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"Speaking of Vitiligo..."

IN HER WORDS – Jillian Richmond

lunes, mayo 11, 2020

Jillian RichmondThis is the 4th in a series of blog posts I’m calling IN HER WORDS, and today will focus on Dr. Jillian Richmond. Dr. Richmond was a postdoctoral fellow in my lab who discovered that resident memory T cells are responsible for relapse of vitiligo after stopping treatments, and that we could target IL-15 to get rid of them and treat vitiligo. She now is an Assistant Professor in our department, and she’s studying other immune-mediated skin diseases like morphea and lupus. She has her own blog that you can read here. In addition to her research program, she has a family, loves to teach students, and is an advocate for women in STEM! She’s a great model for how to be productive and high-achieving, while maintaining a strong work-life balance.

Jillian, when did you first develop an interest in studying skin immunology and vitiligo?
My prior training was in T cell migration and function. As a graduate student, I studied how T cells migrate to the lung and lymph node in the context of tuberculosis infection. I also ran a side project on Cutaneous T Cell Lymphoma (CTCL), which first sparked my interest in skin immunology. There are different subtypes of CTCL which are very interesting: one type of tumor called Sezary Syndrome is a leukemic form, whereas another type called Mycosis Fungoides is like a skin resident T cell. I found it fascinating that these tumors could resemble different types of skin memory T cells, and were treated with different drugs based on their differentiation and migration patterns. They also look very different clinically, and you can observe the disease process happening in the skin without necessarily needing special equipment like you would for internal organs.

I had not really learned about vitiligo until I met you, Dr. Harris. I had been interested in studying autoimmune disease for a while, as I have friends and family affected by autoimmunity. I ended up performing a postdoctoral fellowship in your lab as a result of your collaboration with my prior chemokine fellowship lab, which allowed me to meld my interests and expertise to study vitiligo. I really learned a lot in your lab, and working with you and the rest of the team allowed us to make a lot of progress towards understanding vitiligo. It was an amazing opportunity to perform translational research that may actually help patients, which is ultimately why I chose this profession.

Your research on resident memory T cells in vitiligo has had a huge impact, with a clinical trial on the horizon and a new company that formed around the discovery. When did you realize that your work on this could be so important?
It's funny, I actually feel the least amount of ownership for that project because it was such a team effort. I had wanted to study resident memory T cells in autoimmunity, because the idea is that those are the cells that keep causing flares. But we really didn't know how to get rid of them right away. We tried a few different approaches based on what Laura Mackay and her mentor Thomas Gebhardt had discovered as being important for resident memory T cell development. Our first approach didn't work, but then you met J Yun Tso at a conference and started a collaboration with his and Naoya Tsurushita's company, JN Biosciences, to test the CD122 antibody in the vitiligo model, which blocks IL-15 signaling. We found that the CD122 antibody worked as a durable treatment, and did other studies characterizing what the resident memory T cells were doing in the skin, which ultimately lead to 2 publications. The lab work for the Science Translational Medicine paper on which the trial is based was done in part by me, but I had a lot of help, including PhD student Becky Riding, senior scientist Dr. Xueli Fan, and post-baccalaureate students Lucio Zapata, Madhuri Garg, and Vinny Azzolino. The translational work using human blister biopsies was spearheaded by your MD/PhD student Jim Strassner and millennium PhD student Maggi Ahmed, and the histology studies from traditional biopsies were conducted in collaboration with Drs. Andrea Tovar-Garza and Amit Pandya from UT Southwestern. More recently, post-baccalaureate student Van Kim and physician Zainee Abbas have been performing blistering studies and are managing the trials. So that paper was a result of about 5 years of work, and involved collaborations with people from 2 other institutions, as well as many members of your laboratory. The company and IL-15 clinical trial are really a result of your efforts Dr. Harris, and I wish you continued success and hope that the trial is as successful as our preclinical studies.

But to answer your question, I think it didn't really hit me how important this research project was until I saw the website announcing the upcoming clinical trial sponsored by the ITN. It's awesome that the preclinical science I led in the lab is moving into people. That was one of my career goals, to be able to have a positive impact for patients through my work.

