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.
Corey: What’s the most important part of your role as a trainee? I find it really important to be prepared to try out different methods of managing your activities to find the one the works best for you. There are a lot of different parts of this process, and I think over the course of a PhD you have to learn to incorporate more and more, but it’s not always easy to accommodate for new things or shifts in priorities and to make sure that everything is still working smoothly and effectively overall. And the right balance is almost certainly different for each student, so I think it’s crucial to be trying different strategies and then also to find a means of evaluating the situation so you can keep optimizing. It’s a huge benefit to both you and your mentor to find and recognize explicitly what that optimum is or at least, i guess, where you are relative to it. Let’s not assume that even as a 6th year I’ve managed to solve this puzzle.
Leslie Slota-Burtt interview with second year DSCB student Faraz Ahmed Butt:
ڈی ایس سی بی کے دوسرے سال کے طالب علم فراز احمد بٹ کے ساتھ انٹرویو:
So Faraz, I know you are in your second year of graduate school, but can you tell us a little bit about your research project in the Poss lab and what your scientific interests are?
تو فراز ، میں جانتی ہوں کہ آپ اپنے گریجویٹ اسکول کے دوسرے سال میں ہیں ، لیکن کیا آپ ہمیں پوس لیب میں اپنے تحقیقی منصوبے کے بارے میں تھوڑا بہت بتا سکتے ہیں اور آپ کی سائنسی دلچسپیاں کیا ہیں؟
We are still in the process of molding my project and Ken has been supportive and patient with me. He is helping me incorporate my interests into the project. My interests which are to use imaging tools to observe biological process such as regeneration and development. Therefore, working towards these goals I am developing a fluorescent multicolor labelling system to mark polyploid cells in-vivo. This tool will help provide insight into dynamic roles of polyploid cells in development and regeneration.
میں ابھی بھی میرے پروجیکٹ کو تعمیر کرنے کے عمل میں ہیں اور کین میرے ساتھ تعاون اور صبر کا مظاہرہ کر رہے ہیں۔ وہ میری دلچسپی کو منصوبے میں شامل کرنے میں میری مدد کر رہے ہیں ۔ میری دلچسپیاں یہ ہے کہ حیاتیاتی عمل جیسے تخلیق نو اور نشوونما کے مشاہدہ کے لئے امیجنگ ٹولز کا استعمال کیا جائے۔ لہذا ، ان مقاصد کے حصول کیلیے میں فلواسینٹ ملٹی کلر لیبلنگ سسٹم تیار کر رہا ہوں تاکہ پولیو پلائڈ سیل کو ان ویو میں نشان لگا سکے۔ اس آلے کی ترقی اور تخلیق نو میں پولیپلائڈ سیل کے متحرک کرداروں کے بارے میں بصیرت فراہم کرنے میں مدد ملے گی۔
Can you tell us a little bit about how you went about choosing a lab to join after your rotations, and what advice do you have for first year students going through lab rotations now?
آپ کی روٹیشن کے بعد آپ نے لیب کا انتخاب کیسے کیا ، اور پہلے سال کے طلباء کے لئے آپ کو کیا مشورہ ہے جو اب لیب کی روٹیشن سے گزر رہے ہیں؟
I choose the Poss Lab because of my broad interests aligned with the research being conducted in the lab. It was not just my interests, but I liked Ken’s approach and perspectives towards research.
I would not call myself an expert in giving advice to first year students, but I would say that choosing a lab is a very personal decision. Before deciding talk to people but do not feel pressured by others and choose a lab that aligns with your goals.
میں نے پوس لیب منتحب کی کیوں کہ لیب میں ہونے والی تحقیقات سے میرے وسیع تر مفادات وابستہ ہیں-
میں اپنے آپ کو پہلے سال کے طلباء کو مشورے دینے میں ماہر نہیں سمجھتا، لیکن میں یہ کہوں گا کہ لیب کا انتخاب کرنا ایک بہت ہی ذاتی فیصلہ ہے۔ فیصلہ کرنے سے پہلے لوگوں سے بات کرین لیکن کسی کا دباؤ محسوس نہ کریں اور ایسی لیب کا انتخاب کریں جو آپکی دلچسپی کے مطابق ہو۔
As a former DSCB student looking back, one of the things that stands out to me is the DSCB Colloquium Course. Could you tell us something that is unique to DSCB that you think is valuable to graduate students?
