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Andrea Califano
Andrea Califano identifies 'master regulators' of cancer cells. (Credit: Tim Lee Photographers)

Genomics has revolutionized cancer research. Conventional classifications of disease, in terms of which organs and tissues it affects, are being divided into subtypes defined by the specific mutations that drive the disease. Some argue, however, that the impact on cancer care has not lived up to expectations. “Only about 5–10% of cancer patients derive any benefit from targeted therapy using genetics, and almost all of them eventually relapse,” says Andrea Califano , Dr, chair of the Department of Systems Biology at Columbia University Irving Medical Center. “The number that are actually cured is extremely small.”

Developing a genetically targeted therapy is no easy task. It can be tricky to identify which genetic mutations are driving the cancer and which are passengers — those that are statistically linked, but that do not cause cancer. And although developers of targeted therapies focus mainly on mutations to a subset of genes called oncogenes, there is more to malignancy. Read the full Nature Outlook article here

In recognition of Dr. Andrea Califano's recent Ruth Leff Siegel Award , an annual prize that honors and supports an investigator who has made outstanding contributions to our understanding of pancreatic cancer, Let's Win! Pancreatic Cancer has published the following feature article spotlighting his innovative approach to cancer research.

Dr. Andrea Califano
Dr. Andrea Califano, 2019 recipient of annual Ruth Leff Sigel Award for pancreatic cancer research. (Photo: Jörg Meyer/Columbia Magazine)

If you look at our basic biology, humans are big, cumbersome living organisms with a lot of moving parts.

For most of our lives, the cellular machinery that keeps us functioning goes off without a hitch. Starting at conception, cells have been growing and dividing, structuring themselves in a highly organized fashion. Liver cells know their job. And brain and spinal cord cells know their jobs, too.

Cancer is also a living organism. After all, it grows and evolves just like healthy cells. But cancer cells are cheats, ignoring the rules that other healthy cells play by. They mutate and divide uncontrollably, finding ways to evade our immune systems, which try to keep these invaders in check. To complicate matters, cancer cells are what scientists call heterogeneous. That means that even in the same malignant tumor there can be a variety of mutations, which is one reason why cancer treatment often fails. Drugs simply can’t target all of those mutations.

 

Andrea Califano
Andrea Califano, Dr

The migration away from “one-size-fits-all” medicine, particularly in the areas of cancer detection and treatment, holds great promise for patients and the field of precision medicine. Demand and jobs are increasing for researchers, clinicians and professionals who are at home collecting, analyzing and using more and newer forms of data, according to a recent feature reported in Science magazine which spotlights Dr. Andrea Califano , founding chair of the Department of Systems Biology

In the field of oncology, innovations continue to grow rapidly in precision, or targeted medicine, as clinicians seek to find better treatments for specific kinds of cancer, rather than take a blanket approach via the traditional trifecta of radiation, chemotherapy, and surgery. To do so, they must test patients, note mutations, and identify biomarkers to determine what treatments could work best with the fewest side effects.

Scientific breakthroughs, in these areas and more, have led to greater understanding of genes and their functions and have created new opportunities for precision medicine—and for those with technical, research, and clinical skills eager to work in this ever-expanding field. Special consideration will be given to those job applicants who can perform big data analysis and multidisciplinary research. However, new jobs will also emerge in previously unseen areas, such as business, translational medicine, and genetic counseling.

New and powerful tools have aided the precision medicine movement. The Human Genome Project, the first complete mapping of human genes, published its preliminary results in 2001. The project’s numerous benefits include knowing the location of the approximately 20,500 genes identified in the body and gaining a clearer understanding of how genes areorganized and operate.

An essay coauthored by Andrea Califano (Chair, Department of Systems Biology) and Gideon Bosker and published in the Wall Street Journal asks whether quantitative modeling could reveal the keys for turning cancer off. They write:

  • Disappointed with the slow pace of discovery and inclined to look for elegant, universal explanations for nature’s conundrums, many cancer researchers have increasingly been asking: Is there some sort of “Da Vinci Code” for cancer? And can we crack it using mathematics?

    Quantitative modeling has been extremely successful in disciplines as diverse as astronomy, physics, economics and computer science. Can “cancer quants”—scientists applying quantitative analyses to the landscape of cancer biology—find the answers we seek? And, if so, what would the new paradigm look like? 

The essay goes on to describe how computational methods developed in the Califano Lab are being tested in personalized N of 1 clinical trials to identify essential checkpoints in the molecular regulatory networks that sustain individual patients' tumors — as well as drugs capable of targeting them.

Click here to read the essay. (subscription may be required)

Economic Markets and Biological Markets

In a similar manner to the ways in which countries make and trade goods, microbial cells within bacterial communities exchange metabolites to promote cell growth. This perspective could provide a way of studying microbial communities from the perspective of economics.

An article in the Wall Street Journal reports on a recent collaboration involving Columbia University Department of Systems Biology Assistant Professor Harris Wang and Claremont Graduate University economist Joshua Tasoff that identified some intriguing similarities between economic markets and the exchange of resources among microbes within bacterial communities. 

In an unusual marriage, biology and economics appear to be a match made in heaven.

