Fellows Feature: Natalie Telis

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Natalie Telis is a CEHG graduate fellow in the lab of Jonathan Pritchard. She is a graduate of the University of California, Davis with bachelors’ degrees in Mathematics and Cell Biology. Her research focuses on the evolutionary connection between human variation and modern disease, with specific work on recent adaptation and the biological consequences of Neanderthal-acquired variants. 

Can you tell us a bit about yourself, personally and professionally? 

I was born in Brooklyn a few months after my mother came here from Russia, and lived there until starting primary school. I’ve been a Californian ever since! I lived in the Bay Area for about 10 years, then completed my undergraduate degrees in Math and Cell Biology at the University of California, Davis and promptly came back here to the Bay for my graduate work. After I defend, I’ll be starting a position as a Statistical Geneticist at AncestryDNA, where I’ll be continuing to dive into human genetics in a very different environment (with a lot more snacks). When not in the lab I like bicycling, drawing and teaching my cats tricks.

Why did you become a scientist? What got you interested in genetics and science?

Growing up in the area, I was a total math nerd, but I was also fascinated with marine biology. This fascination was mostly driven by weekends my mother and I spent hiking in Santa Cruz; the marine fossils we found totally captivated me.

My marine biology interest persuaded my mom to let me keep two fish tanks, and this is what turned me into an evolutionary biologist. We had decorated them a little differently, and accidentally transplanted some brown snails into both tanks alongside some plants. Much to our chagrin, they defied our fish’s constant efforts to eat them all. But over the months, the snail colors changed! Within the year we had one population of light brown snails and one of super dark black snails, just like the gravel at the bottom of my 2 tanks. I couldn’t believe what I was seeing.

I clamored for a genetics textbook, and my mom found this free online educational genetics game where you could breed and genome-edit dragons to probe the heritability of cool dragon traits. I was basically hooked from there. I struggled to resolve my interests in math and genetics until college; then I realized there was no need for me to choose between math and genetics when I could simply do both and be a computational geneticist.

Can you tell us about your current research and what you want to achieve with it?

In my day to day research, I work on connecting the history of genetic variants with their modern effects. We have a lot of reasons, both theoretic and empirical, to believe the history of a variant – like what population it comes from, how long it’s been around and in what environment – has the potential to change how common it is. And obviously with variants that might affect disease, we want to be able to connect this history to explaining some of that modern disease risk.

To that end,I’ve worked on a few projects here. One major one has been detecting signals of evolution’s influence on the architecture of complex traits. As opposed to simple single-gene, single-effect, single-disease traits, these are more like amalgamations of many tiny effects. Traits like this include everything from height and other body measurements to metabolic function or immune response. And picking apart this evolutionary history can suggest how our historic environment is playing a role in shaping the modern prevalence of disease-altering variants.

Another example of work I’ve done has focused on variants from somewhere really different – those that we inherited from Neanderthals when we met them 50,000 years ago. By connecting those variants and their evolution to their modern tissue function, we can start explaining why they might be good or bad for us and what that means about unique human-specific biology.

Connecting this history to the modern day helps us start understanding how these traits, disease or otherwise, really work. And picking apart genetic architecture is fascinating! But these signals are really subtle I get at them day-to-day using mathematical and statistical methods. Coming up with those methods is a big job in and of itself.

Moreover, those methods have broader applications as well, and so I have spent a good amount of time pursuing some of those totally different applications. I’m working actively on a project quantifying gender differences in behavior of scientists in scientific settings, like at conferences or meetings. We’ve taken data for almost 14,000 scientists with 2,000 questions asked between all of them to learn how scientists ask questions and how that connects with their gender. The math is really the same, but the real world relevance is totally different, and that’s something that really excites me.

What are your future plans? Where do you see yourself professionally in the next 5 or 10 years?

I have had an amazing time at Stanford, being a part of the excellent community of geneticists here, and I’m very excited to continue. I think there are a lot of amazing opportunities for incredible research, especially for human geneticists, in industry. There are some incredible datasets out there, and I’ll be really excited to start working with the giant dataset at AncestryDNA, where I’m starting after my defense.

In the next five to ten years, I hope to continue contributing to the space of human genetics, and to keep weaving together human genetic history with the way modern human traits and diseases work. I’m also really excited to have the ongoing opportunity to bring those results to consumers and to evangelize for the incredible value of human genetics and the power it has to connect us with our unseen, unknown history – and maybe even our own futures.

Were there people in particular to whom you would attribute your professional success?

I’ve had the privilege of working with a lot of incredible people on my journey. As an undergraduate at UC Davis, I got to work with Drs. Ian Korf and Simon Chan, the latter of whom passed away shortly before I graduated. They were incredibly candid and supportive with me about the scientific process and did an amazing job training students to really think critically about their work and the work of others. They also helped steer me into computational evolutionary genomics.

I was honestly worried about whether I’d find a lab environment as wonderful as my undergraduate one after I left, but I shouldn’t have been! Working with my advisor, Jonathan Pritchard, and my wonderful labmates has been a huge privilege and the best part of being at Stanford. Jonathan is really focused on thinking critically about stories – not only our own narratives as we work and write, but also about those of others, when we read papers together. He has a really nuanced understanding of what a mentee needs and especially as I finish my graduate work it is so clear to me how much I’ve gained from working with him. He also has a group with lots of shared interests; many of us spend time outside of lab enjoying espressos, hiking, board games or the occasional secret baking contest.

