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Yufeng Shen Episcore

The epigenomic profile of RBFOX2, a haploinsufficient gene recently identified as a risk gene of congenital heart disease. Each small box represents 100 bp region around transcription start sites (TSSs) and the shade of the color reflect the strength of the histone mark signal in tissues under normal conditions. RBFOX2 has large expansion of active histone marks (H3K4me3 and H3K9ac), especially in heart and epithelial tissues (purple and gray rows), and tissue-specific suppression mark (H3K27me3) in blood samples.(Credit: Shen lab)

The genetics of developmental disorders, such as congenital heart disease and autism, are highly complex. There are roughly 500 to 1,000 risk genes that can lead to each of these diseases, and to date, only about a few dozen have been identified. Scientists have ramped up efforts to develop computational approaches to address challenges in accurately identifying genetic risk factors in ongoing genetic studies, and the availability of such tools would greatly assist researchers in gaining a deeper understanding of the root causes of these diseases. 

Focusing on haploinsufficiency, a key biological mechanism of genetic risk in developmental disorders, Yufeng Shen , PhD, and his lab have developed a novel computational method that enables researchers to find new risk genes in these diseases. Their key idea is that the expression of haploinsufficient genes must be precisely regulated during normal development, and such regulation can be manifested in distinct patterns of genomic regulatory elements. Using data from the NIH Roadmap Epigenomics Project, they showed there is a strong correlation of certain histone marks and known haploinsufficient genes. Then based on supervised machine learning algorithms, they developed a new method, which they call Episcore , to predict haploinsufficiency from epigenomic data representing a broad range of tissue and cell types. Finally, they demonstrate the utility of Episcore in identification of novel risk variants in studies of congenital heart disease and intellectual disability.  

A research team from Columbia University Irving Medical Center has received a 2018 PCF Challenge Award from the Prostate Cancer Foundation (PCF) to advance prostate cancer research. The interdisciplinary team at Columbia includes leading experts in systems biology, cancer research and medicine from Columbia’s Department of Systems Biology and the Herbert Irving Comprehensive Cancer Center (HICCC)

Announced today, PCF is awarding more than $5.5 million in funding to a total of six teams to conduct research with the highest potential for accelerating new and improved treatments for advanced prostate cancer. PCF is one of the largest non-governmental organizations dedicated solely to funding prostate cancer research, and its annual Challenge Awards are highly coveted in the scientific and medical fields. 

In the United States, prostate cancer is the most common non-skin cancer, and 1 out of every 9 men in the U.S. will be diagnosed with the disease in his lifetime. To date, treatment of the most aggressive forms of prostate cancer represents a clinical challenge. After treatment failure with anti-androgen drugs, which are part of the standard of care for advanced metastatic prostate cancer, only few current therapeutic options remain and the impact on patient survival is limited. Indeed, the field needs major innovative, out-of-the-box approaches to new therapies to combat advanced prostate cancer. 

 

DSB Retreat
Members of the Dennis Vitkup Lab, from l to r: Konstatine Tchourine, German Plata and Jon Chang (Credit: Sandra Squarcia); Photo Gallery of the retreat.

Innovative research projects were highlighted at the Department of Systems Biology’s annual retreat, held October 5, at Wave Hill Public Garden and Cultural Center in Riverdale, NY. The retreat, attended by 160 faculty, staff, post-doctoral scientists, students and guests, also provided an opportunity for young investigators to showcase their work during a poster competition. 

Andrea Califano , Dr., chair of the department, opened the day’s sessions with welcome remarks, as the retreat also served as a site visit by the National Cancer Institute for the Columbia University Center for Cancer Systems Therapeutics (CaST) . CaST, co-directors Drs. Califano and Barry Honig , vice-chair of the department, was established in 2016 as one of the key centers in the NCI’s Cancer Systems Biology Consortium (CSBC). The initiative behind CSBC is heavily grounded on innovation—bringing together interdisciplinary teams of clinical and basic cancer researchers with physical scientists, engineers, mathematicians and computer scientists who collaborate to tackle major questions in cancer biology from a novel out-of-the-box point of view. 

 

Andrea Califano
Andrea Califano, Dr.

Andrea Califano , Dr., a pioneer in the field of systems biology and founding chair of the Department of Systems Biology at Columbia University Irving Medical Center (CUIMC), has been elected to the National Academy of Medicine (NAM) . Membership in the NAM is considered one of the highest honors in the fields of health and medicine and recognizes individuals who have demonstrated outstanding professional achievements and commitment to service.  

