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September 15, 2022

Welcome, Dr. Sara Zaccara

The Department of Systems Biology at Columbia University Irving Medical Center welcomes new faculty member Sara Zaccara, PhD. Dr. Zaccara joins Columbia as an assistant professor, effective Sept. 1. Prior to coming to Columbia, she was a postdoctoral researcher at Weill Cornell Medicine.

Dr. Zaccara grew up in a small town in Italy. She received her PhD from the University of Trento, in Trento, Italy, where her thesis work was on p53-dependent translational regulation. She received her bachelor’s and master’s degrees in biotechnology from the University of Florence. “I studied biotechnology,” she says, “because I was fascinated by the idea of developing new methods that could improve our future in medicine.”

Dr. Zaccara’s research focuses on the intricate cellular mechanisms that control the chemical tag called m6A, which cells insert into almost 30 percent of their mRNA molecules. She has proposed a unified model of how m6A mRNAs are controlled in cells. She also helped show why the number of m6A sites in mRNAs has functional consequences for mRNA fate.

Currently, Dr. Zaccara’s group is working on characterizing the mechanisms that trigger m6A mRNA degradation in normal and disease states, in particular, acute myeloid leukemia. The group is also investigating the impact of the functional specialization of RNA binding proteins on mRNA fate. Their multidisciplinary approach includes the use of CRISPR-Cas9 base editor screens, massively parallel tethering screens, molecular tagging, imaging, and in vitro experiments. The integrated combination of these methodologies will enable investigation of critical components of the mRNA degradation pathway and their contribution to mRNA fate with unprecedented throughput and resolution.

Faculty

Sara Zaccara

Assistant Professor, Department of Systems Biology

Assistant Professor, Department of Systems Biology

Faculty

Nikhil Sharma

Assistant Professor, Department of Molecular Pharmacology and Therapeutics

Assistant Professor, Department of Systems Biology

Assistant Professor, Department of Molecular Pharmacology and Therapeutics

Assistant Professor, Department of Systems Biology

Raul Rabadan, PhD, professor of systems biology and of biomedical informatics, has been named a 2020 Highly Cited Researcher by Clarivate. Announced Nov. 18, Dr. Rabadan is one of 45 Columbia University faculty members who were selected for the annual list. 

The Highly Cited Researchers annual report recognizes researchers who have had major impacts in their fields. To be named to the list, researchers must produce multiple papers ranking in the top 1% globally by citations for their field and year of publication, demonstrating significant research influence among their peers.

Dr. Rabadan, founding director of Columbia's Program for Mathematical Genomics, also was named to the list in 2019, along with fellow Systems Biology faculty member, Xuebing Wu, PhD.

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

Mohammed AlQuraishi, PhD

The Department of Systems Biology at Columbia University Irving Medical Center is pleased to welcome new faculty member, Mohammed AlQuraishi , PhD, effective Sept. 21. Dr. AlQuraishi joins Columbia as an assistant professor and as a member of Columbia’s Program for Mathematical Genomics. 

Prior to joining Columbia, Dr. AlQuraishi served as a fellow of systems pharmacology and systems biology at Harvard Medical School. He completed his PhD in genetics and master’s in statistics from Stanford University. At Santa Clara University, he earned two bachelor’s degrees in biology and in computer engineering. 

A Bay Area transplant via Baghdad and Kuala Lumpur, Dr. AlQuraishi spent most of his teenage years in the San Francisco Bay Area before moving to the east coast for postdoctoral work. Influenced by the dot-com boom of the early 2000s in the Bay Area, Dr. AlQuraishi founded two startups in the mobile computing space before focusing on a career in academia. His circuitous path to systems biology and academic research ultimately blended his genuine interest and expertise in computer programming, mathematics, molecular biology, and science more broadly.

“What drew me to biology is its similarity to software, the fact that cells are always executing a sort of program," he says. "And just like programs, cells are more than a parts list—they are complex and interconnected in myriad ways. To tame this complexity we need synthesis, and that is the promise and challenge of systems biology.”

Faculty

Mohammed AlQuraishi

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

One of the immune system’s oldest branches, called complement, may be influencing the severity of COVID disease, according to a new study from Drs. Sagi Shapira and Nicholas Tatonetti at the Department of Systems Biology.

Drs. Sagi Shapira (right) and Nick Tatonetti
Drs. Nicholas Tatonetti (left) and Sagi Shapira

Among other findings linking complement to COVID, the researchers found that people with age-related macular degeneration—a disorder caused by overactive complement—are at greater risk of developing severe complications and dying from COVID.

The connection with complement suggests that existing drugs that inhibit the complement system could help treat patients with severe COVID-19.

The study was published in Nature Medicine . For the full article , visit the Columbia University Irving Medical Center Newsroom. 

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

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