“As science often does, it surprises, and so what we found was…”

Amanda MacLeod, M.D.

Amanda MacLeod, M.D.

MAX_20200109 2small follicles near wound Physician-Scientist Amanda MacLeod, M.D. is an Associate Professor of Dermatology.  She will be hosting our faculty chalk talk this month and gave us some insights into her lab and her life as a physician-scientist:

 

Research in the MacLeod laboratory is focused on innate antimicrobial immunity in the skin. Our emphasis is to better understand host-microbial interactions and immune functions during skin barrier regeneration, infections, allergic responses, and cancer. We are very interested in understanding how innate antimicrobial peptides and proteins including antiviral proteins are regulated, what drives their expression and what roles they play in the skin.

– What drove you to be a physician-scientist?

I always had an inherent love for medicine and science from very early age. This is surprising because no one in my family was a doctor nor scientist. But somehow, I knew that a medical and scientific career would provide me with a fulfilling journey of biomedical discovery. With my biomedical training and experience from Germany and the US, I have a unique perspective to research that is greatly inspired by medical patient care and human diseases (even though I do not see currently patients anymore). In addition, as an academic Physician-Scientist, I have the honor and opportunity to train what I believe will become the best cadre of our next generation of (physician-)scientists.

In addition, one of the amazing effects of being an academic physician-scientist is the fact that you get to work and collaborate with excellent members of the scientific community, locally, nationally and internationally, not only scientists and physicians but many different professions who together are the best collaborators and contributors to our research projects.

– Who is your science hero?

I have many science heroes and I have been very fortunate to work with many incredible (physician-) scientists during my training and beyond. One of my very first research mentors and science heroes was my MD thesis advisor and diabetes immunotoxicologist, Dr. Helga Gleichman.  I had two outstanding postdoc advisors, Dr. Richard Gallo from UCSD and Dr. Wendy Havran from The Scripps Research Institute. Dr. Gallo is a top innovative physician-scientist and one of the most cited and impactful researchers in the dermatology, cutaneous microbiome and antimicrobial innate immunity worlds. He is the founding department chair of Dermatology at UCSD and my time in his laboratory was just fantastic. Dr. Havran was a legendary figure in the gamma delta T cell field and a top-regarded immunologist. Wendy trained with Jim Allison, and she sadly passed away just a couple of months ago. Dr. Russell Hall, chair of the Duke Dermatology Department has been, and continues to be an amazing mentor and scientist and has had great impact on my scientific successes since the very beginning of my faculty appointment here at Duke.

– Do you have any interesting outside of work activities?

I like to spend time with my family including our two sons. I like to be very active and enjoy playing tennis, riding horses, go on hikes and swim. I love my yard work and building projects around the house. If I find enough time I really enjoy painting, too. I also try to do good in our Durham and Triangle community, including health education and fundraising for our public schools.

– What is your favorite part of your job?

I thinking mentoring trainees and see them grow while making new basic-science discoveries that hold promise for translation are the favorite parts of my job.

In this regard, I really enjoy conceptually connecting research discoveries from the cutaneous regeneration, infection biology and immunology sides and making scientific impact not only in these respective fields but also beyond, including infectious disease biology, aging, pediatrics, cell biology, neuro-immunology and other research areas.

I greatly enjoy mentoring students and trainees. I often pause and take a look back to reflect on my experiences as a mentor and the factors that I believe contribute most to the success of trainees as independent scientists and professionals. I find that activating self-motivation, confidence, trust, and creativity are very important. Besides of being a model leader who seeds ideas, I like to create environments to foster trainees to generate and execute their own ideas. Once this happens, it is the best reward you can get as a mentor.

In addition, I find that a highly beneficial skill for an independent (physician-)scientist career is to have both the ‘scientific-mathematical’ and the ‘artistic’ senses. These senses, I believe, help being successful and to develop high rigor, inquiry and investigation aimed at solving one single scientific problem while also being able to keeping in view the vision and creativity to think outside the box, trust your ‘inner voice’, and seeing bio-medical problems holistically and globally. I think that this helps to achieve extraordinary results and bringing out the best innovative scientific minds in physicians and scientists alike.

– Of all time, what is the experiment or clinical experience you will never forget?

Scientifically, I will never forget how our research on innate antiviral immunity began in the MacLeod lab. We had started an exciting project on skin wound healing and were planning experiments with human epithelial skin cells, called keratinocytes, and a cytokine that we had just discovered to have important roles in wound healing. The goal was to simply assess the effect this cytokine would have on cutaneous innate antimicrobial peptide and protein responses. This was relevant to the project, as we knew that these epithelial cells with stem cell potential were pivotal in regenerating and closing a wound defect of the skin; and the next step was to define whether this cytokine was also able to activate innate antimicrobial defenses to protect the skin wound from becoming infected. I remember how our aim was to design and gear this experiment to show that this cytokine in fact was able to activate typically innate antibacterial immune responses and so we included an antiviral genes as a “negative control”. As science often does, it surprises, and so what we found was that this cytokine of interest actually activated to a very great degree the gene transcript encoding for an antiviral  protein. This is how a major line of investigation in my laboratory was born.

All our members in the MacLeod laboratory are all so excited to work on these innate antiviral immune pathways and linking them to the regenerative capacities on skin stem cells as well as non-classical skin functions in antimicrobial defense. Our research shows such great significance and promise in various infectious diseases, skin inflammation and other conditions. Lessons we learn may be applicable to other epithelial barrier tissues, harboring similar to the skin adult stem cell pools and immune cells in a tightly controlled niche.

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