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Sagi Shapira,PhD, assistant professor of systems biology at Columbia’s Vagelos College of Physicians & Surgeons and Nicholas Tatonetti, PhD, associate professor of bioinformatics and of systems biology at VP&S, have recently been awarded a new pilot grant to support their collaboration in COVID-19 research.

Drs. Shapira and Tatonetti are one of three teams who have been awarded a COVID-19 research pilot grant from the Herbert Irving Comprehensive Cancer Center. The pair will work on accurately identifying pathophysiological factors that modulate SARS-CoV-2 infection and explain variability in disease outcomes.

Read the full article here

Raul Rabadan , PhD, is an expert in uncovering patterns of evolution in highly dynamic biological systems, including in complex diseases like cancer. As the author of Understanding Coronavirus , a new book published by Cambridge University Press in June,  Dr. Rabadan, who originally began his academic career in mathematical physics, has set out to provide readers an accessible overview that quells misinformation about the novel virus, its origin, causes, and spread.

New Book by Raul Rabadan, PhD

Dr. Rabadan co-directs the Cancer Genomics and Epigenomics research program at the Herbert Irving Comprehensive Cancer Center (HICCC) , is professor of systems biology and of biomedical informatics at Columbia University Vagelos College of Physicians & Surgeons , and directs Columbia’s Program for Mathematical Genomics . He joined Columbia in 2008 right before the novel influenza, H1N1 or “swine flu”, emerged and quickly spread across the U.S. and the world.

At the time, Dr. Rabadan’s work honed in on understanding the genomic changes in a virus infecting a host and investigating how these changes contribute to the virus’ transfer to a different species. He continues to be fascinated by what can be gleaned from examining disease evolution.

When COVID-19 cases surged through the U.S., particularly in New York City in March, Dr. Rabadan—like many fellow scientists—contributed his research toward developing a treatment or vaccine. Scheduled to be on sabbatical this year, Dr. Rabadan instead remained quarantined with his family in New York City, shifting his attention to the new book and his own ongoing work in the genomics of cancer and COVID-19 research.

Read a Q+A with Dr. Rabadan, here

The seemingly chaotic bacterial soup of the gut microbiome is more organized than it first appears and follows some of the same ecological laws that apply to birds, fish, tropical rainforests, and even complex economic and financial markets, according to a new paper in Nature Microbiology by researchers led by Dennis Vitkup , PhD, associate professor of systems biology , at Columbia Univesrity Irving Medical Center .

One of the main challenges facing researchers who study the gut microbiome is its sheer size and amazing organizational complexity. Many trillions of bacteria, representing thousands of different species, live in the human intestinal tract, interacting with each other and the environment in countless and constantly changing ways.

"Up to now, it has been an open question whether there are any natural laws describing dynamics of these complex bacterial communities.”-Dr. Vitkup

The study’s discovery of multiple principles of gut bacterial dynamics should help researchers to understand what makes a gut microbiome healthy, how it may become perturbed in disease and unhealthy diets, and also suggest ways we could alter microbiomes to improve health. Read the full article in the CUIMC Newsroom. 

The study is titled “Macroecological dynamics of gut microbiota.” The other contributors are Brian W. Ji (Columbia), Ravi U. Sheth (Columbia), Purushottam D. Dixit (Columbia and University of Florida, Gainesville, FL), and Konstantine Tchourine (Columbia).

At first, Xuebing Wu , PhD, was on track to pursue a research career in computer engineering. After taking a course by Dr. Yanda Li, a pioneer of bioinformatics, Dr. Wu’s interest quickly shifted and he soon got hooked on genomics research and computational biology.

Xuebing Wu, PhD
Xuebing Wu, PhD

“Around that time—2003 to 2004—the human genome project had just been completed, and there had been lots of enthusiasm about using computational approaches to decipher the human genome,” he said. “I was excited to dive into this field that seemed wide open for research possibilities.”

Dr. Wu joined Columbia University’s Department of Systems Biology in the fall of 2018, with a joint appointment in the Department of Medicine’s Cardiology Division . He also is a member of the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian/Columbia and the Columbia Data Science Institute , and his lab straddles basic science and computational biology. Dr. Wu and collaborators often consider how their work can make an impact in novel therapeutics. 