سابقہ ڈی ایس سی بی طالب علم کی حیثیت سے پیچھے مڑ کر ، ایک چیز جو میرے سامنے کھڑی ہے وہ ہے ڈی ایس سی بی کولکیم کورس- کیا آپ ہمیں ایسی کوئی چیز بتاسکتے ہیں جو ڈی ایس کے لئے منفرد ہے جو آپ کے خیال میں گریجویٹ طلباء کیلے قیمتی ہے؟
I agree, the DSCB colloquium has been a unique and valuable experience for me. Reading about research from a new area every week and then hearing about that research for the investigators themselves is very valuable. Furthermore, the smaller group lunches, conversations after their talk and dinners really allowed me to engage in a distinctive manner.
میں اتفاق کرتا ہوں ، ڈی ایس سی بی کالکیوئم میرے لئے ایک انوکھا اور قیمتی تجربہ رہا ہے- ہر ہفتے کسی نئ تحقیق کے بارے میں پڑھنا اور اس کے بعد خود تحقیق کرنے والون سے اس تحقیق کے بارے میں سننا بہت قیمتی ہے۔ مزید یہ کہ چھوٹے گروپ لنچز ، اور ڈنر کے بعد گفتگو نے مجھے واقعی ایک مخصوص انداز میں مشغول رکھا۔
You moved to Durham from Pakistan to start graduate school. Can you tell us a little bit about what is unique about being an international graduate student at DSCB/Duke and what are some of the challenges that are unique to international students?
آپ گریجویٹ اسکول شروع کرنے کے لئے پاکستان سے ڈرہم منتقل ہوے۔ کیا آپ ہمیں ڈی ایس سی بی / ڈیوک میں بین الاقوامی گریجویٹ طالب علم ہونے کے بارے میں انوکھی بات بتاسکتے ہیں اور کچھ ایسے چیلنج کیا ہیں جو بین الاقوامی طلباء کے لئے منفرد ہیں؟
The unique aspect of Duke is the diverse international community which is further supported by the welcoming international house. Moreover, the DSCB program is a smaller yet a very tightknit community. These aspects combined form a very inclusive environment.
In my perspective a challenge for international students is initially keeping pace with other students who are more aware of the system. This initial barrier of bringing myself to pace was a unique challenge for me.
ڈیوک کا انوکھا پہلو اسکا بین الاقوامی برادری ہے جسے استقبال کرنے والے بین الاقوامی گھر سے مزید تعاون حاصل ہے- مزید یہ کہ ، ، ڈی ایس سی بی پروگرام ایک چھوٹی سی برادری ہے لیکن ایک بہت ہی سخت گہری برادری ہے- یہ پہلو مشترکہ طور پر ایک بہت ہی جامع ماحول کی تشکیل کرتے ہیں۔
میری نظر میں بین الاقوامی طلبا کو ابتدائ میں ایک چیلنج یہ ہے کہ دوسرے طلبا کے ساتھ ہم آہنگی برقرار رکھی جاے جو اس نظام سے زیادہ واقف ہیں۔خود کو عملی میدان میں لانے کی یہ ابتدائی رکاوٹ میرے لئے ایک انوکھا چیلنج تھا
It’s so important for graduate students to have interests/hobbies outside of the lab. What do you do when you are not in lab and do you think that helps get through the challenges of graduate school?
گریجویٹ طلباء کےلے لیب سے باہر دلچسپیاں / مختلف شعل رکھنا بہت ضروری ہے- جب آپ لیب میں نہیں ہوتے، آپ کیا کرتے ہیں اور آپ کو کیا لگتا ہے کہ اس سے گریجویٹ اسکول کے چیلنجوں سے نمٹنے میں مدد ملتی ہے؟
Moving for graduate school was the first time I had to cook for myself. I thought cooking would be a burden, but I really enjoy it now. It’s exciting to find new recipes across different cuisines. This is something I really look forward to for the weekend. I think in some sense it is like planning experiments.
گریجویٹ اسکول کے لئے منتقل ہونے کے بعد مجھے پہلی بار کھانا پکانا تھا- میں نے سوچا تھا کہ کھانا پکانا ایک بوجھ ہوگا ، لیکن مجھے اب واقعی مزہ آتا ہے۔ مختلف کھانوں میں نئی ترکیبیں تلاش کرنا دلچسپ لگتا ہے۔ یہ ایسا کام ہے جسکا مجھے ہفتے کے آخر میں انتظار ہوتا ہے۔ میرے خیال میں یہ تجربات کی منصوبہ بندی کرنے جیسا ہی ہے –
If you could tell the 1st year graduate student version of yourself one thing, what would it be?
