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Raul Rabadan Highly Cited
Raul Rabadan, PhD, (standing) with research scientist from the Rabadan lab (Jeffrey Schifman Photo)

Congratulations to Dr. Raul Rabadan who was 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.

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 

Core Faculty, New York Genome Center

Assistant Professor, Department of Computer Science 

Core Faculty, New York Genome Center

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. 

Chaolin Zhang
Chaolin Zhang, PhD, associate professor of systems biology

A new study by researchers in Dr. Chaolin Zhang’s lab at Columbia’s Department of Systems Biology details a novel computational method that models how RNA-binding proteins (RBPs) recognize specific sites in the target RNA transcripts, precisely and accurately. The researchers’ findings include identification of entirely new motifs (RNA sequence patterns), and their research in complex RNA regulation contributes to our understanding of the molecular basis of disease and conditions, and down the road, could aid in the development of targeted therapies. 

The study, led by Dr. Zhang, associate professor of systems biology, with senior co-authors Suying Bao, PhD, and Huijuan Feng, PhD, appears today in Molecular Cell

RNA has traditionally been considered mere “messengers” that transfer genetic information from DNA to proteins that ultimately carry out cellular functions. However, it is now increasingly appreciated that RNA can be tightly regulated to control gene expression and diversity protein products. RNA-binding proteins (RBPs) are at the center of such regulation, with important roles in many cellular processes, including cell function, transport, and location. Gaining mechanistic insights of the binding specificity of RBPs in a genome-wide scale helps advance our knowledge of gene regulation.

“RNA-binding proteins are crucial for gene expression,” says Dr. Feng, coauthor of the study and post-doctoral research scientist in the Zhang lab. “RNA is heavily regulated, and when this regulation goes wrong, instabilities or disease could occur.”  

Dr. Andrea Califano sits down with BioTechniques at AACR. Video: Courtesy of BioTechniques.

At the 2019 annual meeting of the American Association for Cancer Research (AACR), Dr. Andrea Califano sat down with BioTechniques News for an overview on the field of systems biology and its impact in cancer research and in precision medicine. Dr. Califano is a pioneering researcher in the fast-growing field of systems biology whose expertise is in developing innovative, systematic approaches to identify the molecular factors that lead to cancer progression and to the emergence of drug resistance at the single-cell level. A physicist by training, Dr. Califano is the Clyde and Helen Wu Professor of Chemical and Systems Biology, founding chair of the Department of Systems Biology at Columbia University Irving Medical Center, director of the Columbia Genome Center and a program leader at the Herbert Irving Comprehensive Cancer Center.

The video interview is part of the series, Behind the Technqiue by BioTechniques News. 

Oxytricha

New research by Laura Landweber, PhD, who has joint appointments in the Department of Biochemistry and Molecular Biophysics, the Department of Systems Biology and the Department of Biological Sciences at Columbia University, is being featured by Columbia Univeristy Iriving Medical Center Newsroom.

As reported, a new study of a single-celled eukaryote with 16,000 tiny chromosomes may shed light on a recently discovered feature of the human genome.

Methyladenine, or 6mA—a modification of DNA common in Oxytricha trifallax—has only recently been found in multicellular organisms, with some studies suggesting a role in human disease and development.

Finding the enzymes that lay down the methyl marks will be critical to understanding what 6mA is doing in Oxytricha and other organisms, but the enzymes have been difficult to identify.

The new research—to be published in the June 13 issue of Cell—reveals how 6mA marks are made to the Oxytricha genome and suggests why the enzymes have been hard to find.

Read more about the Oxytricha genome and the Landweber lab’s new insights into 6mA and its potential role in human diseases.

Dr. Landweber has been studying Oxytricha for two decades and previously uncovered its 16,000 chromosomes. (See related Faculty Q+A and video.)

 

 

Brian Ji_2
Systems Biology Graduate Brian Ji, PhD

For Brian Ji, the big draw to systems biology stemmed from his passion for applying quantitative approaches to understanding biology. While an undergraduate at the University of Wisconsin-Madison, Ji studied nuclear engineering and credits that training for the way in which he tackles scientific questions: creatively, and as a problem solver. 

“There is no one right approach to asking a question and setting out to answer it, and that freedom is what makes science fun for me,” he says. 

Ji studied under Dr. Dennis Vitkup in the Vitkup lab and completed his thesis defense for systems biology in the fall of 2018.  Also an MD student in Columbia’s Vagelos College of Physicians and Surgeons , Ji was attracted to Columbia because of the close interplay between the Systems Biology Department and the Columbia University Irving Medical Center. “Ultimately,” he says, “the opportunity to sit at the intersection between math, biology and medicine was too good to pass up.”

Ji’s PhD work focused on understanding spatiotemporal dynamics of human gut microbiota. He developed several frameworks that leveraged the increasing availability of high-throughput sequencing data to better understand and precisely quantify patterns of human gut microbiota variability across time and space. His work showed that characterizing dynamics—changes in bacterial abundances in our gut—are critical to understanding how these ecosystems function and is highly connected to multiple factors such as host diet, travel and diet. 

Ji also spent part of his PhD studying limitations of cancer cell growth in different environmental conditions. He credits Columbia for exposing him to a variety of research topics. 

Peter Sims, PhD
Peter Sims, PhD

The Mark Foundation for Cancer Research has awarded Peter Sims , PhD, an Emerging Leader Award and will support his work to advance a novel use of single-cell RNA sequencing to develop brain cancer treatments. Dr. Sims, assistant professor of systems biology at Columbia University Irving Medical Center, is one of just eight recipients of the inaugural grant, given to promising early career scientists for projects aimed at substantially unmet needs in cancer risk prediction, prevention, detection and treatment. 

Dr. Sims is an early contributor to the emerging field of large-scale single-cell RNA sequencing, which has made it possible to analyze tens of thousands of cells while simultaneously obtaining imaging and genomic data from each individual cell. He will be using this approach to improve patient-derived models of glioblastoma multiforme (GBM), an aggressive form of cancer that invades the brain, making complete resection difficult. In other words, making it extremely difficult in surgery to remove all cancerous cells from the brain. To date, drug therapies for this type of aggressive brain cancer have had limited success, partly because of the heterogeneity of these tumors. Furthermore,  current patient-derived models for researching glioblastoma do not fully recapitulate the cellular diversity of tumor cells that are present in the tumor, so it is extremely challenging to classify those cells in order to match them with the drug therapies that work. 

Indeed, there is a critical need to better characterize and understand GBM. Dr. Sims has collaborated with several brain tumor experts in the Herbert Irving Comprehensive Cancer Center , including Drs. Peter Canoll, Jeffrey Bruce, Antonio Iavarone and Anna Lasorella to advance single-cell genomic approaches to characterizing this disease. Approaching this problem at the single cell level could result in development of novel treatments that  prioritize and identify the specific drug therapies that may actually work on diminishing these tumor cells. The ultimate goal is to attain better predictions of therapeutic efficacy. 

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