Fellows Feature: Karthik Jagadeesh

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Karthik Jagadeesh is a CS Ph.D. student in the Bejerano Lab. He has a B.S. in EECS and B.A. in Applied Mathematics from UC Berkeley. He is building statistical models to identify disease causing mutations and computational tools to improve rare disease diagnosis.

Let’s start by having you to tell us a bit about yourself, personally and professionally. 

I am a Computer Science PhD student in Gill Bejerano’s research group. My research is focused on studying the human genome to build computational tools and statistical methods to better interpret patient’s genomes and diagnose Mendelian diseases. Prior to joining Stanford, I did not have much exposure to computational biology, but I fell in love with genomics after joining the Bejerano Lab and seeing how we can extract meaning from genomic code. I completed my undergraduate degree from UC Berkeley in EECS and Applied Math, where I had brief research stints in databases and computer security and completed an honors thesis exploring approximation algorithms in Applied Mathematics.

I grew up 20 minutes south of Stanford in Saratoga, CA and am a Bay Area native. I enjoy playing tennis, hiking, and traveling in my free time.

Why did you become a scientist? Did you want to be a scientist as a child?

I spent my childhood at the center of the internet technology revolution in Silicon Valley. Growing up in this environment, I was impressed by the impact people here had on the local community and the world. I soon realized that fundamental research in science and technology is what allows this impact to be possible. Starting in undergrad, I explored various research topics and was particularly excited by data and applied machine learning problems. After coming to Stanford, I found that computational tools have the ability to transform our understanding of the human genome. From the compilation of my undergrad research and work experiences, I have refined my interest in computational genomics and specifically human disease genomics.

Can you tell us about your current research and what you hope to achieve with it? You could start by listing 3 words you think best represent or embody your research.

Mendelian disease diagnosis.

My research goal is to bridge the gap between genotype and phenotype, and understand the ways in which genetic variation contributes to phenotypic diversity and ultimately human disease. Mendelian diseases are diseases that are caused by mutations to a single gene. As typical individuals have around 4 million variants genome wide, we aim to develop computational techniques to find that “needle in the haystack”. Using data from next-generation sequencing and tools from computational biology and machine learning, I have worked on projects ranging from machine learning for variant pathogenicity prediction to cryptographic techniques for genome privacy.

M-CAP, a machine learning classifier, reduces the variants of uncertain significance in patient genomes by 60% while maintaining high sensitivity, and has become widely incorporated into exome analysis projects and pipelines. The scores are available through the popular ANNOVAR tool as well as through dbNSFP. Additionally, thousands of users have downloaded our VCF file of exome wide scores and hundreds of users query our online web search tool every day.

Another recently published project on genome privacy introduces a secure framework to compute flexible functions over genomes from multiple individuals while preserving patient’s genomic privacy. Genome privacy is becoming more important, especially as we start to understand more about the genome and how it encodes function. It is critical to build secure methods for genomic analysis as this allows individuals to continue to share their genomes while maintaining anonymity.

Recent Press on genome privacy:

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

There are many people that have helped me get to where I am and for whom I am deeply grateful, including my family, my lab mates and especially my mentor Aaron Wenger and my advisor Gill Bejerano.

Aaron taught me a lot about genomics, specifically in the context of disease, and he helped me frame my first project, and structure a concrete approach to tackle it. I have continued to employ a lot of these strategies I learned from him on projects I worked on later. Aaron and Harendra Guturu (another one of my mentors) both built many of the computational tools and data processing pipelines that are a foundation of the medical genetics work I have done.

Gill gave me an opportunity to join his lab though I came with no background in biology. One of my favorite parts about working with him is the interesting discussions and brainstorming sessions that we have. He constantly pushes me to think deeply about my research and asks questions, forcing me to have a thorough understanding of the underlying methods. Gill also has a detail-oriented approach to research, writing, and presenting which has taught me not only how to approach research but to also package and present my work so it can be understood by multiple audiences.

Research is a truly collaborative process and working with the members of the Bejerano lab and seeing how ideas and tools have been passed down and improved generation by generation has really influenced my experience as a PhD student.

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

I am planning to graduate in the summer and am currently applying to postdocs. I hope to continue improving our understanding of the genetic basis of diseases, specifically through expanding interpretability of the noncoding genome and complex diseases. Eventually, I hope to become a PI with a lab focused on developing computational methods to improve the understanding of the genetic architectures of human disease.

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

CEHG is awesome! CEHG organizes many interesting talks and lectures throughout the year, such as the CEHG symposium, and these events provide a great opportunity to learn about new topics as well as meet other people working on related topics.