اپنے تجربے کی بنیاد پر آپ اپنے پہلے سال کے ورژن کو کیا ایک چیز بتائیں گے؟
I would tell myself to interact more with the members of the labs in which I rotated. These interactions not only educated you about people’s projects but also how they find working in the lab. It helps shed light on both the positives and negatives, which I feel is crucial in deciding which lab to join.
میں خود کو کہوں گا کہ میں جس لیب میں روٹیشن کرون اس کے ممبروں کے ساتھ زیادہ سے زیادہ بات چیت کرون۔ یہ گفتگو آپ کو نہ صرف لوگوں کے منصوبوں کے بارے میں آگاہ کرتی ہے بلکہ یہ بھی کہ انکو لیب میں کام کرنا کیسا لگتا ہے- اس سے مثبت اور منفی دونوں پر روشنی ڈالنے میں مدد ملتی ہے ، جو مجھے لگتا ہے کہ کس لیب میں شامل ہونے کا فیصلہ کرنے میں بہت اہم ہے۔
RNI would like to thank past DSCB graduate student (now postdoctoral fellow) Leslie Slota-Burtt, Ph.D. for interviewing Faraz Ahmed Butt. We would also like to thank Riffat Jahan for proofreading the translation into Faraz’s native language of Urdu.
Fei and Hazel are two graduate students from the Developmental and Stem Cell Biology program. Fei works in the Poss lab and Hazel works in the Alman lab. They have very similar cultural backgrounds and a shared interest in regeneration. Despite such similarities, they have distinct points of views in science and life. Today they share their graduate experiences at Duke:
Fei和Hazel是杜克大学发育与干细胞生物学项目的博士研究生，菲在Dr. Poss的实验室工作，Hazel是Dr. Alman实验室的一员。她们具有相似的文化背景，并且都对组织和器官的修复再生有着浓厚的兴趣；但她们对于科学和生活也都有自己独特的视角和看法。今天让我们来了解一下她们在杜克的求学经历。
Why did you choose your current lab?
(Fei) I am attracted to the Poss lab because Ken’s science is really conceptual and pioneering. He always focuses on broad questions and has novel ideas. As a graduate student, I am very lucky to be able to initiate a brand-new project based on my own interest. I have the opportunity to build the foundation of my own project from scratch. In addition, the knowledgeable scientific peers in the Poss lab support me grow quickly as a scientist and give me the confidence to face all the challenges in my research.
我（Fei）对Ken的实验室感兴趣最重要的原因是Ken的研究是非常前沿性的和概念性的。 他专注于大的问题并且总会有一些新奇的点子。我觉得最幸运的是在博士期间就可以根据自己的研究兴趣开启一个全新的课题。 与此同时，Ken的实验室里也有一群知识渊博经验丰富的小伙伴支持着我的快速成长，让我更加有信心面对各种挑战。
(Hazel) I joined Ben’s lab because of his scientific ideas, mentoring philosophy, and the lab environment. As a scientist, Ben always has innovative sometimes crazy ideas that would lead the field to a new direction. As a mentor, Ben encourages and supports me to explore different possibilities in my research as well as in life. He provides the training that would be helpful to me regardless of my career choices. In addition, the Alman lab is like a family that everyone supports and cares each other. I am happy in lab every day.
How are you research experiences in your lab?
(Fei) I started with several projects that have open-ended answers. As a new graduate student, such projects were very exciting, but a bit overwhelming. Through those experiences, I learned to ask key questions, manage my time efficiently, and polish my techniques. My current project started at the end of my third year, which left me limited time to accomplish. However, with all previous experiences and Ken’s support, I am able to move quickly and possibly finish it within three years.
(Hazel) My project focuses on finding therapeutic targets for cartilage tumors. I found that an FDA-approved drug could potentially be redirected to treat these rare diseases. I also found that tumors at different stages could respond to the same treatment distinctively. I also participate in several collaborators’ projects, so that I can work on diverse projects in the field of bone and cancer and build a great publications record.
How do conferences play a part in your graduate school life?
(Hazel) Conferences are very important to my Ph.D. training because I could learn about the most cutting-edge research in my field and get helpful advice and feedback from my scientific peers worldwide. In addition, the friends I made at those conferences have helped me a lot both in my research as well as my career development. I have been to Europe and Asia for conferences, but my most memorable experiences are the three conferences in Galveston, Texas. Fortunately, I was elected to be the Chair of the Gordon Research Seminar in Galveston, so I could benefit my coming scientific peers by creating a welcoming supportive environment for them.