Four years ago, two former roommates reunited at a friend’s wedding had time to catch up. The first, an economist, asked: “What are you working on?” The second, a biologist, answered: “How microbial communities interact. It’s kind of like in economics.”

And that’s when the intellectual sparks began to fly.

Turns out microbial communities—what most of us think of as germs—expand by trading metabolites such as amino acids with other species of bacteria, just like free-market economies grow by exchanging goods and services.

That novel insight, inspired by a chance conversation and supported with research developed over the intervening years, provides a framework to explain how different species of bacteria interact in complex communities.

You can read the entire article here: Economies of Ail: How Bacteria Flourish. [login may be required]

Related publication

Tasoff J, Mee MT, Wang HH. An economic framework of microbial trade. PLoS One. 2015 Jul 29;10(7):e0132907.

Kyle AllisonKyle Allison, a Systems Biology Fellow in the Columbia University Department of Systems Biology and recent winner of a National Institutes of Health Early Independence Award, is featured this week in a blog post authored by NIH Director Francis Collins. The article highlights Dr. Allison’s ongoing efforts to use approaches based in systems biology to understand bacterial persistence, a phenomenon that in clinical settings can often lead to dangerous, difficult-to-manage infections.

Read the complete post here: Creative Minds: Searching for Solutions to Chronic Infection.

Personalized Medicine

Illustration by Davide Bonazzi, courtesy of Columbia Medicine.

The cover article of the Spring 2014 issue of Columbia Medicine reports on a new, Columbia University-wide effort to harness the potential of new scientific approaches and technological developments to advance the personalized treatment of cancer and other diseases. Announced in February by Columbia President Lee Bollinger, an interdisciplinary task force has been formed to coordinate the scientific, policy, and clinical components necessary to achieve this goal. The Department of Systems Biology, including its Center for Computational Biology and Bioinformatics and JP Sulzberger Columbia Genome Center, has been identified as a key partner in this interdisciplinary effort. As the article reports:

Rapidly evolving technologies that make DNA sequencing dramatically faster and less expensive along with new technologies to monitor virtually all aspects of cell physiology have led to the generation of unprecedented amounts of information (big data) that is starting to yield to new computational approaches and high speed computers, all of which promise to make diagnosis and treatment as patient-specific and precise as possible.

To harness the potential created by these scientific advances for the benefit of patients, [College of Physicians & Surgeons] Dean Lee Goldman, MD, has made personalized medicine a key goal of the medical school’s strategic plan. “At Columbia, we have enthusiastic consensus in support of personalized medicine—the personalized application of scientific advances to modern diagnosis and treatment, easily accessible and attentive care for the people who entrust us with their health, and personalized education for each of our individual students,” says Dr. Goldman…

At the center of Columbia’s personalized medicine effort is the new Department of Systems Biology, which brings together researchers specializing in molecular biology, genetics, computational biology and bioinformatics, structural biology, mathematics, chemistry and chemical biology, physics, computer science, and other fields. According to founding director and chair Andrea Califano, PhD, the Clyde and Helen Wu Professor of Chemical Systems Biology, the new department seeks to provide an in-depth, systemwide characterization of all molecular interactions. It is this systems-level approach to disease biology that can systematically identify disease drivers and druggable targets for the 90 percent of cancer patients who lack a clearly actionable genetic mutation. This has become possible only in recent years through major advances in science and technology that require a fully interdisciplinary approach.

The article describes how research by Department of Systems Biology faculty members including Dr. Califano, Nicholas Tatonetti, Brent Stockwell, and Tuuli Lappalainen, along with that of investigators in departments across the university, is contributing to this ambitious initiative. Read the complete article here.

Chris Wiggins

In a “Most Creative People” feature, Fast Company magazine recently interviewed associate professor Chris Wiggins, a faculty member of the Department of Systems Biology and Center for Computational Biology and Bioinformatics, about his new appointment at one of the world’s most respected outlets for digital journalism. In this role, he will lead the development of a machine learning team that will help the New York Times to better understand how its audience is using and navigating its content.

In the interview Dr. Wiggins explains why machine learning is becoming increasingly important in the age of big data, and about the shared challenges that the natural sciences and the media are now both facing.

The magazine Genetic Engineering & Biotechnology News has published an article reporting on several talks given at the recent Department of Systems Biology Inaugural Symposium.

Author Richard A. Stein writes:

“Science is more than a body of knowledge, it’s a way of thinking,” remarked Carl Sagan, and probably his words were never more powerfully relevant than for portraying one of the newest biomedical fields, systems biology.

A recent symposium inaugurating the department of systems biology at Columbia University Medical Center comes at a very auspicious time, one in which biomedical sciences, chemistry, physics, engineering, bioinformatics, and computer sciences are converging to shape a vibrant new discipline.

The article includes summaries of presentations by Department of Systems Biology faculty members Barry Honig (protein-protein interactions), Saeed Tavazoie (gene expression dynamics), Virginia Cornish (synthetic chemistry using yeast), and Peter Sims (high-throughput single-cell measurement), as well as keynote speaker James Collins (antibiotics and the microbiome).

You can read the full article here.