Celebrating its Unique Program, Establishing a New Tradition with Alumni
“We have a deep understanding of biology at both the molecular level and the systems level. It’s like seeing two sides of the coin simultaneously. And we and our alumni can now tackle problems that were unsolvable ten years ago.” –James Chen, PhD, Chair, CSB (July 2018)
James Chen, PhD, opened the reunion talking about the Chemical & Systems Biology community, “We are a living community, connected by our passion for science.” As proof, he showed a 2003 photo of department faculty and trainees, clad in faded t-shirts and jeans, standing in front of the library. Next, he displayed today’s department in an updated photo. “We are still together,” said Chen with a smile, looking up at the smartly-dressed group. “But much better dressed than we were fifteen years ago!” The audience of faculty, alumni, and trainees laughed.
Chen continued, “And best of all, everyone is employed! Of our 200 alumni, more than half are still in California,” he paused, “perhaps some of you should fall further from the tree?” More chuckles.
On a more serious note, Chen spoke about their shared academic legacy, “the family tree of scientific fathers, mothers, sisters and brothers” and how connected the community is, and how it grows and changes — while always recognizing that “the most important outcome of the department has been and continues to be its people.”
He noted the breath of careers that alumni are pursuing. They are now senior scientists working across the biomedical career spectrum: academics running their own labs, scientists doing basic science and translational research in biotechnology companies, entrepreneurs and venture capitalists, patent attorneys, and policymakers at the NIH.
Chen believes they are especially well prepared for this brave new world of biomedicine. “To advance biology and medicine today,” he said, “you need to have both molecular and systems-level insights. You also need technologies that can provide a mechanistic, quantitative understanding of biological processes.”
Alumni Journeys
“Our alumni are essential to our community,” said Chen announcing that this reunion is the first of a new CSB annual tradition.
In fact, this first reunion was all about alumni coming to tell their stories to the current graduate students and postdocs. To tell what they had learned about the importance of mentorship, networking and finding one’s own unique path to a career. The three alumni speakers also echoed Chen’s sentiment about the importance of community and how it extends into their professional lives.
The alumni described how their individual journeys took unexpected and fruitful turns when they pursued new opportunities not previously considered. They provided insight about the inner workings of pharmaceutical research, how many discoveries are being made and the critical stages of drug development. They described the opaque world of scientific journals and the exacting editorial process that is imposed on researchers to ensure that their research studies are properly vetted before being published.
Joshua Lichtman, PhD, who graduated three years ago and is now a senior scientist at NGM Biopharmaceuticals, said, “It’s cool to come back to Stanford. We are happy to talk to graduate students and postdocs about our work — and how we got there, how we helped each other. They also need to know that the biology in industry is as much an intellectual challenge as it is in academia. The biology is still really hard!”
In Lichtman’s case, he has worked in metabolic disease and cancer research, discovering and validating new therapeutic targets through a combination of computational and molecular approaches. But Lichtman didn’t start out doing this. He first worked at a biofuels company, looking at how microbes affect production and recovery of subsurface hydrocarbons. Then, at Stanford, he researched the interaction between the microbiome and host.
Fast forward to his work at NGM, where, as a molecular biologist with some computational know-how, he started doing computational biology for many other NGM scientists working in a range of areas from proteomics to oncology. “I started doing analysis for lots of people because they didn’t have this skill set within the company.” He now leads informatics at the company and supports all facets of research and development through the implementation of computational tools.
Lichtman credits the SPARK program that teaches project management in applied research, with giving him the additional professional skills necessary to take on the outside world. “I’m an avid SPARKee,” he said. “It gave me a new way to think about science, an understanding of how projects develop over time.”
Tiago Faial, PhD, senior editor, Nature Genetics, has pursued a different career path helping to guide some 200 scientific papers through the publication process annually for his journal. Faial, who hails from a stem cell and developmental biology background and was a CSB postdoc researching chromatin and epigenetics, gave the assemblage a look at the often-mysterious editorial process. Heading up this prestigious publication is no small intellectual task, as he and his team help to decide among the nearly 1,400 articles that are submitted each year.
Faial described the criteria that he, as editor, has to consider: Does the article fit the editorial mission and focus of the journal? For example, does the article focus on the genetic basis of disease or emerging areas? Is the work groundbreaking in that it will help other scientists change the way they do their research? Is the research technically sound? Are all the claims supported by data? What are the implications for the study’s findings? What is known, what is not known? Once through the initial assessment stage, then the articles are sent out for commentary.
When asked for an example of how papers are evaluated, Faial described how he looks for studies that have broader implications for scientists. He mentioned one such study that raised a new concern about a type of virus that has been used for years as a therapeutic vector. The virus is deemed to be safe, but this new study presented findings showing that the wild-type virus integrates itself into the DNA of patients’ livers. Importantly, the study found the virus present in individuals with liver cancer. “These are important new data,” he said. “This virus, in fact, could be pathogenic.”
Faial talked about editorial meetings where staff gathers to present cases for selected articles and debate which should ultimately be published. Considering the fact that over 80% of the submissions are rejected, this is a strenuous process.
Philip Vitorino, PhD, senior scientist, Abbvie, has seen a good deal of variety within biotech as he has moved from large companies to small. He has worked in positions focused on very basic research and also led projects where the goal is to optimize the efficacy of therapies already in the clinic. He explained the stages of drug development and how he has built expertise in these stages as his projects and career evolved.
