Spotlight Archives

2018 - Kristen Naegle

naegle.jpgKristen Naegle, PhD

Assistant Professor of Biomedical Engineering
Assistant Professor of Computer Science and Engineering
B.S. (Electrical Engineering), University of Washington, 2001
M.S. (Electrical Engineering) University of Washington, 2004
S.M. (Bioengineering) Massachusetts Institute of Technology, 2006
Ph.D. (Bioengineering) Massachusetts Institute of Technology, 2010
What do you enjoy most about being part of the Washington University DBBS team?
I immensely enjoy interacting with the students of DBBS and colleagues affiliated with DBBS who are doing so much diverse and interesting research in a collaborative manner.
What are your research interests? What are your research goals?
I am interested in understanding how tyrosine phosphorylation functions within proteins and within cell signaling networks. There are 46,000 phosphotyrosines that have been identified in the human proteome (currently) and my goal is to develop both computational and experimental approaches to identify and test the function of phosphotyrosine -- specifically developing methods and understanding that begins to approach the scale of the problem.
How has your time at Washington University helped further your research goals?
I have had amazing students and staff, great colleagues, and fabulous facilities that have allowed me to establish a research program and build into new areas. I would not have guessed five years ago that I would be publishing an algorithm in evolution and developing synthetic biology approaches to producing phosphorylated proteins in E. coli.
What is your favorite part about living in St. Louis?
I grew up in a truly small city (Boise, Idaho) and most recently lived in a big city (Boston, Massachusetts). I really appreciate how St. Louis is a blend of both of these types of metropolitan areas.  It has all of the trappings of a larger city (theater, opera, museums, gardens, and great food), but with the expense and ease of access as a small city.
What hobbies do you enjoy?
My husband would tell you that my hobby is trying new hobbies.
What is your favorite quote?
Zora Neale Hurston is my favorite author and it's for reasons like these (from “Their Eyes Were Watching God”):
"She was a rut in the road. Plenty of life beneath the surface but it was kept beaten down by the wheels. Sometimes she stuck out into the future, imagining her life different from what it was. But mostly she lived between her hat and her heels, with her emotional disturbances like shade patterns in the woods — come and gone with the sun."
A second quote, a line that will haunt me the rest of my days is from Ta-Nehisi Coates' "Between the World and Me"; a letter to his son: "Never forget that we were enslaved in this country longer than we have been free. Never forget that for 250 years black people were born into chains — whole generations followed by more generations who knew nothing but chains.”
What is the most ridiculous fact you know?
I know that there is an animal in Asia, the bearcat, whose urine smells like hot buttered popcorn. Also, octopuses don't stick to themselves because of a process (likely chemical) between their skin and their suckers.
Who is your biggest role model?
I try not to judge people by their size.
What advice would you give to both prospective and current graduate students?
To prospective students: There is never one path and don't believe people when they tell you there is a best path.
To current graduate students, if you haven't yet: Cultivate your communities — the scientific community that will push your boundaries and keep you curious every day and the personal community that will support you every step of the way and keep you rooted in what is truly important. 
Fellowships, awards, and publications while at Washington University:
NCI/SAGE Integrative Approaches to Cancer Metastasis workshop, June 2017 (invited participant)
Publication Ronan, Qi, and Naegle in “Science Signaling” made the home page of science and was the most tweeted
article in the history of “Science Signaling.”
Publication Ronan et al. in “Journal of Biological Chemistry” was article of the week, a highlight of the year in 2016, and rated "Exceptional" by Faculty of 1000.
Keynote Speaker, 4th Midwest Quantitative Biology Symposium, Purdue, October 22, 2016.
Keynote Speaker, Biomedical Computation at Stanford (BCATS) Symposium, April 6, 2015.
1.         Sloutsky, Roman, and Kristen M. Naegle. “Accuracy through Subsampling of Protein EvolutioN: An Ensemble Approach to Testing Accuracy and Reconstructing the History of Protein Family Divergence.” (BioRXiv Preprint: doi:, 2017)
2.         Sloutsky, Roman, and Kristen M. Naegle. “Proteome-level analysis indicates global mechanisms for post-translational regulation of RRM domains”. Journal of Molecular Biology, 2017
3.         Mooradian, Arshag D., Jason M. Held, and Kristen M. Naegle. “Using ProteomeScout: A Resource of Post-Translational Modifications, Their Experiments, and the Proteins They Annotate.” Current Protocols in Bioinformatics, 2017
4.         Schaberg, Katherine E., Venktesh S Shirure, Elizabeth A Worley, Steven C George, and Kristen M Naegle. “Ensemble Clustering of Phosphoproteomic Data Identifies Differences in Protein Interactions and Cell-Cell Junction Integrity of HER2-Overexpressing Cells.” Integr. Biol. 9 (2017): 539–47. doi:10.1039/C7IB00054E.
5.         Sloutsky, Roman, and Kristen M. Naegle. “High-Resolution Identification of Specificity Determining Positions in the LacI Protein Family Using Ensembles of Sub-Sampled Alignments.” Plos One 11, no. 9 (2016): e0162579.
6.         Noren, David P., Byron L. Long, Raquel Norel, Kahn Rrhissorrakrai, Kenneth Hess, Chenyue Wendy Hu, Alex J. Bisberg, et al. “A Crowdsourcing Approach to Developing and Assessing Prediction Algorithms for AML Prognosis.” PLOS Computational Biology 12, no. 6 (2016): e1004890. *Naegle lab (Tom Ronan, Jennifer Flynn, Kristen M. Naegle) participated as a team in the AML consortium.
7.         Ronan, Thomas, Zhijie Qi, and Kristen M Naegle, “Avoiding pitfalls when clustering biological data”, Science Signaling, 9, no. 432 (2016): re6. Invited Review.
8.         Ronan, Thomas, Jennifer L. McDonnell-Obermann, Laurel Huelsmann, *Kristen M. Naegle, and  *Linda J. Pike. “The seven EGF receptor agonists each elicit a unique signature of recruitment of downstream signaling proteins”, Journal of Biological Chemistry 291, no. 12 (2016): 5528-5540 *co-corresponding
9.         Holehouse, Alex S, and Kristen M. Naegle. “Reproducible Analysis of Post-Translational Modifications in Proteomes—Application to Human Mutations.” PLoS ONE 10, no. 12 (2015): 1–19.
10.       *Naegle, Kristen M., Nancy R Gough, and *Michael B Yaffe. “Criteria for Biological Reproducibility : What Does ‘n’ Mean ?” Science Signaling 8, no. 371 (2015): 2–5. *co-corresponding
11.       Matlock, Matthew K, Alex S Holehouse, and Kristen M Naegle. “ProteomeScout: A Repository and Analysis Resource for Post-Translational Modifications and Proteins.” Nucleic Acids Research 43, no. D1 (November 20, 2015): D521–30.
12.       Cho, Yongcheol, Roman Sloutsky, Kristen M Naegle, and Valeria Cavalli. “Injury-Induced HDAC5 Nuclear Export Is Essential for Axon Regeneration.” Cell 155, no. 4 (November 2013): 894–908.
13.       Iwai, Leo K, Leo S Payne, Maciej T Luczynski, Francis Chang, Huifang Xu, Ryan W Clinton, Angela Paul, Edward A. Esposito, Scott Gridley, Birgit Leitinger, Kristen M Naegle, and Paul H. Huang.  “Phosphoproteomics of Collagen Receptor Networks Reveals SHP-2 Phosphorylation Downstream of Wild-Type DDR2 and Its Lung Cancer Mutants.” The Biochemical Journal 454, no. 3 (September 15, 2013): 501–13.