(Hazel) 会议在我的博士教育里有着极其重要的作用。每次开会我都可以了解到领域里最新的进展，并且从全世界的同事那里得到很多宝贵的意见和反馈。而且我在各种会议中也交到了非常多的好朋友，他们不仅对我的科研有所助力，在我的职业发展上也有很大的正面影响。我去欧洲和亚洲都开过会，但是我印象最深的还是三次在德州Galveston参加Gordon Research Conference的经历。在2018年的一次会议中，我很幸运地被选为了这一届会议研讨会的主席，这对我以后职业发展非常有帮助，同时我也帮助我的同事们创造一个良好的互相支持的会议环境，让他们在会议里得到最大的收获。
(Fei) I have been to conferences in Europe and several different places in the US. I agree with Hazel that conferences are really beneficial to my research, especially during the project development stage. A lot of the feedback did integrate into my final project. I especially enjoyed smaller conferences with fewer than 100 people because I could have deep conversations with people. I identified many different personalities among the renowned scientists. I find that the scientific community is very diverse and inclusive, and I feel welcome to be part of it.
(Fei) 我参加过一些在美国以及欧洲举行的学术会议。 我很认同Hazel提到的，这些学术会议对我的科研本身帮助很大，特别是在课题的发展阶段。很多会议上得到的建议都最终融入进了我自己的课题中。我特别喜欢一些小而精的会议，因为在这样的会议上很容易有机会和一些著名的科学家进行深度的交流。我看到了这些科学家迥异不同的性格，并感到了这个学术领域的多样性和包容性。
What do you like doing in your spare time?
(Fei) At Duke, I picked up my music instrument, Gu Qin (an ancient Chinese instrument), after four years of college. I am lucky enough to find a famous musician from China in Cary, NC. I have been polishing my skills and have given many performances in North Carolina with the guidance of her. Music can transcend all boundaries and bridge people with different culture background. I hope I can bring this important part of Chinese culture to more audience in the US and attract more and more people to Chinese history and culture through my music.
(Fei) 来到杜克之后，我捡起了我在大学里丢下了四年的古琴 （一件历史越久的中国乐器）。我很幸运，能够在北卡找到一位来自中国的音乐家。在她的指导下，我开始磨练我的演奏技术并参与了很多当地的音乐演出。音乐可以跨越一切界线，将不同文化背景的人紧紧相连。我希望我能够将中国文化中很重要的这一部分带给更多的美国观众并通过我的音乐吸引更多的人了解中国的历史和文化。
(Hazel) I enjoy doing science education in my spare time. To prepare myself for it, I took the Science Communication course at Duke and served as a teaching assistant for that course afterward. Earlier last year, I gave a small lecture and lab demonstration to a group of underrepresented minority middle school students in collaboration with RNI. This event was to encourage the students to purse research careers in STEM. I also translate scientific articles to Chinese for an online education website Guokr. I think science is more valuable when the public could understand and appreciate it.
How does the Ph.D. training shape you as a person?
(Hazel) I learned to be resilient to failure. Doing research is like riding the rollercoaster, full of ups and downs. I believe the ability to identify the root cause for failure and address those problems will help me succeed in my future life and career. Another important thing I learned from my PhD is self-education. There are a lot of novel techniques and knowledge in all disciplines, especially in the field of research. However, we will leave a school in one day. Being able to find the right resources and self-educate is very important.
(Fei) I learned that process is more valuable than results. Not all the experiments would have expected results. However, I learned to extract useful information from the unexpected ones and solve problems. The skills I gained are more important to the next stage of my life. Furthermore, such experiences give me more courage to face future challenges in my life, because I know that I gain the most from the process.
The three graduate students (Taylor Hinnant, Khanh Vien, and Maya Evanitsky) running DSCB (Development and Stem Cell Biology) recruitment this year interviewed each other about their research, Duke, Durham, and DSCB:
Could you describe your research in a few sentences?
Taylor – I am a second year in Terry Lechler’s lab where I am currently trying to understand how the microtubule cytoskeleton reorganizes during cellular differentiation using the skin as a model system. I am making tools to figure out how the protein composition of the microtubule organizing center in undifferentiated skin cells changes upon differentiation.
Khanh- I’m a second year in Pelin Volkan’s lab investigating the combinatorial code required to appropriately wire and organize the olfactory system in Drosophila.
Maya – I’m a third year in the Di Talia lab using a systems biology approach to study zebrafish scale development. I’m currently looking into the signaling pathways that control when and where scales first form on the fish.
Why did you choose Duke and the DSCB program in particular?
Taylor- I really liked the flexibility in the courses you can take in your first few years in the DSCB program. Also, the friendly environment created by current students and faculty members during my interview made me feel like I was right at home!