You’ve written a LOT about immunology, vitiligo, and other diseases. What is your favorite article?
My favorite article that I've written is the chemokine review article. T cell migration and function during autoimmunity is what I study and what I love to learn about. My favorite research paper that I've written is the paper about keratinocytes in vitiligo. It's an idea that I had in graduate school - that there is this two-way communication between the immune system and other body tissues during autoimmunity - that I was able to test and demonstrate, at least in one system.

What made you decide to study lupus and morphea when starting your own research program?
I think there is a lot of potential to make a difference in both fields, which is why I've stuck with them. The morphea project started as a collaboration with Heidi Jacobe from UT Southwestern, who approached us when she found the same chemokines we were studying in vitiligo, CXCL9 and CXCL10, were highly upregulated in morphea lesions. Using the tools we had available in the lab, I helped develop a model to test whether they were mechanistically involved in driving fibrosis. I was surprised to find that CXCL9 did in fact drive fibrosis. This has created even more questions that my lab hopes to answer, and in the process, we are hoping to identify new treatment options.

Likewise, the chemokines CXCL9 and CXCL10 are highly upregulated in cutaneous lupus. I am collaborating with Ann Marshak-Rothstein to understand if these are also required for lupus. I will say lupus is much more complicated than vitiligo, there are a lot more cells involved in the process, so it's definitely a challenging puzzle to solve.

You have mentored a lot of students in my lab as a trainee, and also now in your own lab. What made you so interested in mentoring students in research? How did you get involved as a leader representing women in STEM fields?
I've always enjoyed teaching, and research mentoring can be particularly rewarding because not only are you helping someone learn new things, you might be discovering something brand new together!

My passion for research was really instilled in me as an undergrad at Johns Hopkins, which was the first research University in the US. Research lets us understand how things work, why things go wrong, and can help millions when we discover new treatments or technologies. My passion for teaching is a result of my family, friends and teachers, all of whom have helped shape who I am. I was really lucky to be one of the last cohorts of NSF GK12 fellows, which was a partnership that helped teach graduate students how to teach (yes, teaching is a skill that you can learn!) and provided K-12 teachers with a resident "science expert" and role model for their students. It was a very challenging experience, to engage all the students in the high school biology and chemistry courses, but I learned a lot! I think teaching is really under-valued, and taking the time to mentor someone can have a huge impact on their life and the lives of those they ultimately impact.

I sort of fell into women in STEM mentoring as a result of one of my former students, Senegal Carty. Senegal performed a portion of her Master’s thesis research with me in the lab, and is now pursuing her PhD at Boston University School of Medicine, which is also my Alma mater. She invited me to speak at a "She Inspires" lunch, which was mostly a format to speak about my own career trajectory and then to answer questions from the students. A lot of the questions I got were related to starting a family (when is the right time, how do you continue in your career with young children), I think as a product of the fact that the average age at time of PhD/postdoc training is near the time that many people want to start a family. Unfortunately, there are no easy answers, and each family is different, but at least shared experience is a place to start. I was also pleased to hear that Postdocs for Change was able to advocate for NIH eligibility extensions for parents, so I think we are moving in the right direction. There are lots of resources available to read online including Science Careers, and even academic Twitter (follow @virusesimmunity), and I am always open to answer questions (email is the best way to reach me).

How did you remain productive after starting your family?
You know that saying "it takes a village to raise a child"? That's about right. My husband is an equal partner in our marriage and we take turns with the kids and housework. My parents and in-laws (who all still work) help with child care, and my kids go to daycare (they have awesome teachers!) 3 days a week. I've been able to stay home with them one day a week since birth by reducing my effort, in part due to the American Skin Association for which I'm very grateful, and because I have a working spouse. Part of the decision to go part time was financial (full time daycare is expensive, though rightfully so; it would have been a wash for us). But I also felt strongly about spending time with my children while they were so little, to make sure I was present to build a good relationship base with them before they are school-aged and attend full time. And truly being present and spending time with them is a joy, but sometimes feels like a job (and it is a job for early childhood educators). As Frederick Douglass said, "it is easier to build strong children than to repair broken men." Breastfeeding, a biological relationship between mother and child, is also easier when you are together (fed is best, but there are immunological benefits to breastfeeding that, as an immunologist, I couldn't ignore. And no, pumping is not the same, though I did this too when I was back at work). So, it's not just me, and I realize I'm very blessed to have the support of these awesome people. I hope that my kids benefit from this approach too, as they say "variety is the spice of life"!