14.       Sloutsky, Roman, Nicolas Jimenez, S Joshua Swamidass, and Kristen M Naegle. “Accounting for Noise When Clustering Biological Data.” Briefings in Bioinformatics 14, no. 4 (July 2013): 423–36. doi:10.1093/bib/bbs057.

2017 - William Gillanders

William Gillanders

The physician-scientist and avid cyclist is keeping the wheels turning in the race against breast cancer 

By Jim Goodwin
Photo by Robert Boston

William Gillanders, MD, is developing a vaccine aimed at harnessing the immune system to fight breast cancer. If proven effective as a cancer treatment, the vaccine someday could be used to prevent breast cancer, too.
It might not be the perfect metaphor, but science and cycling have some things in common. They can be grueling or exhilarating, depending on where you are in the process.
Both require hard work and determination. And like cycling, science can be an individual and team endeavor at the same time. William Gillanders, MD, knows these things firsthand. He’s not only a Washington University breast surgeon at Barnes-Jewish Hospital and Siteman Cancer Center, but an avid cyclist. The 49-year-old pursues both interests daily and often finds ways in which they intersect.
“There is a metaphor there,” he said. “My goal is to change breast cancer treatment paradigms, to make vaccines a reality for women who are being treated for breast cancer. That’s an ambitious goal but one that I think I can tackle. It’s a career goal; it’s not one that can happen overnight. It’s like preparing for a 100-mile century ride. It is a goal that you have to really work on to make it a reality. Of course, a breast cancer vaccine is much more challenging.”
Your research centers on something many never considered possible – a vaccine for breast cancer. Tell us about your work.
The goal of a cancer vaccine is to harness the immune system to fight cancer. Recent studies confirm that the immune system plays an important role in controlling the growth of cancer. Our vaccine targets a protein, mammaglobin-A, that is expressed in almost all breast cancers. The vaccine trains the immune system to find and destroy cells with this protein. If the vaccine proves effective as a cancer treatment, it may someday be used to prevent breast cancer, too.
How long have you been working on this?
I’ve been interested in mammaglobin biology for more than 10 years. My interest predates my recruitment to Washington University in 2005. At the Medical University of South Carolina, where I was previously on the faculty, we were using mammaglobin as a molecular marker for detecting metastatic breast cancer either in the lymph nodes, bone marrow or peripheral blood. It is one of the best molecular markers for the detection of breast cancer.
A main reason why I chose to come back to Washington University – I was a trainee here in general surgery from 1991-99 – was the opportunity to be part of a multidisciplinary team working to develop breast cancer vaccines. We have a very strong immunology community at Washington University School of Medicine, and I’ve been thrilled with the generosity and willingness of investigators here to collaborate. 
Talk about the potential of cancer immunotherapy.
It’s very similar to the story of antibodies for cancer therapy. When antibodies were first identified, the thought was that they’d be the magic bullet. The initial studies with antibody therapy were underwhelming; they were only marginally successful, if that. But we learned a lot in those studies about how and when to use antibody therapies. Now, they’re really a mainstay of modern cancer treatment.
The same is true of immunotherapy. Initially, there was great enthusiasm because of the potential promise, but it’s only because the initial studies were not successful that we were able to learn how to best use immunotherapy. Part of the reason why the enthusiasm has returned is because of the dramatic success of recent immunotherapy trials. 
Give us a broad overview of breast cancer vaccine research.
The vaccine landscape has changed quite a bit. Five years ago, there might have been three to five breast cancer vaccine trials nationwide. Now there probably are 20-plus. There’s a growing realization that, if used appropriately, vaccine therapy can be effective. 
Is the holy grail a vaccine that could prevent cancer in the first place? Is that the ultimate goal of your research?
That’s right. The holy grail would be a vaccine that could prevent the development of cancer. But several steps must be accomplished before we get there. The first is development of a vaccine that’s safe and very effective. Once we have that, we’ll start to use it in early-stage disease or in women who are at high risk for breast cancer and then, ultimately, in healthy women.