Khanh- I chose Duke because I am particularly interested in the mechanobiology involved in the development of biological shapes and Duke has a very strong network of faculty working on the frontier between biology and physics. And I chose DSCB because I love developmental biology, and knew I wanted to go through graduate school with this emphasis.
Maya – I knew when applying to schools that I wanted to study development and to go to a place where people were friendly and collaborative. Duke and DSCB in particular fit all of this and while I’m not doing the kind of genetics work I first envisioned when applying, I’m really happy with the lab I’m in and the research I’m doing.
What is your favorite/least favorite thing about Durham/North Carolina?
Khanh- Many don’t realize this but Durham has an INCREDIBLE history of activism (that still stands true today). I am from Berkeley/Oakland, CA and Durham’s vibrant and diverse community with a progressive social justice mentality helps me feel safe and at home.
Maya – My favorite thing about Durham is honestly just the general vibe of the city. There’s plenty of things to do without it feeling overwhelming. It’s a very friendly city with an interesting history. My least favorite thing is probably the lack of reliable late night public transit. A lot of buses don’t run very late or very often and the only real alternative is driving or getting a Lyft.
What was the biggest hurdle you faced when starting grad school?
Taylor-When starting grad school, I had difficulty managing my time with so many new styles of courses and rotating through labs doing very different types of science. I definitely had to learn to prioritize my time and focus on big goals.
Khanh- I had a very hard time moving away from the tight knit queer people of color community I had. But I am so glad I am learning how to find and build my own community. I am no longer afraid to move anywhere in the world because I know I can find a home.
What advice would you give a student applying to graduate programs?
Khanh- It’s not a race, no one gets a prize for going to graduate school first. Strive to prioritize what makes you happy and surround yourself with people who want this happiness for you.
Maya – Whatever you do, don’t compare yourself to others. Everyone’s journey in science is unique and hits different roadblocks, so don’t think because other people seem so accomplished that you’re not good enough. Also, ask questions about things that matter to you. Whether it’s science policy, sports, outreach, or just finding friends – make sure the school you choose is holistically a good fit for you. We’re in grad school for science, but you shouldn’t give up your life and interests for it.
I received the Duke Regeneration Next Initiative Graduate Student Travel award to attend the 2019 ASCB|EMBO conference in Washington, D.C. this past December. My research interest is in how developing cells and tissues can adapt to challenges such as acute injury and cell loss within the time frame of development. This question is important given that many tissues, such as our heart and limb digits, show little regenerative capacity as adults yet have a striking capacity for regeneration at a young age. Thus, my project aims to understand how injured organs regenerate under time constraints and in concert with development.
My lab previously identified an organ in the Drosophila hindgut that undergoes regeneration at the developing larval stage following acute injury. During the ASCB|EMBO conference, I presented that this regenerative response is time-limited and occurs in concert with development. To accomplish regeneration within developmental time-constraints, I found that hindgut cells accelerate their cell cycles and undergo additional cell divisions to compensate for severe injury. This work introduces a new genetically tractable model to study regeneration under developmental time constraints.
Receiving the RNI travel award and attending the meeting was instrumental to the advancement of both my research and career goals. The meeting allowed me to interact with peers in my field and receive valuable feedback on my work and project directions. The large scope and the high quality and quantity of research of the ASCB|EMBO meeting provided a unique opportunity to expose myself to novel research outside my immediate field – from how tissues and cells interact with each other to the components that makes up the machinery of a single cell. Finally, as a senior graduate student pursuing a career in academia, the RNI travel award provided me with an opportunity to network with potential mentors and peers, as well as to discover new ideas and methods that will be useful for my future career.
Apply for your own travel award by January 31, 2020. More Details here
Tomorrow, countries throughout the world will be ringing in 2020, and over at Duke we can celebrate the four-year anniversary of the official launch of the Regeneration Next Initiative (RNI)! This turn of the decade gives us chance to reflect on and think about the future of the initiative, and the field of regeneration biology. Currently, RNI is led by a committee of co-directors, and works to build a community for and support regeneration and developmental biology researchers at all stages of their careers, in broad areas of expertise. These RNI activities range from student travel grants & post-doctoral fellowships to research conferences, faculty chalk talks, an annual RNI retreat, and to hosting faculty searches. Alongside this work, RNI creates blog posts on the work being done and communicates it to a broader audience through newsletters and social media. An individual that has been with the initiative since its start is Dr. Ken Poss, James B. Duke Professor of Cell Biology and RNI Director. I sat down with Ken and asked him about his past and future perspectives of RNI, the work his lab does, and the impact his experiences have had on him. Check out the interview below.