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

In general, I feel there are a lot of interesting opportunities at the intersection of fields. As a young scientist, it is good to spend time developing a strong foundation and skills in two diverse areas. This allows you to have the expertise to build novel solutions to problems by connecting ideas from different areas – something not many can do.

 

 

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Bridging cultural gaps: scholars promote interdisciplinary studies in human cultural evolution

Within the blink of an eye on a geological timescale, humans advanced from using basic stone tools to examining the rocks on Mars; however, our exact evolutionary path and the relative importance of genetic and cultural evolution remain a mystery. Our cultural capacities—to create new ideas, to communicate and learn from one another, and to form vast social networks—together make us uniquely human, but the origins, the mechanisms, and the evolutionary impact of these capacities remain unknown.

Evolutionary biology is at an exciting juncture. Much important research has focused on the human genome as the key to unlocking knowledge about our evolutionary history. Recently, however, researchers have begun to recognize that understanding non-genetic inheritance, including culture, ecology, the microbiome, and regulation of gene expression, is fundamental to fully comprehending evolution. The evolutionary effects of culture, learning, and language have generated heated and dynamic debate and new interdisciplinary studies of human evolution. Now more than ever it is important to focus on the dynamics of cultural inheritance at different temporal and spatial scales, to uncover the underlying mechanisms that drive these dynamics, and to shed light on their implications for our current theory of evolution as well as for our interpretation and predictions regarding human behavior.

Many academic disciplines study human behavior and culture—anthropology, biology, psychology, computer science, ecology, economics, cognitive science, and archaeology, to name a few—often using different vocabularies. Two Stanford researchers, postdoctoral fellow Oren Kolodny and Professor Marc Feldman along with former Stanford postdoc Nicole Creanza, thought that researchers in these different fields could learn from one another to shed new light on human cultural evolution.

Their efforts to promote interdisciplinary work in human cultural evolution has led to a new theme issue in the world’s oldest scientific journal, Philosophical Transactions of the Royal Society B. In this special issue, Kolodny, Creanza, and Feldman aimed to combine perspectives from diverse fields to help elucidate the cultural forces affecting human evolution. The outcome is an interdisciplinary collection of research on the roles that culture plays in shaping the course of human evolution, exploring the mechanisms of cultural evolution from their cognitive underpinnings in individuals, through the behavioral ecology of learning from others, to the dynamics of transmission at the level of individuals and populations.

The issue also includes individual contributions authored by Kolodny, Feldman, Creanza, and co-authors, on the evolution of the human capacity for language, on linguistic cultural origins of the Creole language Sranan, and on the links between heritability, genes, and culture.

The sixteen new scientific publications in this issue were shaped by an international workshop entitled “New Perspectives in Cultural Evolution,” held at Stanford University in July 2016, supported by the John Templeton Fund. This workshop brought together researchers from multiple fields from different universities. With special focus on open discussions in large and small groups, participants in the workshop proposed new ways to synthesize fields, tackled current controversies, and highlighted important unanswered questions, leading to the new research published in the theme issue.

This research was supported by the John Templeton Foundation and the Stanford University Center for Computational, Evolutionary, and Human Genomics.

MAIN ISSUE PAGE:

http://rstb.royalsocietypublishing.org/content/bridging-cultural-gaps-interdisciplinary-studies-human-cultural-evolution

Table of contents when it goes live:

http://rstb.royalsocietypublishing.org/content/373/1743

PAPERS:

Kolodny O, Feldman MW, Creanza N (2018). Bridging cultural gaps: the interdisciplinary nature of cultural evolution. In press. Philosophical Transactions of the Royal Society of London: 20170413.

Kolodny O, Feldman MW, Creanza N (2018). Integrative studies of cultural evolution: crossing disciplinary boundaries to produce new insights. In press. Philosophical Transactions of the Royal Society of London: 20170048.

Feldman MW, Ramachandran S (2018). Missing compared to what? Revisiting heritability, genes and culture. In press. Philosophical Transactions of the Royal Society of London: 20170064.

Kolodny O, Edelman S (2018). The evolution of the capacity for language: the ecological context and adaptive value of a process of cognitive hijacking. In press. Philosophical Transactions of the Royal Society of London: 20170052.

Sherriah AC, Devonish H, Thomas EAC, Creanza N (2018). Using features of a Creole language to reconstruct population history and cultural evolution: tracing the English origins of Sranan (2018). In press. Philosophical Transactions of the Royal Society of London: 20170055.