I know there’s a lot of frustration that you can’t just move forward to evaluate these vaccines in healthy women, but the reality is, if you’re going to give an investigational treatment to healthy individuals, you have to have enormous confidence that it is safe and effective. There has to be an appropriate balance between the potential risks of an investigational agent and the benefits. 
Switching gears, you’re an active cyclist and a daily bike commuter. How many miles a week do you ride?
I don’t track how many miles or hours I ride, but I ride my bike to work every day. It’s a great way to start and end the day. In the morning, it wakes you up and gets you ready for everything you need to do. And in the evening, it wipes the slate clean so you don’t bring any stress home. I’m very lucky because I have a very pleasant commute. I bike through Forest Park, up and down Wydown Boulevard and through Shaw Park. 
Bike commuters tend to take in more of what’s going on around them. What are some things you’ve seen while riding to and from campus?
I’ve seen all kinds of wild animals. There’s a family of foxes that lives around Wydown Boulevard in Clayton. In Forest Park, there’s a mated pair of owls that has baby owls every year. It’s fun to track their progress. We’re just getting into the season now when you’ll be seeing lots of baby geese. There are all kinds of raccoons and other wild animals in the park. 
Jeanne (top left) and William Gillanders have three children. They are (from left) Teddy, Emma and Ian. “They are very supportive of me and my work, so I’m very, very appreciative of their understanding and patience,” William Gillanders said.
That sounds like a relaxing transition to home. Tell us a little about your life there.
I’m very fortunate to have a fantastic family. My wife, Jeanne, is a teacher, so she sets the tone for the kids and the importance of schoolwork. And we have three kids who are growing up very quickly. My daughter, Emma, is a freshman in high school. Our son Ian is in seventh grade, and our other son, Teddy, is in fifth grade. They’re a lot of fun. They are very supportive of me and my work, so I’m very, very appreciative of their understanding and patience. Whenever I travel I miss home quite a bit. 
Talk about being a physician-scientist. The two are related, of course, but also very different.
I have one foot in the clinical realm and one foot in the research realm. My goal is to bridge those two worlds, to collaborate with all the great basic scientists here at Washington University School of Medicine and help them move their great ideas into the clinic. 
Your father is a physician, too. What medicine did he practice? Was he the inspiration behind what you’re doing today?
Yes, my father is a retired obstetrician-gynecologist, in one of the surgical subspecialties. I remember him talking about surgery when I was younger.
One of the things I’ve enjoyed quite a bit with my father recently is that when he comes to visit he likes to walk. So I set aside my bike and we walk to work together. He’s in his 70s, and he walks fast. That’s really been a great time to bond with him. My father and I have seen some of the wildlife I mentioned earlier. One morning we were visited by a bald eagle that flew right over our heads. It’s an hour-and-45-minute walk, and often as we trek through Forest Park the sun comes up. It’s a great way for my father and me to spend time together. 
Another way you’ve combined your work and personal life is through Pedal the Cause, the annual cycling fundraiser for cancer research at Siteman Cancer Center and St. Louis Children’s Hospital. You’ve received grants from the group; you’re a participant in the bike ride.
I’ve been an avid cyclist for many years, and I remember meeting the founder, Bill Koman, before the first Pedal the Cause in 2010. He was very excited about the event, and I share his passion and enthusiasm. 
I’ve done every Pedal the Cause so far. Initially, I was captain of the Siteman Cancer Center team. Since then, individuals from that original team have gone on to start eight or 10 new teams. These teams are focused on difference cancers, such as breast cancer, pancreas cancer, lymphoma, head and neck cancer, prostate cancer and other cancers. There’s a lot of enthusiasm for Pedal the Cause, and I’ve had a lot of fun doing it. I just wish that the funding decisions would integrate finishing time into the overall algorithm for deciding on who is funded! 
What kind of patients would be helped by your research?
We have two clinical trials in the works. One is already open to patients; the other soon will be. For the open trial, we’re recruiting newly diagnosed patients to study the safety and effectiveness of our mammaglobin-A vaccine. For the other trial​, we will recruit 30 patients. Although it remains to be determined what cancer patients will benefit most from these vaccines, I think there is potential that vaccines ultimately will be used in all stages of the disease.

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