Can you speak a bit to the role you see CEHG playing on Stanford campus?

One challenge about how large Stanford is the broad spread of intellectual wealth – from the Genetics department to the Statistics department, there are people doing fascinating work that I don’t get to connect with in any other way. I feel like CEHG really fills these gaps for me as a student. CEHG’s yearly symposium and the weekly seminars (like EVOLGENOME) bring together that big on-campus community for feedback and discussion. Plus, their access to incredible speakers from outside Stanford has been a major asset – I credit CEHG events with most of my success job-hunting because they connected me with people whose perspectives and networks were a huge benefit to my path.

What advice would you offer to other grad students or postdocs who are considering pursuing a similar educational and career path as you?

I think we are in a really golden moment right now where you can choose to pursue genetics research in a remarkable number of ways. There is a lot going on outside of academia that’s also incredibly rewarding. There are institutes like HHMI’s Janelia Farm or the Hutch that are focused on academic research without teaching; there are positions that mirror professorship like the Sandler Fellowship (or the QB Fellow program at Cold Spring Harbor Labs). And, of course, there is a lot of industry research, ranging from the industry postdoctoral programs to full-blown researcher positions. It’s an amazing time to be a geneticist.

When starting my graduate work, I really lacked an understanding of these opportunities and the nuanced differences between each path. I think starting to understand it and thinking critically about what I wanted to do full-time was crucial to going the direction I did. I would suggest really investigating options and reaching out to people that have gone down different paths to understand what their day-to-day is like, and figure out how that aligns with what you’re hoping for.

Tell me what you do when you aren’t working on research and why. Do you have hobbies? Special talents? Other passions besides science? 

My labmates would definitely say my most notable hobby is art. I illustrate all of my own talks (mostly out of frustration with making bad block-and-circle chromosomes in Keynote) and I was even fortunate enough to win the Genetics Department jacket contest over the summer, meaning one of my art pieces walks around campus most days, and is even prominently visible at most CEHG events. CEHG doesn’t have any art contests, do they? 🙂

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Fellows Feature: Hannah Kim Frank

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Hannah Frank is a CEHG postdoctoral fellow in the laboratory of Scott Boyd. She completed her bachelor’s degree at Harvard University and her PhD at Stanford University in Elizabeth Hadly’s lab where she studied the ecology and evolution of bat-infection interactions, particularly in Costa Rica. Her postdoctoral research focuses on the comparative genomics of the adaptive immune system of non-model organisms, with a particular emphasis on bats.

Can you tell us a bit about yourself, personally and professionally? 

I grew up in Pasadena, CA where I spent most of high school volunteering as a docent at the Los Angeles Zoo before going to Harvard to study Organismic and Evolutionary Biology and catch a lot of Anolis lizards as part of my undergraduate research. After college, I lived in New Zealand for a year on a Fulbright, studying the hematology of a threatened, endemic reptile called a tuatara. They’re the closest relatives to snakes and lizards that’s not a snake or a lizard and they are only found in New Zealand. Look them up! Finally, I came to Stanford where I did my PhD in Elizabeth Hadly’s lab on the ecology and evolution of the relationship between bats and their infections.

I am now a postdoctoral fellow in Scott Boyd’s lab in the pathology department where I am continuing my research on bats with a focus on their adaptive immune systems, as well as expanding my inquiry into other thoroughly non-model organisms. (Capybaras here I come!)

What got you interested in genetics and science? Did you want to be a scientist as a child? 

I have always been a total science nerd generally, but I was always really interested in animals and thought I would be a veterinarian since I was a small child. Both of my grandfathers were physician researchers and, as a kid, I borrowed histology slides from the high school biology teacher to look at under the microscope. In high school, I volunteered as a docent at the Los Angeles Zoo, leading tours and teaching people about the animals, which made me fall in love with ecology and evolution. I also loved molecular biology, but thinking I would eventually be a veterinarian, I focused on ecology and evolution through undergrad and decided to do a postgraduate fellowship studying eco-immunology. In between undergrad and the fellowship, I worked as a veterinary technician. I was very torn about whether to pursue a PhD, a DVM (doctor of veterinary medicine) or both. I actually did not decide between veterinary school and a PhD (or both) until the day my grad school decision was due. At that point I figured that I would work on something that had nothing to do with health and that I’d given up on the medical side of my interests forever. Fortunately, my PhD work and my postdoc work has allowed me to marry my interests pretty nicely. (So to the stressed out students out there – everything works out!)

Can you tell us about your current research and what you want to achieve with it?

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Broadly, I am very interested in how animals’ environment and behavior impact their evolution, in particular as it relates to disease. Bats are a particularly interesting study system for these sorts of questions and for their relationship with people. On the one hand, they are incredibly diverse, both in terms of number of species (1300+ and counting!) and their ecology (only 3 species eat blood; some eat fruit, some bugs and some even fish). This makes them very important for ecosystem function (e.g. pollination, pest control, seed dispersal) and targets of conservation. On the other hand, they are also the reservoirs of a number of viruses that are highly lethal to humans but that do not seem to adversely affect the bats (e.g. Marburg fever, rabies, SARS, Hendra virus, Nipah virus).

Therefore, understanding how all of this ecological diversity translates to differences in infections and species’ responses to their pathogens can help us protect bats, humans and the environment.