A physicist by training, Dr. Califano has taken 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. Directing the conversation about cancer research away from focusing solely on gene mutations, Dr. Califano examines the complex and tumor-specific molecular interaction networks that determine cancer cell behavior. Using information theoretic approaches, analysis of these networks can precisely pinpoint master regulator proteins that are mechanistically responsible for supporting tumorigenesis and for implementing tumor cell homeostasis. Dr. Califano and his lab have shown that master regulators represent critical drivers and tumor dependencies, despite the fact that they are rarely mutated or differentially expressed, thus establishing them as a bona fide new class of therapeutic targets.

October 10, 2018

Q+A with Dr. Laura Landweber

Oxytricha

Oxytricha. (Credit: Bob Hammersmith)

Laura Landweber, PhD, loves a challenge. So it’s no surprise that she has built a scientific career unraveling the hows and whys of a unique single-cell organism known for its biological complexity.  

An evolutionary biologist whose work sits at the interface of genetics and molecular biology, Dr. Landweber, for nearly 20 years, has focused much of her research on Oxytricha trifallax , a microbial organism that is prevalent in ponds, feeds on algae and has a highly complex genome architecture, making it an attractive, albeit challenging, model organism to study. Compared to humans, with 46 chromosomes containing some 25,000 genes, Oxytricha is known to comprise many thousands of chromosomes, in the ballpark of 16,000 tiny “nanochromosomes”. Yet not only is it complex in sheer numbers of chromosomes but the information carried in those individual chromosomes can be scrambled, like information compression, and the process of development in Oxytricha must descramble this information so that it can be converted into RNA and proteins.

“DNA can be flipped and inverted in Oxytricha and the cellular machinery actually knows how to restore order,” says Dr. Landweber. “Hence, it’s this wonderful paragon for understanding genome integrity and the maintenance and establishment of genome integrity.” 

Even more perplexing, in cell division, Oxytricha reproduces asexually when it wants to produce more in number, and it reproduces sexually when it needs to rebuild its genome. It also has the ability to “clean up” its genome, so to speak, eliminating nearly all of the non-coding DNA, or so-called junk DNA. Much of why Oxytricha presents such an intricate genomic landscape remains a mystery, and for Dr. Landweber, the leading expert on this single-celled protist, that wide-open field for potential discovery is what got her hooked. 

composite image of the scientists and research figure
Tuuli Lappalainen (top photo) and Stephane Castel co-led the new study. The hypothesis of the study is illustrated here with an example in which an individual is heterozygous for both a regulatory variant and a pathogenic coding variant. The two possible haplotype configurations would result in either decreased penetrance of the coding variant, if it was on the lower-expressed haplotype, or increased penetrance of the coding variant, if it was on the higher-expressed haplotype. (Composite image courtesy of NYGC)

Researchers at the New York Genome Center (NYGC) and Columbia University's Department of Systems Biology have uncovered a molecular mechanism behind one of biology’s long-standing mysteries: why individuals carrying identical gene mutations for a disease end up having varying severity or symptoms of the disease. In this widely acknowledged but not well understood phenomenon, called variable penetrance, the severity of the effect of disease-causing variants differs among individuals who carry them. 

Reporting in the Aug. 20 issue of Nature Genetics, the researchers provide evidence for modified penetrance, in which genetic variants that regulate gene activity modify the disease risk caused by protein-coding gene variants. The study links modified penetrance to specific diseases at the genome-wide level, which has exciting implications for future prediction of the severity of serious diseases such as cancer and autism spectrum disorder.

NYGC Core Faculty Member and Systems Biology Assistant Professor Dr. Tuuli Lappalainen, PhD, led the study alongside post-doctoral research fellow Dr. Stephane Castel.

Suying Bao, PhD
Suying Bao, PhD

Suying Bao, a postdoctoral research scientist in the Chaolin Zhang lab , has been named an inaugural Precision Medicine Research fellow by Columbia’s Irving Institute of Clinical and Translational Research . The two-year fellowship aims to train postdocs to use genomics and complex clinical data to improve personalized and tailored clinical care and clinical outcomes. 

This fellowship “will provide me with more opportunities to translate my findings from basic science research into clinical application,” says Bao, “and pave my way towards an independent researcher in this field.” 

Bao’s expertise lies in RNA regulation at the interface of systems biology, ranging from the specificity of protein-RNA interaction to function of specific splice variants. RNA regulation is critical in proper cellular function; gaining deeper insights into this complex molecular mechanism will promote the development of precision medicine therapies. 

