilitate invasion of the cell.
I’m working on two projects. The first is to develop a human blood cell line that can be genetically modified, so we can test if certain genes affect parasite invasion. To help do this, our lab generated an immortalized cell line—which replicates endlessly—so that we don’t need to keep getting blood from human donors. We use the immortalized cells to make red blood cells, and then perform experiments to see if parasites invade those red blood cells.
The second project is more parasite-driven. My collaborators and I screened multiple parasite lines and identified two that invaded red blood cells using different invasion strategies. We bred those two parasites together and acquired the resulting parasite’s whole genome sequence to identify the specific genomic regions of the parasite responsible for the invasion difference. We identified two genes of interest—one known, so it’s a beautiful control [to show that our experimental system works]. The other is novel, which is the focus of my project. The aim of my research is to clarify the invasion mechanism, with the goal of contributing to the development of a vaccine targeting the stage of infection when parasites are in the blood of the host.
After graduation, I will take a position as a postdoctoral researcher in a lab at the Yale School of Public Health, focusing on vaccine candidates against malaria.
In the future, I hope to work in the global health arena. I have acquired a world of knowledge just by knowing people [who are affected by malaria] and growing up where I did. Often, those bringing public health interventions to a community may make assumptions about the community’s culture and lifestyles.
When I was hospitalized with malaria as a kid, I was privy to something that made me quite sad. Sick kids had to leave the hospital not because they got better, but because they couldn’t financially be there anymore. The second you can’t pay, they ask you to leave the bed. Severe malaria only gets severe because the average person cannot afford to buy the medication. Malaria kills; poverty kills better. It is my opinion that if you can’t eradicate poverty, you will not eradicate malaria.
I have been blessed in my life to be surrounded by amazing mentors—from my parents to my grandparents to my professors. One of my philosophies in life is that the best way to thank people is to do what they have done for you to someone else, to pass it on. That’s why I’m a mentor in the Health Professions Recruitment and Exposure Program [a Harvard Medical School program that provides science lessons and mentorship to Boston-area high school students, particularly those from underserved and underrepresented backgrounds.]
I’m also the vice president and director of diversity and inclusion of the GSAS Harvard Biotech Club [which provides educational and networking opportunities for students interested in working in the biotech industry]. My proudest moment was that, with the MIT Biotech Group, we established a scholarship program to sponsor incoming college freshmen who are interested in life science and hope to someday join biotech. People don’t know how far a scholarship goes. When I started college, I had several, and it’s like somebody said, “I see you. I think you have potential.” Walking into a room, you feel more confident.
– Jay Lau
Photo: Kent Dayton