In my PhD, I focused on the ecological aspects of this relationship (as well as understanding how humans mediate disease risk for the bats and themselves). I also started a project examining genomic positive selection in response to pathogens in bats globally, linking my ecological studies to evolutionary time scales via genomics. I am continuing this line of inquiry, trying to understand which genes are under selection in which lineages and linking those differences with host biogeography and pathogen identity. I am also delving into the adaptive immune system which helps the body recognize specific pathogens and derives its diversity from gene rearrangements and somatic mutation, making it hard to study from germline sequences. I hope to learn more about how bats recognize and fight pathogens so we can help both bats and humans.

What are your future plans? Where do you see yourself professionally in the next 5 or 10 years?

I really enjoy university settings – doing research, teaching and mentoring others and finding out new and interesting things about the world. I hope to one day be running my own lab, likely focused on investigating host adaptation to pathogens. When I started my PhD on bats, I was pretty sure it would be a temporary thing, but they have grown on me, so perhaps in 5-10 years, I will still be working with them. (Who doesn’t love working with highly intelligent, slow growing, nocturnal, flying, potentially rabid study organisms?) I might need to pick something a little more experimentally tractable too though.

Were there people (or one person) in particular to whom you would attribute your professional success?

I have been fortunate to have had a number of amazing mentors who have helped get me to where I am now. My undergraduate advisor, Jonathan Losos, was the person who helped me realize that I might want to pursue research as a career and has remained a really supportive mentor even as I enter my postdoc. I was also amazingly lucky to have benefited from the guidance and encouragement of Farish Jenkins Jr., my vertebrate anatomy professor. He passed away my first year in grad school, but he was a big part of why I did a PhD. My advisors in New Zealand, Nicola Nelson and Anne LaFlamme, really helped clarify to me that I could unite my disparate interests and gave me the opportunity to do a project that I’d conceived of myself. Finally, my PhD advisor, Elizabeth Hadly, is the reason I’ve grown into the independent scientist I have. She really encouraged me to pursue my interests, connect with others from disparate disciplines and figure things out which gave me the confidence to do just those things.

I had the benefit of getting to know Scott, my postdoctoral advisor, a few years ago as a member of my PhD committee, and I have been Boyd lab-adjacent for a couple of years. It has been really fun joining the lab – everyone is excited and helpful and they think about such different things than I do. Going from an ecology and evolution focused program to the pathology department has been fun and challenging. I’ve learned so much about immunology and the analyses that can be performed in well studied systems like humans and mice. I’d like to think I am also teaching my lab mates as well – I took Scott to catch bats and he said it was the first time he had ever done science outside!

What advice would you offer to other grad students or postdocs who are considering pursuing a similar educational and career path as you? 

  • Being a graduate student/ postdoc/ scientist can be the best job in the world and it can make you want to tear your hair out. Try not to lose sight of why you were excited in the first place and, if that does not excite you anymore, try and figure out what does. It’ll make it that much easier to deal with your nth experimental failure, the server that just crashed, or the realization that a little error you made two months ago means much of what you’ve done since is unusable.
  • Don’t be afraid to explore and get creative. Talk to people who do different things from you; approach people at conferences who aren’t in your subfield. You never know what interesting ideas you might get! (Or in my case, a husband – we met at the International Bat Research Conference. Yes, my family calls him “Batman.”) If you can’t find someone in your lab/ department/ school that’s doing what you want to do, don’t be afraid to reach out to people further afield.
  • Learn how to code. It’s incredibly useful and surprisingly fun. (And I imagine much easier and less stressful to do if you’re not simultaneously trying to analyze data for a deadline.)

Can you speak a bit to the role you see CEHG playing on Stanford campus?

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Hannah (right) at the 2016 CEHG Symposium. Image courtesy of Saul Bromberger & Sandra Hoover Photography

CEHG was really valuable to me during my PhD, helping me learn from people in really different but complementary disciplines to my own. I found an important collaborator on my work through attending his Evolgenome seminar and I always learn a ton from the CEHG symposium. My work is really interdisciplinary – I’m an evolutionary ecologist in a pathology department – and I really value the focus CEHG has on facilitating conversations and collaborations between people with different skill sets and expertise. In my current projects, I am working with evolutionary computational biologists, hematopathologists, conservation organizations and everyone in between; those sorts of inquiries can only happen when people are willing and excited to work on something new.

Tell us what you do when you aren’t working on research and why. Do you have hobbies? Special talents? Other passions besides science?

For most of last year, when I wasn’t working on finishing my dissertation, my “hobby” was wedding planning. With that over, I have enjoyed getting back to baking, hiking and hanging out with friends and my 6 frogs, betta fish and bearded dragon.

 

Fellows Feature: Chuan Li

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Chuan Li is a CEHG Postdoctoral fellow in Dmitri Petrov’s Lab. She received her Ph.D. in Ecology and Evolutionary Biology with a dual degree in Statistics from the University of Michigan in 2017.  Her research includes epistasis and speciation. In the Petrov lab, she studies the interaction between protein interfaces and antagonistic pleiotropy.

Can you tell us a bit about yourself, personally and professionally? 

Born in a small village where my family runs a farm, I have been obsessed with observing the fabulous natural world, which attracts me to the field of biology. I love growing plants. I am also interested in linguistics. I speak multiple languages and enjoy communicating with people from different cultural backgrounds.

I received my Ph.D. in Ecology and Evolutionary Biology with a dual degree in Statistics at the University of Michigan in 2017. During my Ph.D., I worked in quantifying intergenic and intragenic epistasis at a large scale using both experimental and computational approaches with yeast as the model system. I have multiple publications on intergenic and intragenic epistasis, including a Science paper on the empirical determination of the fitness landscape and epistasis of a tRNA gene.