At the center of his interests is understanding the fundamental principles of gene regulation in human cells through integrative genomics approaches. His previous work has uncovered important roles of RNA sequence and structure signals in controlling the expression and evolution of the mammalian genome. His lab currently studies RNA-centric gene regulation, focusing on mRNA structures and mRNA translation. Dr. Wu and his team are increasingly turning their attention to the development of genomic technologies such as the revolutionary CRISPR/Cas system and a high throughput analysis technology called massively parallel reporter assays (MPRA), as well as novel computational tools and deep learning models to study gene regulation at a global scale. 

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.

December 10, 2019

Highly Cited Researchers

Raul Rabadan Highly Cited
Raul Rabadan, PhD, (standing) with Francesco Brundu, postdoctoral research scientist in the Rabadan lab (Credit: Jeffrey Schifman)

Congratulations to Drs. Raul Rabadan and Xuebing Wu who were recently named a Highly Cited Researcher, according to the 2019 list from the Web of Science Group . Overall, Columbia University ranked 15th on the list of global institutions, with a total of 47 Highly Cited Researchers.

The Highly Cited Researchers list, which was released Nov. 19,  identifies scientists and social scientists who have produced multiple papers ranking in the top 1% by citations for their field and year of publication, demonstrating significant research influence among their peers.

Xuebing Wu, PhD
Xuebing Wu, PhD

Dr. Rabadan is professor of systems biology , with a joint appointment in biomedical informatics, at Columbia’s Vagelos College of Physicians and Surgeons . At Columbia, the Rabadan lab consists of an interdisciplinary team developing mathematical and computational tools to extract useful biological information from large data sets. In 2017, Dr. Rabadan established the Program for Mathematical Genomics , a multidisciplinary research hub that brings together researchers from the fields of mathematics, physics, computer science, engineering, and medicine, with the common goal of solving pressing biomedical problems through quantitative methods and analyses. He also serves as program lead for the Cancer Genomics and Epigenomics Program at the Herbert Irving Comprehensive Cancer Center at NYP/Columbia. 

Nicholas Tatonetti, PhD
Nicholas Tatonetti, Phd

Nicholas Tatonetti , PhD, solves problems. He has always enjoyed it, and as the informatics community has discovered, he is both creative and proficient in his methods.

Dr. Tatonetti, who was recently awarded tenure and promoted to the rank of Associate Professor in the Columbia Department of Biomedical Informatics (DBMI) and Department of Systems Biology , focuses on the use of advanced data science methods, including artificial intelligence and machine learning, to investigate medicine safety. Using emerging resources, such as electronic health records (EHR) and genomics databases, his lab is working to identify for whom these drugs will be safe and effective and for whom they will not.

His path to Columbia wasn’t a traditional one, but that fits his work. Since joining in 2012, Dr. Tatonetti has used non-traditional thinking to benefit both health and healthcare.

Utilizing both data mining of medical records and prospective lab experiments, Dr. Tatonetti created a methodology for both finding and validating adverse drug reactions and drug-drug interactions. During a two-year collaboration with Pulitzer Prize-winning journalist Sam Roe of the Chicago Tribune , Dr. Tatonetti discovered that the drugs ceftriaxone and lansoprazole, when taken together, induces an arrhythmia in the heart.

The data mining identified adverse effects, while the lab experiments established causality. Dr. Tatonetti wasn’t specifically looking for a negative reaction of those particular drugs; he had no reason to suspect them.

“We are able to find things that nobody expects to happen because the world of hypotheses we consider is basically everything,” he said. “We consider every possible combination, a type of analysis that would be impossible without a huge data set and significant computational power.”

Faculty

David Knowles

Assistant Professor, Department of Computer Science (in Systems Biology)

Assistant Professor, Department of Computer Science (in Systems Biology)

As a member of Columbia University’s Program for Mathematical Genomics (PMG) , Tal Korem, PhD, is bringing his interests in systems biology, quantitative research, and the human microbiome to areas of clinical relevance. For Dr. Korem, that clinical focus is women’s reproductive health. 

“There is still a lot we don’t understand that relates to women’s health, to fertility, and to birth outcomes, and how microbes play a role in all of this,” says Dr. Korem, assistant professor of systems biology, with a joint appointment in obstetrics and gynecology at Columbia University Vagelos College of Physicians and Surgeons. A current focus of the Korem lab is preterm birth, i.e., birth that occurs prior to 37 weeks of gestation, though Dr. Korem intends to expand into other areas such as infertility and endometriosis. 

Tal Korem, PhD
Tal Korem, PhD

Dr. Korem’s interest in  women’s health research is personal, stemming from several impactful experiences that hit close to home. 