How did the Regeneration Next Initiative come to be and blossom into what it is today?
It hasn’t changed that much in terms of people since it was launched in the beginning of 2016. We’ve always had the community of faculty studying developmental biology, tissue regeneration, and tissue engineering. And, we’ve always had a focus on the students and post-docs, the various programs, and the labs interested in it. What we didn’t feel we had was a strong sense of community and shared missions, and we didn’t think we were capitalizing on our strengths to build the reputation of the school and have our community flourish as it should be able to.
The School of Medicine ultimately gave us some directive to build a more formalized community interested very broadly in tissue regeneration. It has allowed us to recruit new faculty, gave us funds to invest in people here for post-doctoral fellowships, graduate student travel awards, undergraduate summer fellowships, and various events. . . That’s been the real change: a sense of community, a bit of growth, and a real mechanism of support.
What comes to mind when you talk about regeneration AND developmental biology?
That’s an interesting question because there are many who separate the two, and say that developmental biology might be distinct from regeneration biology. It sounds different, but I equate them. If you think back to studies of regeneration from the mid to late 18th century, these were seminal studies of how hydra regenerate or how salamanders regenerate limbs. It’s fundamental developmental biology for how a tissue forms from the behaviors and division of cells, from a structure that’s ill-defined into a well patterned structure. I see regeneration as a core component of developmental biology.
I also see aging as developmental biology. We’re developing continually, and part of it is through shedding dead tissue or cells and regenerating that. It’s a daily event. As we age we don’t do this as efficiently. This is why the study of embryogenesis, organogenesis, and tissue patterning is an important part of the regeneration community here. I think to understand one, you need to understand the other.
What do you hope to see happen within the initiative in the next five years?
We’ve had great success in stimulating, running, and funding faculty searches. We’ve helped the school invest in six faculty. For four of those faculty, we led and identified the candidate, and successfully recruited them with partnering departments. We’re really happy with the people and ideas that we’ve brought to different parts of Duke! We started off and maybe still believe at its core, that this is a topic where we need to make more discoveries, in most cases, before you can start thinking about therapies.
For many tissues and diseases, more discoveries need to be made on the broad topic of how regeneration happens before you can start thinking about therapies. This is a problem, as some people have jumped onto ideas for therapies that are not based on science. This can be damaging in many ways, mainly to people who think they are being presented with a viable solution.
While there still is a lot to discover, I think we are at a stage now where we’ve engaged multiple aspects and schools here at Duke. Through this, more of the basic scientists and engineers can be thinking about clinical applications and more of the clinical scientists and clinicians can be thinking about how the science is going to inform what they do. I see the next five years as continuing to push the science, but also being more cognizant of the potentials of the field and thinking more about the regenerative medicine space in addition to regenerative biology and discovery science.
Can you give us a snapshot of the range of regeneration research being done in the Poss lab?
My lab is very generally and broadly interested in how and why tissue regeneration occurs. Why it occurs so well in some human tissues (liver, skeletal muscle, blood), why it occurs so poorly in others (the brain, the heart, our limbs), and what explains that. We use the zebrafish, which is particularly good at regenerating some of those structures that we’re bad at. They can regenerate amputated limbs (their fins), severely damaged heart muscle, and a fully severed spinal cord that paralyzes them, which they can regrow and connect from those two severed ends to reverse the paralysis. We study many different tissues in fish. I mentioned the fins, heart, spinal cord, but we also study how they regenerate the bony scales on their surface and their skin that covers those. Recently we’ve been studying their ability to regenerate after a traumatic brain injury.
Studying how regeneration works really well in an animal like the zebrafish, versus a human, gives perspective on what it takes, what the differences might be, and what needs to be tweaked in say a mammal (like a human) to do better at regeneration. Also these other tissues have their own advantages and their own questions. I like to have a wide array of tissues [being researched] so one can see how it seems to be working in one tissue, and can inform the other. Maybe after deep study of these, we can create some kind of common theme or synthesis that explains regeneration better.
How have you seen the research in your lab change as more work is published in other systems?
Regeneration is a more popular and populated field than it was when I first moved here in 2003. Maybe at the time, there were for instance, only two or three groups studying zebrafish heart regeneration. Now there are several dozen. I think for instance, if you think about heart regeneration as a field, the perspective has changed quite a bit with all the groups entering, both in the fish, and prominently with new angles on how the mouse heart can be provoked to regenerate. Back when I started, the predominant idea was that there were cardiac stem cells that exist in our heart, and can and might be normally replenishing the muscle of our heart. And probably one can take these out, purify, expand them, put them back in, and generate a therapeutic regenerative response for the heart. Now, the field has really changed and that has been largely debunked, and a majority of people in the field have different approaches to regeneration.