How did you first become interested in genetics and science? Did you always want to be a scientist?

I have loved to explore the wild and read books about biology since I was a child. Very naturally, I chose biology as my undergraduate major. Initially, I was interested in ecology and ecosystems. However, in my junior year, I read a book named Recombinant DNA: Genes and Genomes by Dr. Watson and another one named Evolution by Dr. Futuyma. I became fascinated by evolution and genetics. After having an internship in the Beijing Genomics Institute, I decided to pursue a career to study evolution from a genetics perspective.

After completing my undergraduate study, I started my Ph.D. at the University of Michigan and spent years studying yeast genetics and genomics, focusing on speciation, fitness landscape and epistasis. During my Ph.D., I have been following up on publications by Dr. Petrov’s group. I am particularly interested in their work on quantifying fast adaptation, and high-resolution lineage tracking by Bar-seq to reveal evolutionary dynamics. I met Dr. Petrov in person at a genetics conference (TAGC), where he was the coordinator for a section where I gave a presentation. Later after my PhD, I decided to come to his lab for postdoctoral research.

Can you tell us about your current research and what you want to achieve with it? 

My general research interest lies in studying epistasis, which means interaction within and between molecules. The term has been widely used to describe a broad range of complex interactions among genetic loci, including the functional relationship between genes, the genetic ordering of regulatory pathways, the quantitative differences of allele-specific effects, etc.

Epistasis is a prevailing phenomenon, and the phenotypic effect of a mutation can depend on its genomic background and the potential interaction with other genes or sites. Quantifying such interaction has important theoretical and real-life applications, including understanding evolutionary trajectories, quantitative traits and complex diseases.

My current research in Dr. Petrov’s lab focuses on studying the mechanisms of cancer progression and metastasis. Cancer progression can be viewed as a fast evolutionary process, with lots of mutation happening in a short period, where epistasis would play an important role. The research is in collaboration with Dr. Monte Winslow’s Lab.

Using a technique called ultra-deep barcode sequencing (Tuba-seq), we can uncover enormous tumor growth variability and unveil the underlying genetic mechanisms. This technique uses lentiviral vectors to modulate expression of candidate genes and uses barcode sequencing to precisely measure the size of millions of DNA-barcoded tumors. Such a technique allows for quantifying the relative contribution of each tumor suppressor and their combinations, as well as responses to different treatments and treatment combinations, which can be viewed as genotype-by-genotype and genotype-by-environment interaction. Gaining such insight will greatly benefit clinical treatment for patients with various genetic backgrounds, helping to choose the correct therapy and avoid using unfruitful therapies, ultimately achieving personalized medicine.

What are your future plans? Where do you see yourself professionally in the next 5 or 10 years?

Over the course of my postdoctoral research, my goal is to understand the various underlying mechanisms of epistasis, which would greatly benefit the understanding of many complex traits, and contribute significantly to the area of synthetic biology. Through conducting research, I plan to enhance my capabilities in statistical modeling and experimental design, and hone my skills in both computational and experimental research. Enjoying the collaborative environment in Dr. Petrov’s lab and having access to substantial resources of the Stanford community, I hope my interdisciplinary background in statistics, programming and biology will substantially contribute to the completion of interesting projects.

In the next 5 to 10 years, I wish to establish my lab and keep working on fascinating cutting-edge topics with outstanding collaborators. Meanwhile, I am also looking forward to spreading relevant knowledge to the community.

Were there people in particular to whom you would attribute your professional success?

Yes, I think several people have greatly contributed to my professional success. My family has been very supportive of every decision I make. My undergraduate advisor and my Ph.D. advisor have been of enormous influence, both being a role model in conducting scientific research and training me scientifically. Moreover, my best friend from high school has been very helpful, because she kept telling me that studying biology would fit me very well, which I think had an impact on me.

Throughout my Ph.D. study, I worked on projects independently, with advice mostly from my mentor. It has been very helpful for independent research training, where I get to do every detail including asking the scientific question, conducting experimental work, analyzing the collected data and drafting a manuscript. But collaboration is very important, too.

After starting my postdoc at Stanford, I love the atmosphere of collaboration. I just started my first project here, and have benefited a lot from the discussion with multiple professors when designing my project. By taking advantage of the expertise of multiple groups, it becomes much faster to complete a project in a better way.

Can you speak a bit to the role you see CEHG playing on Stanford campus?

CEHG has been the interdisciplinary hub of Stanford genomic research from multiple perspectives, with interdisciplinary research and collaboration being the core value. Having such hubs are vital nowadays as biology research has become more interdisciplinary. My work in collaboration with Dr. Winslow’s lab embodies such values, where people from different backgrounds work together to understand cancer evolution better, and such effort couldn’t be easily completed by any individual.

What advice would you offer to other grad students or postdocs who are considering pursuing a similar (educational and career) path as you?

It would be of great importance for students to gain some knowledge or experiences in both wet and dry lab, which expands our horizons and helps us to communicate with other scientists. Also, learning some basic statistics would be of great help, and there are many wonderful on-campus and online resources for doing that. Completing a formal dual degree is another option, too.

Tell us what you do when you aren’t working on research and why. Do you have hobbies or special talents? 

I love translation and doing sports. I have been doing technical translation in English, Chinese and Japanese and also serving as a volunteer translator for the community center for years. My favorite sports include tennis, table tennis and Taekwondo.