In this project, Bao is aiming to develop new approaches to identify causal noncoding regulatory variants (RVs) modulating post-transcriptional gene expression regulation, such as RNA splicing and stability.  “A majority of genetic variants associated with human diseases reside in noncoding genomic regions with regulatory roles,” notes Bao. “Thus, elucidating how these noncoding regulatory variants contribute to gene expression variation is a crucial step towards unraveling genotype-phenotype relationships and advancing precision medicine for common and complex diseases.”

To identify these RVs, she will leverage massive datasets of high-throughput profiles of gene expression and protein-RNA interactions generated from large cohorts of normal and disease human tissues and cell lines by multiple consortia, such as ENCODE, GTEx and CommonMind, and develop innovative computational methods of data mining. 

Hyundai $2.5M Grant to Columbia
Julia Glade Bender, MD, (center) at the Hyundai Hope on Wheels announcement Mar. 29 during the New York International Auto Show at the Jacob Javitz Center. (Photo courtesy of HHOW)

A team of researchers at Columbia University Irving Medical Center (CUIMC) has recently been awarded a five-year $2.5 million grant from Hyundai Hope on Wheels (HHOW) to fund innovative pediatric cancer research. 

The team at Columbia is being led by principal investigator (PI), Julia Glade Bender , MD, associate professor of pediatrics at CUIMC, with co-PIs Andrea Califano , Dr, chair of Columbia’s Department of Systems Biology and Darrell Yamashiro , MD, PhD, director of pediatric hematology, oncology and stem cell transplantation, along with researchers from Memorial Sloan Kettering, University of San Francisco Children’s and Dana-Farber Cancer Center. 

The Quantum Collaboration award from HHOW is aimed at funding research focused on childhood cancers with poor prognosis. At Columbia, the team will target osteosarcoma, the most commonly diagnosed bone tumor in children and adolescents. No new treatment approaches have successfully been introduced for osteosarcoma in nearly 40 years, and patients with the disease have not benefited from recent breakthroughs like immunotherapy or DNA sequencing and require a shift in the understanding and approach to therapy. 

Califano-Cancer Bottleneck
The N of 1 trial leverages systems biology techniques to analyze genomic information from a patient’s tumor. The goal is to identify key genes, called master regulators (green circles), which, while not mutated, are necessary for cancer cell survival. Master regulators are aberrantly activated by patient-specific mutations (X symbols) in driver genes (yellow circles), which are mutated in large cancer cohorts. Passenger mutations (blue circles) that are not upstream of master regulators have no effect on the tumor. (Image: Courtesy of the Califano Lab)

A novel N of 1 clinical trial led by the Califano Lab at Columbia University Irving Medical Center is focusing on rare or untreatable malignancies that have progressed on multiple lines of therapy, with the goal of identifying and providing more effective, customized therapies for patients. The approach is grounded in a computational platform developed over the last 14 years by the Califano Lab to allow accurate identification of a novel class of proteins that represent critical tumor vulnerabilities and of the drug or drug combination that can most effectively disarm these proteins, thus killing the tumor. Platform predictions are then validated in direct tumor transplants in mice, also known as Patient-Derived Xenografts (PDX). 

“We call these proteins master regulators and have developed innovative methodologies that allow their discovery on an individual patient basis,” said Dr. Andrea Califano , Clyde and Helen Wu Professor of Chemical and Systems Biology and chair of the Department of Systems Biology at Columbia. 

Project GENIE
Richard Carvajal (left) and Raul Rabadan are lead PIs on Project GENIE

Columbia University Irving Medical Center (CUIMC) has recently joined 11 new institutions to collaborate on Project GENIE, an ambitious consortium organized by the  American Association for Cancer Research . An international cancer registry built through data sharing,  Project GENIE , which stands for Genomics Evidence Neoplasia Information Exchange, brings together leading institutions in cancer research and treatment in order to provide the statistical power needed to improve clinical decision-making, particularly in the case of rare cancers and rare genetic variants in common cancers. Additionally, the registry, established in 2016, is powering novel clinical and translational research. In its first two years, Project GENIE has been able to accumulate and make public more than 39,000 cancer genomic records, de-identified to maintain patient privacy. 

Judith in the lab
Judith Kribelbauer

As a child growing up in a small town in Germany, Judith Kribelbauer excelled in science, counting chemistry and mathematics as her two favorite subjects from grade school through high school. After high school graduation, she attended the Ruprecht-Karls University in Heidelberg to pursue a bachelor’s degree in chemistry, which she completed in 2012. 