MEDIA CONTACTS: Oren Kolodny tel: 650-665-3296 email: okolodny@stanford.edu, Marcus Feldman tel: 650-725-1867; e-mail: mfeldman@stanford.edu

Department of Biology, Stanford University, Stanford, CA

Nicole Creanza tel: 407-252-8361 e-mail: nicole.creanza@vanderbilt.edu

Department of Biological Sciences, Vanderbilt University, Nashville, TN

Fellows Feature: Arbel Harpak

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Arbel Harpak is a CEHG graduate fellow in Jonathan Pritchard’s lab. He holds BSc degrees in Mathematics and Physics, and MS degrees in Biology and Statistics.  In his PhD research, Arbel asks how mutational mechanisms and natural selection shape genetic variation.

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

I grew up in Israel. My family moved around quite a bit, but always kept a stone’s throw away from the beaches of the Mediterranean Sea, where I spent a lot of my time. I was very much into math and into wildlife from a young age, but hadn’t really thought of being an academic; no one in my family was, and playing outside with a ball of some shape or form filled up most of my schedule nicely. I only started my B.Sc. at 23, after a long military service, a short stint in industry, and some travel in Asia. While it sometimes feels like a late start compared to my fellow grad students, I am happy to have these bits of life experience outside Academia.

 I started my bachelor studies in Mathematics and Philosophy at the Hebrew University of Jerusalem, and, later on, added Physics to the mix. I deeply enjoyed my Math studies. I never knew—and probably never would have known without my Math education—how it feels to fundamentally and thoroughly understand your object of study. This feeling was a source of real joy for me.

My first research experience was in studying bacterial colony growth dynamics with the Physicist Nathalie Balaban during undergrad. This exposure to Biological research led to my M.Sc. work with Guy Sella (now at Columbia University). In my Masters, I developed theoretical expectations for genetic diversity in evolutionary experiments with micro-organisms, and conducted an experiment in the Balaban lab that tested these expectations. During this time, I got to read lots of inspiring research coming out of Stanford Evolution and Genetics labs; this led me to apply to join Stanford Biology’s Eco/Evo track.

How did you first become interested in genetics and science?

My Masters was probably the first time I started to seriously think about a career in research, mostly thanks to Guy Sella, who made the introduction to Population Genetics extremely exciting. He helped me form a reading list, starting from popular science books about evolution (e.g. Charles Darwin, Sean Carroll, Jerry Coyne and Neil Shubin) advancing into the fundamentals of Population Genetics and Coalescent theory (e.g. John Gillespie, Dick Hudson, Allen Orr, R.A. Fisher, Simon Tavaré, Charlesworths) and eventually contemporary research papers. He encouraged me to spend my first 4-5 months only reading, simulating evolutionary dynamics and periodically updating him on what I learned. In these conversations, he always thoughtfully guided me, but also had genuine interest in my own (probably quite naïve, in retrospect) thoughts. For me, this was a great experience that filled me with excitement for Population Genetics research.

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

Most of my doctoral work has been the study of mutational mechanisms, and how they shape human genetic variation. For example, analyzing >120K human exomes in the ExAC dataset, I found that many positions in the human genome were segregating mutations of more than one independent origin. This revealed substantial mutation rate heterogeneity even within what is considered a single mutation type.

What I like most about this work is being able to use large genomic variation datasets and Statistics to make discoveries about basic genetic mechanisms. The extent of mutational heterogeneity can be hard to quantify in direct experiments because of their limited sample sizes—but these huge genetic variation datasets contain evidence from a very long experiment: our own evolution.

I also work on the evolution of gene families. I helped develop riboHMM, a method with which we identified thousands of novel coding sequences in the human genome—some of which had surprising functions. For example, some of the novel sequences function as a regulatory “sink” of gene expression: they occupy Ribosomes and thereby reduce the expression of other genes. In more recent work, I estimated the rate of genetic exchange between gene duplicates. This exchange is a driver of >20 diseases and is also thought to be a central force behind the “concerted evolution” of gene duplicates—a curiously low level of divergence between duplicate genes that is sometimes observed long after their duplication.

What kind of responses have you gotten to your research/findings?

People are often excited to hear about my NYC rats research. This is a collaboration with Pleuni Pennings, Nandita Garud, Noah Rosenberg, Dmitri Petrov and Jason Munshi-South. New Yorkers (and people of other cities of course) are vividly aware that rats have adapted to urban environments impressively; we wanted to know whether this adaptation has a genetic basis. We have collected rats from abandoned lots around New York City and are scanning their genomes for unusual signs of adaptation. I love talking to people about this research because it illustrates evolution beautifully in comprehensible timescales, and with natural phenomena that one can see even in the most urban setting.