 

Symposium Report: Stanford One Health Focus on Comparative Oncology

Event Details:

Stanford One Health 2017: Focus on Comparative Oncology

May 8, 2017

Frances C. Arrillaga Alumni Center


Report prepared by:

Ashley Zehnder, DVM, PhD, ABVP (Avian)

Stanford Department of Biomedical Data Science

Co-Director, Stanford One Health

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Report Contents:

  1. Mission/Goals
  2. Meeting format
  3. Conference speakers with bios
  4. Demographics of attendees
  5. Potential new collaborations
  6. Conference evaluations
  7. Future plans

Mission/Goals:

The purpose of Stanford One Health: Focus on Comparative Oncology was to connect Stanford clinicians and researchers to cutting-edge comparative research and resources in order to aid the translation of basic science cancer discoveries to the clinic.

We expected that this focused symposium would produce:

  • New collaborations and novel hypotheses for investigations around translational cancer research.
  • Potential for new approaches to the diagnosis and treatment of disease in both animals and humans.

This conference emerged as a continuation of other Stanford One Health symposia, held in 2014 (http://med.stanford.edu/compmed/zoobiquity.html) and 2016 (http://med.stanford.edu/compmed/one-health-2016.html), that focused on a broad range of topics. The main organizers of SOH 2017 were Ashley Zehnder, DVM, PhD, DABVP(Avian), a research scientist in the Department of Biomedical Data Science with a focus on comparative oncology research, and Donna Bouley, DVM, PhD, DACVP, and Jose Vilches-Moure, DVM, PhD, DACVP, pathologists in the Stanford Comparative Medicine Department.

Meeting Format:

The symposium began at 9:00 AM and concluded at 3:30 PM. We opened with an introduction by organizer Ashley Zehnder and Dr. Carlos Bustamante, Inaugural Chair of the Department of Biomedical Data Science. The morning session consisted of four veterinary oncology speakers, highlighting different translational cancer programs from around the country, including Colorado State University, the University of California, Davis, the University of Minnesota, and the NIH Comparative Oncology Trials Consortium.

The afternoon session consisted of a focused discussion panel on four topics:

  1. Areas of collaboration between Stanford and the comparative oncology community;
  2. Ways in which a more collaborative approach to translational research can help Stanford researchers develop novel therapies;
  3. Potential funding sources for collaborative research projects;
  4. Ways to engage Stanford trainees (MD, PhD, postdocs) in comparative oncology.

[Discussion transcripts and whiteboard notes pending]

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SOH2017 Attendees

Speakers and Bios:

Rodney Page, Professor and Director of the Flint Animal Cancer Center, Stephen Withrow Presidential Chair in Oncology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University

Dr. Page received his DVM from Colorado State University and completed specialty training in the field of medical oncology in NYC.  He was a faculty member at North Carolina State University, prior to his appointment at Cornell University as Founding Director of The Sprecher Institute for Comparative Cancer Research. In 2005, Dr. Page was appointed Chair of the Department of Clinical SciencesDr. Page returned to Colorado as the Director of the Flint Animal Cancer Center in 2010 (www.csuanimalcancercenter.org).  His research interests have recently been focused on a ‘One Medicine’ approach to cancer. He has been involved with the Golden Retriever Lifetime Study since 2008, and has initiated a national effort to bring translational and comparative oncology to a greater audience. Website 

Antonella Borgatti, Associate Professor, Department of Veterinary Clinical Sciences, University of Minnosota

Dr. Borgatti graduated cum laude from the University of Torino, Italy in 1996. After three years in general practice, she received a scholarship to pursue specialized training in oncology at North Carolina State University, where she subsequently remained as a Research Associate, Oncology Intern, and Clinical Instructor in Oncology. She completed a Residency in Comparative Oncology at Purdue University, where she also received a Master of Sciences Degree in 2006. Dr. Borgatti became a Diplomate of the American College of Veterinary Internal Medicine (Oncology) in 2006, and a Diplomate of the European College of Veterinary Internal Medicine in 2007. She worked at a specialty referral hospital in North Carolina for two years before joining the faculty at the University of Minnesota in 2008. She is currently Associate Professor of Oncology in the College of Veterinary Medicine, Member of the Masonic Cancer Center, Member of the Vallera laboratory, and Director of the Oncology residency program. Website

Michael Kent, Director of the Center for Companion Animal Health, UC Davis

Michael Kent is a Professor of Radiation Oncology at the University of California, Davis’s School of Veterinary Medicine. He is also Director of the Center for Companion Animal Health. He graduated from veterinary school at UC Davis in 1997. He then went on to do an internship at the University of Pennsylvania. This was followed by a year in private practice in Pennsylvania before he went on to do residencies in Medical and Radiation Oncology at UC Davis, where he also received his Masters Degree in clinical research. He is also the program co-leader for the comparative oncology program at the medical school’s NCI-designated comprehensive cancer center. His research interests include clinical trials and tumor biology of canine melanoma and osteosarcoma. Website

Amy LeBlanc, Director, Comparative Oncology Program, NIH

Dr. LeBlanc is a board-certified veterinary oncologist and Director of the CCR Comparative Oncology Program at the NIH’s National Cancer Institute. In this position, she directly oversees and manages the operations of the Comparative Oncology Trials Consortium (COTC), which designs and executes clinical trials of new cancer therapies in tumor-bearing pet dogs. Her research focuses on animal modeling for the development of new cancer drugs and imaging agents, and identification of imaging biomarkers, development, and optimization of PET imaging hardware and imaging protocols. She has experience in fostering collaborations with industry and academic partners to support relevant eIND studies in man. She has given numerous invited lectures on the inclusion of companion animals in imaging-based translational research, and the value of comparative oncology in drug and imaging agent development. Website

Demographics of attendees (Including speakers and organizers):

Conference attendance was capped at 45 to allow for more active discussion and interactions between speakers and participants. There were 44 pre-registered attendees and a total of 32 final attendees.