Becoming more serious about pursuing scientific research, Kribelbauer, who is graduating this May with a PhD in the Systems Biology Integrated Program, moved to the U.S. to work as a graduate exchange student at the University of North Carolina-Chapel Hill (UNC) before enrolling at Columbia University in 2013. At UNC, using SHAPE-MaP sequencing technology, she researched the structural basis of the HIV-1 RNA frame-shift element, a sequence that causes ribosomes to shift reading frames, therefore producing truncated proteins.  

Columbia’s collaborative environment—the chance to work with researchers spanning areas from biology to chemistry and physics to computer science—is what drew her to the University and ultimately to concentrating in systems biology. 

“Thanks to this unique environment, I could realize my dream research project—combining both experimental and computational approaches,” says Kribelbauer. “This comprehensive training allowed me to conduct my thesis research in two labs, with both PhD advisers having appointments in Systems Biology.”

May 7, 2018

From Code to Cure

Columbia Magazine

Published Spring 2018 cover story , Columbia Magazine

As reported by David J. Craig, senior editor at Columbia Magazine , we are living in the age of big data, and with every link we click, every message we send, and every movement we make, we generate torrents of information. In the past two years, the world has produced more than 90 percent of all the digital data that has ever been created. New technologies churn out an estimated 2.5 quintillion bytes per day. 

Today, researchers at Columbia University Irving Medical Center (CUIMC) are using the power of data to identify previously unrecognized drug side effects; they are predicting outbreaks of infectious diseases by monitoring Google search queries and social-media activity; and they are developing novel cancer treatments by using predictive analytics to model the internal dynamics of diseased cells. These ambitious projects, many of which involve large interdisciplinary teams of computer scientists, engineers, statisticians, and physicians, represent the future of academic research.

Craig covers Dr. Nicholas Tatonetti's work involving prescription drug safety and his innovative use of digital health and clinical records and Dr. Andrea Califano's unconventional computational approaches in advancing cancer research.

To read the full article , visit the online issue of Columbia Magazine

Raul Rabadan
Raul Rabadan

Systems Biology Professor Raul Rabadan, Phd , has been awarded a Philip A. Sharp Innovation in Collaboration award from Stand Up to Cancer (SU2C) , a group established by film and media leaders to fund cancer research projects that have the potential to quickly deliver new therapies to patients. Dr. Rabadan has received the award jointly with collaborator Dan A. Landau, MD, PhD, of Weill Cornell Medicine.

A theoretical physicist whose expertise lies in the cross section of mathematical genomics, tumor evolution, and cancer research, Dr. Rabadan will work together with Dr. Landau on their winning project, “Cupid-seq—high throughput transcriptomic spatial mapping of immune-tumor interactions in the micro-environment.”  The investigators will devise a novel sequencing technique and computational method for better understanding immune recognition mechanism in glioblastoma. Dr. Rabadan is currently a principal investigator on the SU2C-National Science Foundation Drug Combination Convergence Team and Dr. Lau is a 2016 recipient of a SU2C Innovative Research Grant.

The idea behind the Sharp Awards is to fund projects that involved SU2C researchers who have not yet worked together, including collaborations between members of Dream Teams, Research Teams, and Convergence teams, and between SU2C members and recipients of its innovative research grants. The latter are typically early-career investigators. The Sharp Awards are named after Sharp, Nobel laureate and institute professor at MIT and the Koch Institute for Integrated Cancer Research, to honor the emphasis he has placed on the importance of collaborative research. 

Dr. Rabadan, who also is professor of biomedical informatics at Columbia University, is one of 10 recipients of this year’s Sharp Awards; investigators hail from the U.S., Canada, and the Netherlands, and projects are being funded from a pool of $1.25 million. 

Andrea Califano
Andrea Califano, Dr, chair of Columbia's Department of Systems Biology

The Chan Zuckerberg Initiative (CZI) has awarded Andrea Califano, Dr, a new grant in support of his work to develop a comprehensive library of regulatory interactions within molecularly defined cellular populations and molecular determinants (master regulators) of individual cells’ state. This will arm scientists with a unique resource to study biology at the individual cell level and to gain further insight into the fundamental understanding of molecularly distinct cell types.

With the support of CZI, founded by Facebook CEO Mark Zuckerberg and his wife, Priscilla Chan, Dr. Califano, chair of Columbia’s Department of Systems Biology, and his group will apply their computational methods that accurately and systematically measure and analyze regulatory interaction at the single cell level to elucidate distinct cellular states and to establish both cell-state markers, as well as the proteins that are causally responsible for implementing that state. 