One of them aligns with how we think about regeneration, in that in mammals there is likely a way to stimulate the muscle cells to divide and to force them with strong molecular controls to participate in regeneration. That I think is really exciting! What comes with this and this increased number people in the field, is that we naturally, as a lab, have turned our attention to thinking about applications as well. How maybe we can take what we’ve learned in fish to understand how the mouse or mammalian heart can regenerate. I think the biggest change has been the density of groups in the field and that for some tissues, like the heart, we may be ten years or less from a regeneration therapy. It’s always important to try and discover new things and be thinking about knowledge and pure science, but there’s no question everyone is also thinking about how are we able to regenerate human hearts today. I think it’s exciting in that respect!
Your lab recently published a piece on limb regeneration for Development’s advocacy collection- how else do you or members of the lab promote regeneration research advocacy?
I think there is never enough done in this arena, and think we need to continue to increase our efforts. That’s something Amy Dickson, who’s the [RNI] Programs Director, is on. We have opportunities to give lectures, for instance to North Carolina teachers, to bring in middle school kids on tours and into the laboratories here. Our undergraduate program takes a handful of students, but the idea is to give people exposure doing research early on, so they get excited about regeneration research. We try to make appearances where it’s important to advocate science generally, when those are happening locally.
We have an opportunity here because this topic is so clearly relevant to how medicine might happen in this century. I think getting more people excited about it as a possible therapy, getting excited about the science, the idea of a career, and just being knowledgeable, is really important, [especially] on what evidence-based science is versus more hopeful, hype-based ideas. That was one of the goals of putting together the Initiative, to get everyone on the same page about what the science behind some of these ideas really is, and what might not be as rigorous. I think as for advocacy, that starts at Duke, but also it needs to eventually branch out and be transmitted because there are a number of “bad actors” out there pedaling therapies that are not therapeutic at all.
How do you balance heading a research lab, being Director of RNI, and having a family?
Balance is a word, on a day to day basis, that’s hard to use, but if you average it over many years, I think I’m happy with the balance that I have. It starts with having really great people and working with great people, both in the initiative and the steering committee we have of co-directors. Then of course in the laboratory where I’ve been very lucky to have a stream of really talented graduate students, post-docs, technical staff, and undergraduate students over the last sixteen years. As a lab PI, (unfortunately most PI’s don’t spend a lot of time doing experiments anymore) I’ve always said the experiments are the most difficult part. Writing grants, giving lectures, and reviewing papers, that’s not nearly as difficult as having a whole set of experiments on your shoulders and having to keep those going every day, to interpret, and to pivot.
I think once you get into a position where you’re able to attract great people, then (for me) I found time to be able to try to serve the school in a different way, and I was (and still am) excited to be able to direct this Initiative. The biggest advantage to me is being able to somehow increase or improve the excitement about this topic I’m really excited about. To have more and more people think about it, come to our events, and agree to come here as new faculty. Once the laboratory becomes populated by great people, then you can find time to do that.
Integrating family time is a real challenge, there’s no real equation or answer for that. It’s been challenging especially in the early years as a faculty member here. I find more time now for my kids who are in high school, but they certainly want less of it than they had when they were younger! That’s a battle a lot of people have, and I think unfortunately it keeps some people away from academia. That balance is truly challenging for many people.
How have you handled being a Packers fan transplanted into the middle of Carolina Panther country?
[Mutual chuckles] Yes, I’m from Green Bay, Wisconsin, and I’ve been a Packers fan forever. My most distinguished position was working during their summer training camps serving food or cleaning up during the meals, and I did that for three or four years.
Green Bay is a long way away from here, but it doesn’t change much over the years. I can only visit once a year at most, but I really like following the team and, when I’m able to watch on TV, seeing the scenes of exciting Green Bay. I don’t know if it’s more the football or just the connection to growing up there, but I find that there are a lot of Packers fans around the country. It’s a nice thing to talk about when you can make that connection!
What do you hope to accomplish in this turn of the decade?
This is kind of my mentality to not to make predictions about, or strict goals, like “we are going to discover this,” or “we are going to help contribute to a therapy.” I hope it’s both of those! We definitely want to continue a streak of finding out new things about how regeneration happens, and we want to be more actively involved in trying to tweak the human regeneration machinery. I think what’s exciting about science and how quickly it moves, is how the tools and technologies come unexpectedly, and they get adopted really quick. We can now do things in zebrafish, like insert any DNA sequence we want, wherever we want in the genome. When I started working with zebrafish, it was only very basic stuff we could do.