Degree Total % Total
DVM 2
DVM/MD 1
DVM/Board Certification 9
DVM/PhD 1
DVM/PhD/Board 3
Total DVM 16 48.5%
MD 1
MD /PhD 3
Total MD 4 12.5%
PhD/PhD Cand 6 18.8%
Other (NP) 1 3.1%
Not Stated 5 15.6%
Total 32 100.0%

New collaborations from the meeting:

Collaborator1 Institution1 Collaborator2 Institution2 Project/topic
Bryan Smith Stanford Michael Kent UC Davis Molecular imaging
Ashley Zehnder Stanford Michael Kent UC Davis Veterinary data science
Kevin Grimes Stanford Antonella Borgatti UMN Cancer drug translation
Teresa Purzner Stanford Michael Kent UC Davis Osteosarcoma
Jianghong Rao Stanford Amy Leblanc NIH NCI PET imaging agents
Juergen Willmann Stanford Amy Leblanc NIH NCI Molecular imaging
Carlos Bustamante Stanford Rod Page CSU Bioinformatics training program

Several new collaborations are being explored following this meeting between the invited speakers and researchers at Stanford, including research focused on molecular imaging, veterinary data science and bioinformatics, cancer drug translation and osteosarcoma research.

Evaluations (quantified results pending): 

Conference feedback was all very favorable, especially regarding the symposium content and speakers. Everyone from Stanford who has provided feedback, thus far, has supported the development of a formal One Health program at Stanford.

Future Plans: 

We are very pleased with the success of all three “One Health”-themed conferences (the Stanford Zoobiquity Research Symposium 2014, One Health 2016, and the 2017 focused symposium on Comparative Oncology). The Stanford One Health Advisory board is currently working on a proposal for a formal One Health Center for the University’s long-range planning process.

 

 

Feature Interview: Dr. Plavi Mittal, Founder & CEO, In-Depth Genomics

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Dr. Plavi Mittal earned her Ph.D. in Biology from Brandeis University, and did her postdoctoral research in molecular oncology at Harvard Medical School. She was also a management consultant at a global consulting firm, where she worked with leading pharmaceutical companies.

After a family member was diagnosed with a rare muscular dystrophy, LGMD2B/Miyoshi, Dr. Mittal helped create the Jain Foundation. Over the last 12 years, she has led the JF team as President & CEO, and together, they partnered with dysferlinopathy researchers to realize gene therapy clinical trials and the hope for a cure. Repeatedly, Dr. Mittal has seen patients with rare disease struggle to reach a diagnosis and find a treatment best for them, despite the scientific breakthroughs advancing therapies for their condition.

Through her new non-profit organization based in Seattle, Washington, In-Depth Genomics [www.indepthgenomics.com], Dr. Mittal will continue to support the mission of the Jain Foundation while addressing this larger patient need by providing genome-level sequencing and analysis. IDG’s national diagnostic program is an unprecedented effort that will raise standards for diagnosing rare diseases and also fuel a research consortium focused on improving clinical care.

You can follow IDG on LinkedIn and twitter

Can you tell us more about your background before starting the Jain Foundation? How did you first become interested in science, biology, and oncology?

I was always interested in Genetics and Biology for as far back as I remember. I think my interest started when I read the book, Lives of a Cell by Lewis Thomas. I was fascinated with the diversity, the resilience and the complexity of biological organisms. Later, as a PhD student, I was very keen to work on problems that would impact people suffering from diseases today. I feel that we have an urgent mission to connect the dots from everything we have already learned.

Can you tell us about your work at the Jain Foundation over the past decade, and how that led you to start In-Depth Genomics (IDG)? 

At the Jain Foundation, we were completely focused on pushing research towards a cure for LGMD2B, a rare form of muscular dystrophy. Over the years, our strategy of uniting researchers with the relevant expertise proved successful, and we set the stage for clinical trials. Then, I learned first-hand what industry has been struggling with for years: rare diseases are difficult to research, because the patients needed for clinical trials are very difficult to find. With the hopes of finding enough patients to develop a meaningful trial for LGMD2B, the Jain Foundation developed a free diagnostic program. We put together a panel of 35 genes linked with diseases that would have a similar presentation as our disease of interest, LGMD2B. We were able to screen 2,500 people and diagnose dozens of LGMD2B patients. This work confirmed my belief that genetic testing is a quick and efficient clinical tool for complex diagnostic cases.

What convinced you that there is a need for better diagnostics for rare diseases? Why is diagnosis so important for these patients?

