Autophagy and Immunopathology: A Conversation with Ranee Aflakpui, PhD Candidate

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Autophagy and Immunopathology: A Conversation with Ranee Aflakpui, PhD Candidate

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Ranee Aflakpui, MS, a third-year PhD candidate in the laboratory of Fernando Macian-Juan, MD, PhD , is training for a career in immunology research. Ms. Aflakpui came to Einstein in 2017 and joined the Macian Laboratory in 2018.

“Ranee is one of these persons that makes the lab seem full of life. She is kind and full of energy and a pleasure to work with,” says her mentor, Dr. Macian. “She’s a very smart student with a genuine passion for research. I have no doubt that those qualities, together with her curiosity, incredible work ethic and perseverance, will lead her to very successful career in science.

I feel fortunate that she decided to join my lab, where she is unveiling novel mechanisms that control the function of regulatory T cells, a crucial cell for the maintenance of immune homeostasis and the prevention of autoimmunity.”

We recently sat down with Ms. Aflakpui to talk about her life, her research, and her career path.

Ranee Aflakpui
Ranee Aflakpui at work in the lab.

To “set the stage,” please share a bit about your family background. Where did you grow up? Who were your early role models?

Well, I grew up in Accra, the capitol city of Ghana, in West Africa. I was raised by my paternal grandparents.

My grandmother had no formal education, but she was the best. Whenever I achieved something in school, she would ask about its significance, and once I explained it to her she would say, “Well done! Good job!” She was always there for me.

My grandpa was a clerk. He is a very focused person. He’s very time-conscious and goes to bed early. He always motivated me when I was young. He taught me that the arc of your life depends on you, and to always make sure to do the right thing at the right time.

Growing up, I learned to be very independent. I taught myself many things, and learned to do my homework by myself. But I was really fortunate. My grandparents were very nurturing. They inculcated a strong work ethic and good values in me.

Your research focuses on a biological process called autophagy. What is autophagy?

Autophagy is a “self-eating” evolutionarily conserved cellular process through which damaged or abnormal organelles and proteins in the body are degraded. It serves as a quality-control mechanism to maintain cellular homeostasis and proper functioning of the body. In other words, autophagy acts like a “garbage disposal.” It’s the body’s way of cleaning out damaged cells to make way for new, healthy cells.

What is the goal of your research project on autophagy and regulatory T cells?

Scientists have discovered that targeted degradation by autophagy is also able to regulate several functions of our immune system. My project is aimed at understanding the role a type of autophagy called chaperone mediated autophagy, or CMA, plays in regulating the differentiation and function of regulatory T cells, or Tregs.

Tregs are a component of immune cells that are important in regulating or suppressing other cells in the immune system. They control the immune response to self and foreign particles, and help prevent autoimmune diseases such as diabetes, inflammatory bowel disease and multiple sclerosis.

Conversely, Tregs’ suppressive effect can be detrimental by preventing anti-cancer immune responses as well as immunity to some pathogens including Plasmodium, which causes malaria, and Mycobacterium tuberculosis, which causes tuberculosis. I’m using mouse models to understand how the absence of CMA in Tregs impacts their development, differentiation and suppressive function.

What is the potential clinical significance of this research?

Dysregulated autophagy has been identified as a major cause of several diseases, and there is a growing interest in therapies that can be used to target autophagy. By identifying the specific mechanisms by which CMA regulates Tregs, we can identify potential targets that can be used therapeutically to modulate the “double edged sword” function of Tregs in order to prevent autoimmunity or boost anti-tumor immune responses.

What aspects of your work do you find the most challenging and/or exciting?

I find it interesting that I am able to study these cute little rodents to understand what happens in humans. Breeding the mice takes time, so that can be a challenge. But I’m always looking forward to the results. Knowing you are the first person to see A, B or C – or whatever you hypothesize—feels good after so many trials, especially when things go your way. It’s very exciting. Usually, the first trial doesn’t work, so you have to keep troubleshooting. Working with senior people in the lab is great. It’s like having a special lecture or mentoring session. Sometimes they push you to do further reading. It becomes an educational experience.

Where did you study and what degrees did you earn before coming to Einstein?

I earned my bachelor’s degree in Biochemistry at the University of Ghana. After that, I obtained my master’s in Molecular Cell Biology of Infectious Diseases from the same university. However, my master’s research was performed in the laboratory of Dr. Anthony Baughn at the Microbiology and Immunology Department of the University of Minnesota Medical School, where my research focus was understanding the mechanism of pyrazinamide (first-line drug for treating TB) resistance in Mycobacterium tuberculosis.

What made you decide to pursue your master’s research in the United States?

Research comes with lots of challenges in Ghana. Resources and equipment are very limited. I wanted to enjoy doing research and wanted to be exposed to so much, including skills like grant writing. So I wrote to 30 professors in the U.S. and two responded, one of whom was professor Baughn. I had an uncle who lived in Minnesota and I was able to live with him.