The entire process starts with discovery, the intensive research stage where a drug target is identified. The next stage is target validation, a data-focused process that precedes a company’s decision to develop a small molecule or biologic therapy. Once a drug is identified against the target, the next major phase is translational and pre-clinical development, a stage focused on human dose estimation, biomarker discovery, and regulatory filing with the FDA. The final phase is clinical which consists of sequential Phase I, II, and III clinical trials that test safety and efficacy of the drug in humans and, when positive, leads to FDA approval.
At Genentech, he worked in vascular biology, understanding how blood vessels dynamically develop, or “sprout,” to heal wounds in healthy tissue but also support tumors or create diabetic retinopathy in the disease setting. He investigated how MAP4K4, a kinase signaling protein, regulates the development of new blood vessels in order to develop a potential drug target. At Gilead, he researched BET, a DNA binding protein that controls gene activation, as a pharmacological target for cancer. Now, at Abbvie, he is examining antibody-based drugs to target tumors. The antibodies, which carry a chemical agent, are able to identify a target on the surface of specific cells, such as cancer cells. The chemical agent is taken up by those cells, and once inside, is released to either modify the cell behavior or to kill the cells. Since the antibody is only taken up by targeted cells, any drug side effects or risks to other cells in the body are significantly reduced.
Lessons Learned
The alumni spoke about their lessons learned, everything from networking, to broadening their knowledge base, to learning how to communicate their science.
Networking was high on their lists. “Start early and talk to people,” said Lichtman. Someone I collaborated with at my prior lab brought me into NGM.” Vitorino heartily agreed, “The top scientists in the world are here at Stanford. Talk to them! Network! I got all my jobs — at Genentech, Gilead, and Abbvie – by networking with the Stanford community.”
Lichtman, who did an internship at NGM before being hired, said, “Internships are a great way to get in the door.”
“Broaden your knowledge,” said Faial. “Go to seminars outside your specialty. Ask questions.” Vitorino agreed and added that you can explore new research areas too. “Be flexible,” said Vitorino. “You are not confined to one subject. You can move among different areas, for example, go from an oncology group to a fibrosis group.”
Learn to tell your story,” said Lichtman. “You may have done impressive research, but you have to be able to explain it. You need to show what you think about the science, not just what you do. Ignore the fear about doing something new.”
When asked about how scientists are recognized in an industry where many treatments typically do not reach clinical trials, Lichtman and Vitorino said that you are evaluated on the quality of your project, on how well you meet your objectives, and how you work with a team.
Break with Tradition
In reflecting about the CSB department, Chen said, “Our department is unique when compared to basic science departments at other academic institutions.” He referred to the fact that Stanford had the foresight in 2006 to combine the two formerly distinct disciplines of chemical biology and systems biology into one department. “Our trainees have both the molecular and systems-level knowledge.”
Why is this important? Chen explained, “Basically, you have to deconstruct complex biological systems, and to do this, you need to have a multi-dimensional view.” In other words, to look at both sides of the equation, from the micro level of molecules up to the macro level of entire systems.
“We can now tackle problems that were unsolvable ten years ago,” said Chen, “because we are empowered by new research tools and a more integrated, holistic view of biology. We can pursue fundamental questions, such as: How does a single cell develop into a complex organism? What are the pathways that regulate cell growth and cell death? What are the differences between healthy and diseased states?”
James Ferrell, MD, PhD, professor of chemical and systems biology and of biochemistry, described how it works. “On one side, in chemical biology, you take a ‘reductionist view.’ You study one molecule, one protein, or gene, to understand the characteristics and function of individual components. Understanding the basic elements then enables you to piece together multi-component systems. On the other side, in systems biology, you study complex networks or sub-circuits of many proteins and genes. You may have 100 molecules or activities that are involved, and you want to look at the combined effect of all of them functioning simultaneously. Our ultimate goal is to understand the overall design principles of living systems, to understand the simple principles that give rise to the behaviors of complex biological systems.”
As an example of how beneficial it is to have both perspectives when studying human biology, Ferrell recently published a study describing how trigger waves guide cell death like a wave rippling throughout the cell. He found that once cell death is initiated by disease or other action, trigger waves, a type of cell regulation, continue the process as killer proteins get activated and, in turn, activate other killer proteins in a continuing sequence throughout the cell. Inactive molecules are converted into active molecules. He believes if we learn how cell death, or apoptosis, is regulated, we will be able to intervene to start or stop the process.
“Since we can approach these biological problems from many different angles,” said Chen, “we can better understand their molecular and quantitative underpinnings.” He cited the advances in genome sequencing and editing, protein engineering, chemical synthesis, and data analysis that are propelling this field forward. “We are training our students to integrate genetic technologies, biochemical and chemical tools, quantitative measurements, and computational modeling.”
Marisol Urbano,who spent eight years managing department events and alumni relations, summed it up, “Because our trainees can see every aspect of biological development – from the molecular level on up to the systems level — they can then better apply the chemistry to the human system.”
Like his alumni, Chen has had his own unique journey to his present position: From first scrutinizing crawdads in a Missouri creek, to Harvard for his undergraduate and PhD studies, and then to Stanford where he now leads an interdisciplinary research group and serves as the CSB Chair.
He even volunteered for the dunk tank at the alumni reunion barbecue, as many trainees enthusiastically lined up for a chance to dunk the Chair.
The CSB community is embracing the new frontiers of their field on all fronts. As Lichtman said, “We are following the biology wherever it takes us, and we are making many novel discoveries.”
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By Nadine Taylor-Barnes
Biosciences Sr. Communications Consultant
Stanford University School of Medicine