While the diagnostic program was very successful at finding LGMD2B patients for the Jain Foundation patient registries, over 60% of the patients tested received no diagnosis. I felt a personal dedication to these patients who were offered the hope of an answer, only to be let down by the inherent limitations of a panel-based approach. These patients would have to wait many more months while they sought other opportunities for genetic testing, if they had the resources to do so. Given the falling price of human genome sequencing and clinical analysis, performing one thorough analysis seemed to me to be more efficient and effective than repeated genotyping. By focusing on providing comprehensive genetic analysis to these patients, I have the opportunity to provide an under-utilized, powerful diagnostic tool to patients in critical need of targeted treatment plans. And by empowering patients with their genetic diagnosis, patients can seek out research and clinical trials best suited to their condition.

How did you choose whole genome sequencing, and how does this open up new avenues for research?

By performing whole genome sequencing, we will be assessing as much of the human genome as technology currently allows. This means that, in addition to identifying known pathogenic variants for diagnostic purposes, we will be able to uncover nuanced patterns in other regions of the genome. We hope that, by strategically combining our bioinformatic analysis with information about patients’ symptoms and traits, we can highlight promising avenues for therapy development for a great number of rare neurological diseases.

What do you think distinguishes IDG from other genetic testing/analysis/diagnosis services available today? Why do you think now is the right time for IDG to open its doors?

I’ve been considering this very question for months – right now, the clinical and academic applications of genomics are booming. So many groups and companies are launching large projects or consumer products that the market appears saturated with personalized technology. However, as I’ve built IDG’s program, it has become painfully clear that the vast majority of commercial products are not able to offer a clinical diagnosis to patients seeking one, or they do not perform a full genome analysis at all. Many insurance plans do not cover comprehensive genetic testing, and patients cannot afford to pay out of pocket for this additional test when they are facing a myriad of diagnostic procedures. By offering our services to patients at no charge, and performing full genome sequencing/analysis for clinical and research applications, we are the only program working to deliver this cutting edge technology directly to patients who could benefit most.

What is your vision for In-Depth Genomics going forward?

 

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My vision is for In-Depth Genomics to become a leader in rare disease diagnosis and patient engagement. By gathering evidence supporting the efficiency of genetic screening for difficult-to-diagnose neurological conditions, I hope to influence a shift in clinical standards of practice. I don’t plan to measure the success of my program only by the number of patients diagnosed; my success is also contingent on creating an accessible community where patients can learn about the unique ways patient participation can accelerate and influence the development of rare disease therapies. By empowering patients and generating sufficient data, I hope IDG’s program will spark therapy development for a number of rare conditions.

What directions do you see genomic testing (including analysis, diagnosis, and counseling) taking in the future? Do you see a lot of change happening in this area? Do you think these changes are positive or negative? Why?

I think we are rapidly moving to the era of unlocking all of DNA’s mysteries, and really charging forward and diagnosing most conditions in much less time. I am not as sure that we, as a species, will take care to provide adequate support, guidance and counseling along with the diagnosis. I hope we do, and IDG is definitely striving for that deep level of engagement with the patient, becoming a source of support for them.

The changes unlocking of the DNA will bring to diagnosis is a big step forward in the right direction. Everything starts with diagnosis: by naming the suffering – then we can begin to understand the origins and begin to develop treatments.

How can members of the CEHG community get involved with In-Depth Genomics?

Once sufficient data is collected, IDG hopes to launch a major research effort that will combine groups across academia and industry who are studying human disease, developing therapies, or performing other computational biology projects that may benefit from data such as ours. Any researcher from the CEHG community who is interested in working with IDG’s curated database should contact the foundation for application.

CEHG’s core values are “collaboration” and “interdisciplinarity.” Are there ways you hope IDG will embody these values as well?

Absolutely! While genomic data is at the heart of this program, I know that progress in clinical care for rare diseases will only occur after combining data from numerous other health factors and biological perspectives. To put our program’s data to the best use, we must rely on collaborations with groups across industry and academia to elaborate on relevant findings and push the genetic information towards a meaningful application.

What advice would you give to early career scientists, having worked in both academia and at foundations with a patient-centric focus?

My advice is to always look 10 steps ahead and find the connection to how your research will help humans. This exercise makes everything so much more focused, and also very meaningful.

What advice would you give to patients?

Advocate for yourself; there are answers your doctor may not know. Participate in all aspects of drug development. Read and get educated about your disease.

Fellows Feature: Ryan York

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Ryan York is a CEHG graduate fellow in the labs of Russell Fernald and Hunter Fraser. He is a graduate of the University of California at Los Angeles. His research is focused on the evolutionary genomic basis of brain and behavior, with a specific interest in the courtship behaviors of Lake Malawi cichlid fish.

Can you tell us a bit about yourself, personally and professionally?

I am a graduate student in the labs of Russell Fernald and Hunter Fraser. I grew up in the Bay Area, and did my undergrad at UCLA. Before coming to Stanford, I worked as a research technician, first in Stephanie White’s lab at UCLA, studying the molecular bases of bird song, and then with John Allman at Caltech, researching neural traits unique to humans. My research is broadly concerned with understanding the evolution of brains and behaviors across disciplines, from genes to organisms. I am also a musician and artist and am interested in the intersections of art and biology.

Did you always want to be a scientist? What initially got you interested in science and genetics?

I didn’t always want to be a scientist. I was not someone who, as a child, knew they were destined to study a specific species or natural phenomenon. In fact, I began my undergraduate years as a Jazz Studies Major, having semi-professionally performed and recorded as a double bassist since the age of 14. What’s more, in high school, I was a “bad” science student, constantly feeling like I couldn’t measure up to those in my class who seemed to show natural talent for understanding and memorizing facts about enzymatic reactions and taxonomy. I was interested, but disengaged, convinced that my future lay in the Arts. Yet when I began taking classes in history and sociology in college, I realized that a whole world of interest existed for me outside of art. I caught the bug of wanting to understand human behavior, and that drive led me to crave more and more fundamental levels of understanding. Sociology led me to psychology, psychology led me to neuroscience, and neuroscience led me to genetics and molecular biology, and ultimately to where I am now.

