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Research Highlights 2020

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Research Highlights 2020 systemsbiology.columbia.edu Department of Systems Biology Columbia University Irving Medical Center Research Highlights Addressing the Global Pandemic New Tumor-Specific Molecular Interaction Maps 2019-2020 Capture Complexity of Cancer Networks Dynamics of Gut Bacteria Follow Ecological Laws Ancient Part of Immune System May Underpin Severe COVID COLUMBIA UNIVERSITY DEPARTMENT OF SYSTEMS BIOLOGY Table of Contents Inside this issue, learn about the latest research, noteworthy grants and milestones from the Department of Systems Biology. Systems Biology Faculty Address the Global Pandemic Q+A: Raul Rabadan, PhD Find out how several faculty in the department are rapidly As the author of Understanding Coronavirus, Dr. Rabadan has set out to provide readers an accessible overview that quells addressing the novel SARS-CoV-2 virus. ............................Page 3 misinformation about the novel virus, its origin, causes, and spread. Page 10 Systems Biology COVID Volunteers .................................................................................................... During the spring COVID-19 outbreak in New York City, four New Faculty: Mohammed AlQuraishi, PhD members of the systems biology department were especially active in a volunteer effort called Columbia Researchers A warm welcome to Dr. Mohammed AlQuraishi, who Against Coronavirus. ........................................................................Page 4 joined the department as an assistant professor and as a member of Columbia’s Program for Mathematical Genomics. Page 11 New Tumor-Specific Molecular Interaction Maps ................................................................................ Capture Complexity of Cancer Networks Method Detects Genetic Expression Disruptors, Novel representations called SigMaps capture the full Improves Diagnosis of Rare Disease complexity of protein signaling and regulatory pathways in tissue-specific context. ..................................................................Page 5 A new computational method from the lab of Tuuli Lappalainen can identify genes where genetic variants disrupt gene expression in patients and improve the diagnosis of rare Dynamics of Gut Bacteria Follow Ecological Laws genetic disease. .................................................................................Page 12 The gut microbiome is more organized than it first appears and follows some of the same ecological laws that apply to Pew-Stewart Scholar Dr. Xuebing Wu Focuses on birds, fish, tropical rainforests, and even complex economic Therapeutic Targets in Breast Cancer and financial markets. ......................................................................Page 6 Xuebing Wu, PhD, has been selected as a Pew-Stewart Scholar Network-based Approach for Predicting Response for his innovative approaches to cancer research. .....Page 13 to Cancer Treatment Molly Przeworski, PhD, Elected to the National Researchers use algorithm to predict individual patient Academy of Sciences response to inhibition of HDAC6, a master regulator of inflammatory breast cancer. ...................................................Page 7 Congratulations to Molly Przeworski, PhD, elected to the National Academy of Sciences, and recognized for her Gene Signature Predicts Whether Localized distinguished achievements in original research. ...Page 13 Prostate Cancer is Likely to Spread Around the Department Researchers have identified a genetic signature in localized prostate cancer that can predict whether the cancer is Grants, awards, and more. .........................................................Page 14 likely to spread, or metastasize, early in the course of the disease. ........................................................................................Page 8 Newly Tenured Faculty Three new faculty in the Department of Systems Biology Ancient Part of Immune System May Underpin have been awarded tenure and promoted to associate Severe COVID professor. ........................................................................................Page 15 One of the immune system’s oldest branches, called complement, may be influencing the severity of COVID disease. .........................................................................................Page 9 2 systemsbiology.columbia.edu Systems Biology Faculty Address the Global Pandemic study published in Cell Systems, Drs. Sha- pira and Honig applied similar methods to map virus-encoded mimics of host protein structures across thousands of viruses and hosts that are part of Earth’s virome. They identified, among their findings, over 150 human proteins that are mimicked by coro- naviruses, providing clues about cellular processes driving the