Fikadu G. Tafesse, Ph.D. is an assistant professor of molecular microbiology and immunology who is working to understand how pathogens utilize host cellular processes during infection. He arrived at OHSU from Boston in February, 2016.
Where are you from originally?
I was born and raised in Ethiopia and got my undergraduate degree in agriculture there, learning how to grow crops – basic farming. After graduation, I decided to go to Europe to gain more experience and ended up going to Germany for a master’s degree in horticulture. This was my first introduction to plant biotechnology and for my master’s thesis I worked on a gene family of phospholipases that modify membranes in plants.
I always wanted to go back home to Ethiopia; I never thought of staying in Europe or moving to the U.S. But during the second year of my master’s program, a friend who was getting his Ph.D. in epigenetics asked me to take pictures during his thesis defense. Up to that point, I knew very little about his field but when I heard him talk about DNA methylation and the role it plays in cancer development, I was hooked. In fact, I completely forgot to take pictures because I was so interested in the science! This made me want to go further with my studies before I went back home. I applied to Ph.D. programs and eventually ended up at Utrecht University in the Netherlands. There, I studied under Joost Holthuis and Gerrit van Meer, two lipid biologists. When I joined the lab, I had no idea they were world-renowned because I hadn’t been in the field. I was very fortunate to learn about lipid chemistry and biochemistry from them. I went on to do my postdoc at the Whitehead Institute at MIT and then went to the Ragon Institute at Harvard for more than a year before coming to OHSU.
Tell us about your research and what drew you to it?
Growing up in Ethiopia, I saw many people die of infectious diseases, and as a result I was naturally curious about the biology of these diseases, particularly HIV, tuberculosis, and malaria – the three main killers in developing countries. So, I decided to do my postdoc in a lab where they worked on host-pathogen interactions. That’s why I went to the lab of Hidde Ploegh at the Whitehead Institute of MIT, to work in a lab with immunologists, microbiologists, chemists, and biochemists. There, I learned about viruses, bacteria, and fungi, and my main focus was on how pathogens use the host’s lipids during infection. I then went to the Ragon Institute at Harvard to work closely with the lab of Sarah Fortune and learn about Mycobacterium tuberculosis. Little is known about the role of lipids in bacterial and viral pathogenesis, so I decided to bring what I’d learned in my postdoctoral research to this new line of work.
Human cells are surrounded by membranes, and those membranes contain lipids. Pathogens must cross membranes to infect cells, so what I’m trying to understand is how a virus such as HIV uses the host machinery, especially that of lipids, during infection. A virus doesn’t have machinery of its own, and it uses the host cellular processes for entry and replication without being detected by the immune system. If we can understand the mechanics of this, then we can design a strategy to block it. This is fundamental to combating these diseases.
What are you working on now?
The research focus in my lab is on M. tuberculosis as well as HIV and viruses from the familyFlaviviridae, which includes zika, dengue, and yellow fever. M. tuberculosis is a bacteria that causes tuberculosis. If you look at deaths due to infectious disease globally, tuberculosis is one of the most devastating diseases, especially in developing countries. So I wanted to dedicate my career, in a way, to understanding tuberculosis and HIV-tuberculosis co-infections.
The main reason we don’t know much about lipids and their role in infection is because they are difficult to work with. They are not template coded – there is no DNA that really codes for lipids. They are a bi-product of a series of cellular processes such as metabolism. In research terms, you can’t overexpress it or put a tag on it, so you need a special set of skills to work with and study these metabolites. Most of the techniques we use today to study lipid biochemistry were developed in the 1970s and are very outdated. Since I have strong training in this area, I’m comfortable working on lipids and using various techniques, and I am testing out my initial hypothesis – that lipids are required for bacteria to infect host cells. Our preliminary data strongly suggest they do.
When studying the mechanics of infection by various viruses and bacteria, I ask the question, “Is there similarity between the different pathogens in terms of the way they use these lipids?” This is a very important question, because if there is a commonality, you can develop a strategy that impacts multiple diseases. Finding the answer to that question is my goal.
In addition to my main research program, I’m also developing tools to study M. tuberculosis. The tool I’m developing uses nanobodies, single-domain antibodies that occur only in camelids and sharks. These unique antibodies are extremely small, so they penetrate tissue very well. In terms of their binding, they are as good as conventional antibodies, but they don’t require any post-translational modifications. They’re stable across a wide range of temperatures and in various pH environments. These characteristics make them very easy to work with. My technology development involves generating nanobodies that can be used not only to study the intricate interaction of the bacteria with the host but that also has the potential for diagnostic and therapeutic value. We do this by immunizing Alpaca with antigens such as M. tuberculosis virulence factors, thereby generating nanobodies that target those factors. We then evaluate whether they prevent infection in macrophages. If they have neutralizing capacity, you have a very good candidate to take to the next level of investigation. At this point we have several candidates.
I currently collaborate with folks on the east coast to do the injections, but eventually I want to have an Alpaca farm that I work with here in Oregon. This is one of the programs I really want to pursue because it has very high potential. If you can block that virulence factor, you have a cure. I just want to make a difference. I hope that what I’m doing can have an impact not only in my home country but other developing countries as well. So, I plan to establish collaborations in Ethiopia and other African countries where these diseases are epidemic. It’s important to connect the work to the place where the real problem is – that’s my long term goal.
I was aware of OHSU’s achievements before I came here, particularly in the area of infectious disease such as HIV vaccine development. And with the Oregon National Primate Research Center here, OHSU is a focal point for research into infectious disease in humans. It’s an ideal place to be. On a personal level, as soon as I got here, I really liked the city, the people, this whole region. I knew I could definitely live here, and hey, I’m from Ethiopia – those Boston winters were just too cold for me