Can you tell us about your current research and what you want to achieve with it?

My current research is focused on investigating how genomes produce the great behavioral diversity observed in animals. Despite decades of research, we still don’t fully understand how variation in genes and their regulation changes the function of the brain and its main output, behavior (especially our own). Historically, this has been due to technological constraints that incentivized researchers to focus on just a few model systems and behavioral types. Recent innovations in sequencing, neurobiology, and behavioral analysis are now allowing behavioral biologists to expand their focus to new species and groups displaying extreme behavioral diversity. My work attempts to develop methods that integrate these new approaches in order to understand how behaviors evolve and vary across biological levels.

I am primarily focused on an extremely diverse group of fish (cichlids) from Lake Malawi in East Africa. Though Lake Malawi is only around 5 million years old (i.e. very young, geologically speaking), there are already over 800 species of Malawi cichlids. Over 100 of these species perform a mating behavior, called “bower building,” that I am particularly interested in. During breeding season, males of these species will competitively build 3D structures out of sand to attract females, either in the form of a classic “sand castle” or as an excavated depression we a call a “pit”. We have shown that whether or not a male builds a castle or a pit is species-specific and innate, and that if you hybridize a pit species and castle species, the resulting hybrids will build both structures, resulting in a “pit-castle” bower.

To understand the genetic basis of this behavior, I am combining whole genome sequencing and RNA-seq in the hybrids, to uncover variants affecting the regulation of neural genes during different behavioral states. I am also using high-throughput behavioral phenotyping and genetic methods for analyzing signatures of recent neural activity to understand how variation in the cichlid genome leads to different behavioral and neural traits. I am now also working on applying these genetic methods to other types of data and species, including deer mice and fruit flies.

Were there specific people to whom you would attribute your academic and professional success?

There have been various people in my life who have had substantial impacts on my path (though not necessarily in ways that would lead one to predict that I’d end up in science). First off, my family has always been very supportive of whatever I wanted to pursue, be it jazz or evolutionary genetics, and have, at least, attempted to always show real interest in the odd topics I get obsessed with. In high school, my bass teacher, Seward McCain, supported my desire to major in music in college, but also strongly advocated for getting a full education outside of music, in order to avoid being one dimensional.

Multiple people in the sociology and anthropology departments at UCLA – Andrew Deener, Doug Hollan, Zsuzsa Berend, Jeffrey Prager, Alan Fisk – were instrumental in helping me figure out my life outside of music, and how to productively pursue my academic interests. Stephanie White charitably brought me into a real neuroscience lab as a research assistant when I, on paper, had no business being there. John Allman took my ideas seriously and guided me, with expert care, toward the better ones and away from the bad ones.

I have had a great experience working with my graduate advisors, Russ Fernald and Hunter Fraser. Both are wonderful advocates, collaborators, and mentors, and both have made possible whatever success I’ve achieved at Stanford.

Can you speak a bit to the role you see CEHG playing on Stanford campus?

I have found that CEHG provides a home for researchers who may be considered outliers or misfits in their own fields, be it due to their interdisciplinary focus or constant concern for achieving the next big thing (rather than what is currently fashionable). CEHG allows scientists to pursue these ideas at all levels – graduate, postdoc, faculty – knowing that they are supported both institutionally and intellectually.

As both a CEHG fellowship and research grant recipient, this has been really important for my growth as a researcher, and has allowed me to collect data and, in turn, produce work that is much more interdisciplinary and wide reaching than would have otherwise been possible.

What are your future plans? Where do you see yourself professionally in the next 5 or 10 years?

I am very excited to keep helping pioneer the study of behavioral evolution within the biological sciences. There is currently a small, but very motivated community of researchers who are working on ways to tackle this problem, and I would very much like to play a role in expanding this field’s focus and participation. To that end, I’m starting a postdoc this Fall in Tom Clandinin’s lab, to work on fundamental issues in the behavioral evolution of fruit fly species, and develop tools and methods that can be applied to a variety of species. In the future, I’d like to have my own lab, teach, and advocate for the benefit of using evolutionary perspectives in neuroscience, psychiatry, and human genetics.

What advice would you offer to other grad students or postdocs who are considering pursuing a similar educational and career path as you?

GET INTERESTED. It’s true that science is difficult, and to do it well requires knowledge of, and training in, an array of topics. But, in my experience, one of the main determinants of whether or not someone sticks with, and is successful in, science is their level of engagement with their topic.

Research benefits from an almost obsessive focus. Deeply wanting to know the answers to your questions somewhat forces the attainment of needed skills and knowledge. To me, this should be the way a researcher progresses, in the service of a project or question they are interested in, rather than in the service of the requirements of a graduate program or CV.

Tell us what you do when you aren’t working on research and why. Do you have hobbies? Special talents? Other passions besides science? 

I still compose, record, and perform music, though the amount depends on where my research is at any given moment. These days, I am increasingly interested in working on ways to integrate science and art, both in the production of my music and visual art, and in the way my scientific work is displayed and disseminated. I also rock climb quite a bit and am, as of recently, an extremely amateur dumpling maker.