I hope we will have a comprehensive understanding of the tissues that we study, and how they regenerate, but I also hope in the next ten years to be surprised by some fundamental concept that we find just find one day assessing the data from an experiment. I like accumulating knowledge and knowing a lot about how something happens, but more exciting to me is just the idea that any day you can find something fundamentally unexpected and important. And that’s just as, or more, exciting. So I hope for more of that!
As the year comes to an end, our Programs Director, Amy Dickson, caught up with Regeneration Next’s first faculty hire, Purushothama Rao Tata, to see how his lab is progressing after 3 years at Duke and whats next for them:
PRT: This is what I tell myself and my trainees – We study one of the most important organs that’s highly vulnerable and affects almost everyone on a daily/seasonal basis. We work towards improving repair of damaged lung tissues and cure lung diseases.
ALD: You have been at Duke for 3 years now. What has been the most surprising aspect of being a PI?
PRT: Yes, it’s been already three years- time flies so fast, particularly when that ticking timer follows you wherever you go. The most surprising thing to me was – how quickly your schedule fills up. My schedule looks almost empty when I look at my calendar a month in advance but surprisingly it fills up in no time. It became more and more obvious when there is a grant deadline. When I was a trainee, all that I had to take care was my experiments and a couple of students who worked with me on the same projects. But now managing the lab members and their projects, managing the budget and other administrative things. Slowly I realized that this is the ‘norm’ and the reality of being a PI. Now, I learn to become more efficient at using my time and doing what I do. Advice from senior faculty and my close interactions with the faculty from RNI affiliated labs helped me accelerate my learning process.
ALD: What is your favorite part of your job?
PRT: The favorite part of my job is when I see a trainee is genuinely excited about his/her data or the next experiment he/she is going to do. I personally know from my own experiences how gratifying/satisfactory such excitement is. The other part I like is – I get to travel and give talks across the globe. I get to meet new people and hear different perspectives about our work etc.
ALD: Of all time, what is the experiment or project you will never forget? Positive or negative!
PRT: It’s not a single experiment or project but it’s a collection of observations. But all of them point to one phenomenon – ‘cell plasticity’. During my postdoc time I demonstrated/learned how plastic our cells are. I still continue to explore this property in everything we do.
ALD: What’s coming up for you? Your lab?
PRT: Many exciting things coming our way in the next one year with some current trainees leaving and some new trainees joining us. Some of our trainees are about to wrap up a couple of manuscripts and they will be ready to move out to explore their own independent research programs. One of the major accomplishments for most PIs is seeing their own trainees move out to build their own nest. I look forward to seeing that in the coming year. Our lab has grown quickly in the last 6 months with the addition of 3 new postdocs. New lab members mean new technical expertise and so new directions. Very exciting times.
– The McNulty lab works with mesenchymal stem cells and meniscal tissue; however, we had not identified the best media to use when performing experiments involving these two different variables. The media used, specifically the use of serum, has significant impact on the results obtained depending on the substances used per experiment, thus, we decided to investigate this more closely in order to establish a favourable culture medium for both MSCs and tissues.
What excites you about your work?
– There are many aspects about this line of research that excite me. I believe that regenerative medicine is the future and getting the chance to work on stem cell therapies for common orthopaedic injuries will be extremely beneficial for patient outcomes and recovery.
Why did you choose to study in Dr. Amy McNulty’s lab for your undergraduate research project?
– Throughout high school I tore my ACL and injured my meniscus twice. The aftermath of these injuries, and the intricacies of the recovery process made me very interested in meniscus repair strategies, and as I researched potential laboratories for my undergraduate research project, Dr. McNulty’s work caught my attention right away.
What has been your favourite experiment in the lab?
– My favourite set of experiments at the lab have been the ones that have used our novel meniscus tissue defect model. Creating this model was tedious, but it allows us to simultaneously investigate many different parameters that promote meniscus repair
What’s next for you? Your research?
– Over the past three years we have worked on optimizing a potential bio scaffold that could be utilized in a clinical setting, but there are many factors that yet have to be studied before that stage can be reached. Currently, I am working on an experiment that combines more clinical parameters, such as dynamic loading. I am planning on working on this project for the remaining part of the year as part of my Senior Thesis project before I graduate in May. After graduation, I am planning on moving to New York and continuing working on this line of research for 2 years before applying to Medical School.