What happens next in the process of discovery?

Lately, my work has focused on highly-polygenic (“complex”) traits. Although most diseases and other traits are polygenic—i.e. affected by many different sites in the genome—most of our contemporary models and tools are best-fitted for a Mendelian world. Together, with lab mates who have already made significant discoveries in this area—Yair Field, Nasa Sinott-Armstrong and Evan Boyle—we are analyzing genome-wide association studies (GWAS) to learn about the genetic architecture of polygenic traits, and study this architecture’s implications on human evolution.

Are you enjoying your time at Stanford? 

Stanford is like Disneyland for academics. I can’t think of anywhere else I’d rather be for my Ph.D.

What is it like working with your current lab advisor and his lab?

More than anyone, my advisor, Jonathan Pritchard, is the person that shaped me as a scientist and has been a role model for me. He is a man of few, selected words who usually teaches by example: he is nearly always the quickest to identify the right questions to ask and the first to make sharp inferences. He strikes a balance between being constantly productive and engaged in everyone’s projects, and still managing to come up with innovations completely out of left field. I think a big part of this is his habit of occasionally zooming out—and taking the time to truly think and rethink about data critically.

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

Outside of research, I learnt everything I know from Tami and Eric Taylor.

Professionally? that’s such a long list. I am grateful to Stanford faculty that help with key advice along the way, notably Noah Rosenberg, Dmitri Petrov, Christina Curtis, Hunter Fraser and Marc Feldman.

Another large group that I owe a debt of gratitude to are my past and present fellow lab members. Just to give a few examples: I learned what true scholarship looks like from Ziyue Gao, Eilon Sharon, Jamie Blundell and Alison Feder; how to allow data to whisper secrets in your ear from Evan Boyle, Kelley Harris and Eyal Elyashiv; how high productivity and always making yourself available to help others can go hand in hand from Pleuni Pennings, Anand Bhaskar and Nasa Sinott-Armstrong; how to do statistical modelling that is revealing rather than hiding the signal in the data from David Golan, Anil Raj and Doc Edge; how to effectively communicate science from Emily Glassberg, Harold Pimental and Yang Li; this list goes much longer—but I should probably spare CEHG blog readers at this point.

Where do you see yourself professionally in the next 5 or 10 years?

I aspire to start my own research group and combine research with teaching. I would like to lead a group that investigates a biological question with whatever means necessary—a lab that is not too comfortable in its comfort zone. I am also quite passionate about teaching. I got to work as a high-school and college Math teacher to fund myself through my B.Sc. studies, and found it to be highly fulfilling. While I truly enjoy the footwork of applying statistical analysis to questions in Genetics and Evolution, I believe that the greatest impact I could have on the field is in teaching, advising and mentoring future generations; that is just how exponential functions work.

As a CEHG fellow, can you speak a bit to the role you see CEHG playing on Stanford campus?

I am proud to be a part of the CEHG community. CEHG brings together labs with shared interests from many departments at Stanford. Evolgenome seminars provide exposure to cool work and encourage interdisciplinary connections. I am particularly grateful for the generous CEHG fellowship—it allowed me to pursue my deep interest in the adaptation to urban environments in NYC rats and in polygenic trait evolution during the last year of my Ph.D.

CEHG’s core values include “interdisciplinary research” and “collaboration”. Can you speak to the ways your work has embodied these values or to their importance to your future work or past experience? How do these values align with your own approach to science?

In CEHG symposium 2016, I got to hear a talk by Christina Curtis and ask her many questions about it after. This conversation boosted a new research direction for me, and ignited brainstorming meetings with Christina Curtis and Zheng Hu and Ruping Sun from her cancer genomics lab. These meetings naturally developed into a collaboration with the Curtis lab in applying Population Genetics to better understand tumor progression. I feel quite fortunate to have been at the right place and time (= CEHG symposium 2016) that made this interdisciplinary connection possible.

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

If I had to identify one necessary but not sufficient condition for success in grad school, it is being excited about your research. It doesn’t have to be the research question; it could be the method or the people that you get to work with. Academic research careers can be very unrewarding externally, so if you are not internally fueled, grad-school crises might last years instead of weeks.

Other than that, I think it’s important to set high standards for yourself in what you want to excel at. For me, often times this means doing things painfully slowly—but from scratch and by myself.

Lastly, let me also confuse you with some contradictory-sounding piece of advice: get the most out of your colleagues’ experience, and give back as often as you can. I have personally learned that having science buddies—or better yet, science BFFs—is the single strongest determinant of my happiness in my work.

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? 🙂

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

Chuan Li 233_ForWeb

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.