“My aunt passed away from ovarian cancer and I have seen friends and family members struggle with idiopathic infertility,” he says. “Also, witnessing the complications with the birth of my first child, which involved emergency procedures, motivated my interest in this area, and I am very excited about the potential to contribute to women’s health with my own research.” 

Dr. Korem, a native of Tel Aviv, Israel, is the first in his family to earn a PhD, and had entered academia as a medical student. After completing  his undergraduate degree, he enrolled in a MD/PhD graduate program. There, he realized that research was what he enjoyed the most. He is a trained computational biologist, and studied under Professor Eran Segal at the Weizmann Institute of Science, where his work focused on the  human microbiome, a complex system of microbial communities that inhabit every body part. 

A wide range of research topics, from studies related to pediatric cancer and glioblastoma to soil microbial communities and electronic health records analysis—were presented and discussed at this year’s Department of Systems Biology (DSB) retreat. 

DSB Retreat 2019
Eugene Douglass, postdoctoral research scientist in the Andrea Califano lab, was one of the featured presenters at the two-day retreat. For a photo gallery, view the DSB Retreat Photo Album.

Held over two days for the first time, October 3 to 4 in Ellenville, NY, the retreat gave DSB faculty, post-docs, and students a chance to get away from the bustle of New York City, learn about their peers’ research, both from Morningside labs and CUIMC labs, and network. The department this year expanded its annual program over two days, encouraging more peer-to-peer connecting and devoted the spotlight specifically to research by young investigators. 

DSB researchers and graduate students participated in a poster competition held the first evening, and reviewed by Systems Biology faculty judges. At the end of the second day’s program, three Best Poster winners were announced by Andrea Califano, Dr, chair of the department. Poster competition winners this year were: Dafni Glinos , PhD, postdoctoral researcher in the lab of Dr. Tuuli Lappalainen at New York Genome Center/Systems Biology; Alexander Kitaygorodsky , a graduate student in the lab of Dr. Yufeng Shen; and Jordan Metz , an MD/PhD graduate student in the lab of Dr. Peter Sims. The poster winners gave presentations on the final day of the retreat and received a cash prize and an award certificate. 

Winning Research:

Dafni Glinos

Long-Read Sequencing to Study Allelic Effects on Transcriptome Structure

Dr. Tuuli Lappalainen Science Study

The illustration above depicts with an example of four genes, how knowing how variable genes are in the normal population helps to find candidate disease genes in a patient. Above, top: Tuuli Lappalainen, PhD; bottom: Pejman Mohammadi, PhD.

For individuals with rare diseases, getting a diagnosis is often a long and complicated odyssey. Over the past few years, this has been greatly improved by genome sequencing that can pinpoint the mutation that breaks a gene and leads to a severe disease. However, this approach is still unsuccessful in the majority of patients, largely because of our inability to read the genome to identify all mutations that disrupt gene function.

In a new study published on October 10 in Science , researchers from New York Genome Center , Columbia University , and Scripps Research Institute propose a solution to this problem. Building a new computational method for analyzing genomes together with transcriptome data from RNA-sequencing, they can now identify genes where genetic variants disrupt gene expression in patients and improve the diagnosis of rare genetic disease.

The new method introduced in this study, Analysis of Expression Variation or ANEVA, first takes allele-specific expression data from a large reference sample of healthy individuals to understand how much genetic regulatory variation each gene harbors in the normal population. Then, using the ANEVA Dosage Outlier Test, researchers can analyze the transcriptome of any individual – such as a patient – to find a handful of genes where he or she carries a genetic variant with an unusually large effect compared to what healthy individuals have. By applying this test to a cohort of muscle dystrophy and myopathy patients, the researchers demonstrated  the performance of their method and diagnosed additional patients where previous methods of genome and RNA analysis had failed to find the broken genes.

Tal Korem, PhD
Dr. Tal Korem

Tal Korem, PhD, has been named a CIFAR Azrieli Global Scholar, a fellowship that supports leading early-career researchers in science and technology. 

Dr. Korem is an assistant professor of systems biology with a joint appointment in obstetrics and gynecology at Columbia University Vagelos College of Physicians & Surgeons, and a faculty member of the Program for Mathematical Genomics . As a global scholar, he is joining CIFAR’s Humans and the Microbiome research program, where his work will focus on harnessing human microbial communities to identify and develop novel diagnostic and therapeutic tools.

CIFAR’s  Azrieli Global Scholars program supports its fellows through funding and mentorship, emphasizing essential network and professional skills development. The scholars join CIFAR research programs for a two-year period where they collaborate with fellows and brainstorm new approaches to pressing science and technology problems. Research topics are diverse, ranging from bio-solar energy and visual consciousness to engineered proteins and the immune system. 