As for lab, I put in long hours and generated a ton of data before maternity leave so that I could do more analysis and writing after I had my first child. This worked for me, though I realize not everyone can do this. I was also a senior postdoc at the time, so I had taught a lot of people in the lab and they were gracious enough to help run experiments while I was on maternity leave. At some point I needed to go back to running experiments; those days can be hard because I end up staying later, which means my husband has to take care of the kids. But around that time, I was awarded 2 compatible grants and promoted to a faculty position. I was able to hire my own technician, Colton Garelli, who is awesome and helps me run my lab.

Another thing about being productive- I've always tried to work smarter not longer: I graduated undergrad in 3 years and my PhD program in 4 years with 4 first-author publications. I think I've unconsciously been practicing the same "intense" work followed by rest or a different activity that Charles Darwin, Teddy Roosevelt and others have done. When applying this to academic research post-children, I do email in the morning before my kids wake up, and I do analysis and writing during nap time. In lab, this means doing literature reviews or writing a portion of a grant while an assay is incubating. Some experiments can be broken up over several days. I don't think there is one magic formula that will help everyone though, you need to play to your own strengths and find what works for you.

How have you stayed productive during COVID19?
On the subject of COVID19, I first want to thank all of our frontline health workers, food & supply chain workers, and other essential personnel for all that you are doing. I also want to give my condolences to everyone who has lost friends, family members, colleagues, during this pandemic.

I suppose my being home with the kids part time helped prepare me a little for COVID19 remote work, though to be honest it is more difficult being home 5 days. I think an important thing for my colleagues with small children at home is to change your perspective from working in solid time blocks to partial blocks with breaks for spending time with the kids. I work during nap and before they wake up in the morning, and my husband and I take shifts for the remaining time (he is considered essential personnel). I read while the kids play independently, and sometimes they like to pretend they are doing work like me by drawing while I type. In between periods of work, we try to stay active by going outside, doing yoga or other exercises together, or being creative through play, cooking or art. We’ve even done a few science demos (thanks Nitya Jain!). In terms of other resources to check out, there’s a bunch of cool demos at Raising DaVinci, and for older students, there’s Skype a Scientist, SciShow, and others. It’s also good for kids to be bored once in a while, though admittedly I have a hard time with that.

Have you been participating in any activities specific to COVID?
To help fight COVID19, I signed up for Crowdfight COVID19, which partners volunteers with COVID researchers to help facilitate research. I’ve only had one task so far, but hoping to contribute more! I have been running Folding at Home and Boinc on my computer, which uses extra GPU/CPU to run simulations to fight COVID. And I’ve donated to charities supporting various aspects of our communities during COVID. My amazing medical research student Haya Raef has spearheaded an effort with her clinical research mentor Dr. Jennifer Tan to make COVID care packages for the homeless communities in Portland, ME and Boston, MA. I played a small role in this effort, but I am glad to be able to help them make such an important contribution. 

For those of you who are non-essential like me and are looking for additional ways you can support COVID19 efforts beyond social distancing, you can check with your local and state agencies or institutions to see what opportunities are available (see for example MA state and Worcester COVID19 volunteer pages.

Any other thoughts?
Lately I’ve been thinking a lot about ways to make research greener. Biomedical research generates biohazard waste, which ultimately impacts the environment. Since we know environment can have a big influence on development of diseases, I think it is really important to try to minimize waste streams in the labs we are working in to cure said diseases. This can also help with revenue. So far, we’ve switched from one-use plastic syringes to reusable metal syringes for dissociating tissue for flow cytometry analysis. And we have started participating in the chill-up freezer challenge. COVID19 has forced us to switch to teleconferencing, which cuts down on travel to save money and reduce carbon footprint. I think this will also open up more opportunities for less affluent scientists (both in terms of country and individual socioeconomic status) and scientists who have family/care obligations to attend scientific conferences, serve on grant review panels, and give seminars. 

I’m looking for new and creative ways to make our research more streamlined and efficient, and I’d love to hear ideas from others to move forward in these endeavors!