Why did you choose Einstein for your doctoral studies?

I loved the multidisciplinary aspect of the doctoral program here. I was most excited about the fact that you’re exposed to diverse scientific fields, you have the flexibility of rotating in the laboratory of well-established professors in any department of your choice, and then finally carving your own research niche. The affordable housing and proximity to campus was also a number one factor.

Please describe what it’s like to work in Dr. Macian’s lab.

Dr. Fernando Macian is a great mentor and advisor. He has an open-door policy and he’s constantly available and always happy to help answer scientific questions and troubleshoot experiments. He’s not only concerned about my academics, but about my mental, physical and family life as well. My lab colleagues are really smart and friendly, making the laboratory environment serene and conducive for research.

What is your ultimate career goal?

My goal is to become a research scientist, either in academia or in industry, in the field of immunotherapy.

What made you choose this particular field of research?

I chose this field because in my view, it’s just fascinating to know that, regardless of the pool of pathogens and toxins we find ourselves swimming in each day, our immune system works tirelessly to keep us healthy and is crucial for our survival.

What inspired you to go into biomedical research?

I was a curious child. I liked to talk and asked many questions. In Ghana, once you finish junior high school, you take a national standardized high school entrance exam. If you do great on your exam they put you in the “smart” track, which is science. Most science-track students want to become medical doctors because that’s all they know about, and it’s prestigious. You start as a biological sciences major and from there you go to medical school.

I didn’t make the first cut, but I could still choose from several options, including biochemistry. While studying biochemistry during my last two years of undergrad, I realized that research was another route to a professional career. Everyone in my family was disappointed that I wasn’t going to become a physician but I was confident and knew what I wanted to do.

You participated in Einstein’s first-ever “Women in Science” day in February 2020. What were some highlights for you?

The program was a real eye-opener. I got to understand that although the field of biomedicine is currently dominated by men, this should not deter me from making it to the top in my career. I learned the importance of self-advocacy and of letting everyone around me know that regardless of the fact that I am a woman, I can be competent in any area in which I find myself. Hearing the stories of very prominent women in biomedicine was very encouraging. Finally, the event served as a great avenue to meet and network with other like-minded women.

As an immunopathologist-in-training, what are your thoughts on the COVID-19 pandemic?

This pandemic has been a very challenging time for the whole world. But then, it gives us an opportunity to appreciate the importance of scientists. It’s very exciting to know that everyone, including physicians and healthcare professionals, are looking to scientists to understand the biology and pathophysiology of COVID-19. Currently, immunologists are working tirelessly to come up with a vaccine that will benefit the whole world. Indeed, I feel so privileged for choosing this career path.

[At this writing] the cases in Ghana are increasing. We have over 9,000 cases. However, the deaths are about 50 and recovery is almost 4,000, which is good. The main testing center in Ghana, Noguchi Memorial Institute for Medical Research, is located on the University of Ghana campus. I interned there while working on my bachelor’s and master’s degrees.

Your training has placed you at the intersection of two pandemics. The Bronx was the early epicenter of the COVID-19 crisis; and Minneapolis, where you did your master’s research, became the epicenter of the movement for racial justice sparked by the death of George Floyd – a movement that seeks to address what many in our Einstein Montefiore community view as the public health crisis of racism.

I was very sad when I watched the video and I was really heartbroken because it happened in Minnesota. All my friends are aware that Minneapolis is my American hometown. So people kept texting and asking if I had heard what had happened there. I was very disappointed, because I have many friends there and they are extremely nice people. Seeing all those shops that I had once passed by or bought stuff from getting destroyed was sad. I do not support violent protests, but I feel people have had enough of the racial injustice, and we can see the support all over the world. I just pray this incident will really be the game changer.

Did you participate in the moments of silence observed by the Einstein Montefiore community on June 5, in honor of Mr. Floyd and in solidarity with the Black Lives Matter movement?

Yes, I did. Kneeling for nine minutes was not an easy thing to do. When I was kneeling, all I could imagine was the pain George Floyd had to endure that whole time. I was just kneeling on one knee, and it was not a pleasant experience. You can imagine kneeling on someone's neck. Being a person of color, I’m very impressed at the massive support we’re getting from people of all races and colors. It makes me know that we are not alone in this. I’m very hopeful that a lot will change as a result of this incident.

That same day, Ghana held a memorial service [at the WEB DuBois Centre for Panafrican Culture in Accra] in honor of George Floyd and all who have lost their lives due to racial injustice. Last December, a year of return was held in Ghana and people of African descent attended from all over the world. So it was nice they held a memorial service there for George Floyd to show their solidarity.

To wrap up on a lighter note, how do you like to spend your time when you’re not working in the lab?

I enjoy cooking Ghanaian dishes like jollof rice, goat soup, waakye (rice and beans), banku and okra stew, for myself and my friends; attending activities in church; and listening to and singing Gospel music.