Dr. Korem is one of 14 researchers out of an applicant pool of 217 selected by the Canadian-based nonprofit organization. This year’s cohort represents citizenship in eight countries and appointments in institutions from Canada, the U.S.,  Israel, Australia, the Netherlands, and Spain.

-Melanie A. Farmer

Newly Tenured Faculty
Awarded tenure this year in the Department of Systems Biology, left to right: Dr. Nicholas Tatonetti, Dr. Yufeng Shen, and Dr. Chaolin Zhang.

Congratulations to Drs. Yufeng Shen, Nicholas Tatonetti, and Chaolin Zhang of the Department of Systems Biology, who have been awarded tenure and promoted to associate professor. Their new appointments are effective July 1, 2019. 

Yufeng Shen, PhD

Dr. Shen joined Columbia University Irving Medical Center in 2011 as an Assistant Professor in Systems Biology and Biomedical Informatics. He directs a research group focused on studies of human biology and diseases using genomic and computational approaches. They are developing new methods to interpret genomic variations by machine learning based on biological mechanisms, and using these methods in large-scale genome sequencing studies to identify new genetic causes of human diseases, such as autism, birth defects, and cancer. His group also works on modeling of clonal and transcriptional dynamics of immune cells to improve our understanding of human adaptive immune system under normal and clinical conditions. Dr. Shen serves as an Associate Director of the JP Sulzberger Columbia Genome Center, a member of the Program in Mathematical Genomics, and an adjunct member of Columbia Center for Translational Immunology. 

Nicholas Tatonetti, PhD

Dr. Tatonetti, whose primary appointment is in the Department of Bioinformatics, has an interdisciplinary appointment with both the Departments of Systems Biology and Medicine. Dr. Tatonetti’s lab specializes in advancing the application of data science in biology and health science. His group integrates their medical observations with systems and chemical biology models to not only explain drug effects, but also to gain further understanding of basic biology and human disease.

Dr. Harris Wang of Systems Biology
Dr. Harris Wang is lead PI on a new DARPA-funded project developing novel therapies to counter effects of high-dose ionizing radiation.

Harris Wang, PhD, assistant professor of systems biology at Columbia University Irving Medical Center , is leading a team of experts in radiation research, CRISPR-Cas technologies, and drug delivery on an innovative new project announced June 27 funded by the Defense Advanced Research Projects Agency (DARPA) . The up to $9.5M project focuses on pursuing a therapy to protect the body from the effects of high-dose ionizing radiation, and is part of DARPA's initiative to fund research into new strategies to combat public health and national security threats.

In humans, acute radiation syndrome primarily affects stem cells in the blood and gut, yet existing treatments only help to regenerate blood cells, and only with limited effect. There is no possibility for prophylactic administration of these drugs, and most must be delivered immediately following radiation exposure to provide any benefit. There are no existing medical countermeasures for radiation damage to the gut.

The Columbia team aims to develop an orally delivered programmable gene modulator therapeutic. The multimodal treatment the team envisions would take hold in both the gut and liver, triggering protection and regeneration of intestinal cells, while also inducing liver cells to produce protective cues that trigger the regeneration of blood cells in bone marrow.

Columbia investigators win Chan Zuckerberg Initiative grants to accelerate development of cellular roadmap of the human body.

In two groundbreaking research projects contributing to the Human Cell Atlas, Columbia University scientists are tasked with mapping complete cells in the immune system and the human spine. The global effort is aiming to identify and define every cell type of the human body and create a collection of maps for navigating the cellular basis of human health and disease.

Peter Sims, PhD
Peter Sims, PhD, assistant professor of systems biology

The Columbia teams, which include co-principal investigators from the Department of Systems Biology Drs. Peter Sims and Raul Rabadan , are among the 38 collaborative science teams launching the Chan Zuckerberg Initiative’s (CZI) Seed Networks for the Human Cell Atlas project announced today. The three-year projects, receiving a total of $68 million in award funding by Seed Networks, are collaborative groups that are bringing together expertise in science, computational biology, software engineering, and medicine to support the ongoing progress of the Human Cell Atlas .

Investigating the Immune System + Aging

Dr. Sims, part of an international team including close collaborator Dr. Donna Farber of the Department of Surgery , is combining single-cell sequencing technologies, data analysis, and immunology expertise to better understand how the immune system ages and gain new insights into how human diseases occur. 

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