pathogenesis of the ongoing COVID-19 pandemic. In a study published in Nature Medicine, Dr. Shapira collaborated with Nicholas Tatonetti, PhD, associate professor of systems biology and of biomedical informatics, to leverage these clues in an analytical and computational framework to demonstrate that genetic and Raul Rabadan, PhD, (standing) with Francesco Brundu, postdoctoral research scientist in the functional dysregulation in immune com- Rabadan lab (Credit: Jeffrey Schifman) plement and coagulation pathways are risk factors of morbidity and mortality associat- y early spring, the highly contagious is part of a family of viruses that include ed with COVID-19. Their ongoing efforts Bnovel coronavirus ripped through com- SARS and MERS—two devastating infec- are extending these approaches to identify munities and challenged medical resources, tious diseases that surfaced in the last 20 key genetic and functional determinants of particularly in epicenters like New York years. Xuebing Wu, PhD, assistant profes- disease susceptibility in the context of oth- City. The surge in positive cases at the time sor of systems biology, is an expert in RNA er emerging pathogens. (See related article summoned clinical communities to the front research and studies RNA-centric gene reg- on page 9) lines of the pandemic, and simultaneously ulation in mammalian cells. He is working Andrea Califano, Dr, is a pioneer in the it galvanized the scientific community to on developing a CRISPR-based approach field of systems biology and founding chair quickly collaborate across multiple disci- for killing the SARS-CoV-2 virus, and po- of Columbia’s Department of Systems Bi- plines and problem-solve a cure. tentially also the infected surrounding cells. ology. He has developed sophisticated al- Several faculty in the Department of Sys- CRISPR is a natural bacterial immune gorithms to identify key master regulator tems Biology rapidly came together to ad- system that scientists have begun to use as proteins in tumors and enable the prioriti- dress the novel SARS-CoV-2 virus. There a revolutionary tool to alter genomes. Dr. zation of FDA-approved drugs that could has since been an incredible outpouring of Wu and his collaborators have already de- treat and kill cancer in various tumor types. rapid response by academic researchers to veloped a similar CRISPR-based technique He is now applying these validated meth- aid in a cure or uncover the fundamental bi- to eliminate cancer cells, and intend to apply ods to study the biology of coronaviruses ology driving the novel coronavirus. this method to target COVID-19. The hope and their ability to hijack the machinery of “This is an unprecedented time in history, is that this research can aid in the speedier human host cells. when scientists from all fields who are not development of a therapeutic, not just for Dr. Califano and his collaborators have necessarily experts in virology are forming this novel strain but for future variants of already analyzed gene expression profile teams with exceptional complementary tal- SARS-CoV-2. data generated from SARS-CoV-infected ent to address one of the greatest challenges Data-driven Solutions and mock-infected epithelial cells to iden- our society has ever faced,” said Systems In a study published in Cell, Sagi Shapira, tify the proteins responsible for maintain- Biology Department Chair Andrea Califa- PhD, and Barry Honig, PhD, faculty in the ing the transcriptional state of infection no, Dr. at the time. “The current situation Department of Systems Biology, developed response. (SARS-CoV is closely related creates a unique and unprecedented commit- P-HIPSTer, a computational method that to the current novel coronavirus SARS- ment to a shared goal without institutional, leverages the supercomputing infrastruc- CoV-2 and produces a similar response in geographic, or expertise boundaries.” ture at Columbia to identify key interac- patients.) They’ve applied the computation- A sample of COVID-19 research from tions between all human-infecting viruses al method, OncoTreat, developed by the systems biology faculty: (including coronaviruses) and the cells Califano lab, to identify several promising CRISPR-based Therapeutics they infect. In addition to studying vaccine drugs to potentially treat these infections, Coronavirus genomes comprise sin- design, they are using the information to including drugs used to treat rheumatoid gle-stranded RNA, and the novel coronavi- identify FDA-approved drugs that may be arthritis as well as several kinase and trans- rus, SARS-CoV-2 that leads to COVID-19, repurposed and immediately deployed. In a port protein inhibitors. Dr. Califano and his 3 COLUMBIA UNIVERSITY DEPARTMENT OF SYSTEMS BIOLOGY team have now generated gene expression tise and algorithms to analyze the UK profiles
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