A critical advantage offered by the approaches that the Califano Lab brings to the CZI community is that of addressing one of the most critical issues in single cell biology characterization. Specifically, since the depth of transcriptional sequencing of single cells is generally a very small fraction of what can be achieved from bulk tissue, most of the genes are actually lost and only the 20% to 30% of the genes that are most highly expressed can be detected. This has been dubbed the gene dropout problem. By using the recently published metaVIPER algorithm, this problem is eliminated as regulatory networks are used to accurately infer the activity of 6,000 proteins that include all the critical players in cell state implementation and modulation, even if their RNA cannot be detected, thus fully addressing gene dropout and allowing much deeper investigation of single cell biology. 

Coauthors
Study lead coauthors Nathan Johns (left), systems biology graduate student in the Wang Lab, and Antonio Gomes, former member of the Wang Lab, now at Memorial Sloan Kettering Cancer Center.

Advances in synthetic biology have already spurred innovation in the areas of drug development, chemical production and health diagnostics. To help push the field even further, and potentially at a more rapid pace, a new, comprehensive resource devised by Columbia University investigators will help synthetic biologists better engineer designs for complex biological systems.

A team of researchers, led by Harris Wang, PhD, assistant professor of systems biology and of pathology and cell biology, report the characterization and analysis of thousands of bacterial regulatory elements in different species of bacteria. The paper , published March 19, appears in Nature Methods .

Synthetic biology employs well-characterized genetic parts to assemble gene circuits with specific functions, such as producing chemicals or sensing the environment. The toolbox of genetic parts to make functioning genetic circuits, however, has been limiting. A key shortfall is the availability of precisely measured regulatory sequences-segments of DNA responsible for dialing up or dialing down the expression of proteins within an organism. For many commercially useful bacteria, tuning gene expression has been challenging because of a lack of reliable regulatory sequences. 

"Synthetic biology is now at a precipice where we are not just demonstrating proof-of-concept in the laboratory but we're moving toward real-world applications," says Nathan Johns , lead coauthor of the paper, a member of the Wang Lab and a graduate student in the Department of Systems Biology at Columbia. "To facilitate this, having a wide array of useful genetic components and measurement techniques-in our case, regulatory sequences-are extremely helpful." 

Feb 7-8 Cancer Genomics Symposium

Pictured above, Adolfo Ferrando (left), professor of pediatrics and of pathology and cell biology at Columbia, with Luis Arnes, associate research scientist and first-place winner of the symposium's poster competition; For photos from the symposium, visit the gallery page . Credit: Lydia Lee Photography

A multidisciplinary team of researchers across Columbia University have been busy addressing the complex challenges in basic and translational cancer research. Faculty and investigators are bridging their expertise in fields ranging from mathematics, biology, and engineering to physics, genomics, and chemistry to develop innovative approaches to better understand, for instance, cancer disease progression, drug resistance, and the systems-wide network of tumor evolution.

Central to this ongoing work is research grounded in cancer genomics and mathematical data analysis explored during a two-day conference Feb. 7-8 co-hosted by the National Cancer Institute (NCI) centers at Columbia University Medical Center, Cornell University, and Memorial Sloan Kettering Cancer Center. (Visit the Rabadan Lab YouTube Channel for video of the symposium).

"Genomics is becoming an important tool for the quantitative study of biological systems,” says Raul Rabadan, PhD , professor of systems biology at Columbia and director of the Center for Topology of Cancer Evolution and Heterogeneity and of the Program for Mathematical Genomics . “This meeting organized by four different NCI centers addressed some of the important challenges and new perspectives on the quantitative understanding of cancer using genomics tools.”

Two new precision medicine tests, born out of research from the Califano Lab, that look beyond cancer genes to identify novel therapeutic targets have just received New York State Department of Health approval and are now available to both oncologists and cancer researchers for use at the front lines of patient care. As reported by Columbia University Irving Medical Center (CUIMC), the tests are based on research conducted by CUIMC investigators—and could pave the way for a more precise approach to cancer therapy and help find effective drugs when conventional approaches to precision medicine have failed.

“This means that the vast majority of cancer patients who do not have actionable mutations, or have not responded to, or have relapsed after chemotherapy or targeted therapy, now have access to additional tests that can help their oncologist select the treatment best suited to their specific tumor,” says the tests’ lead developer, Andrea Califano, Dr., chair of systems biology at Columbia University Vagelos College of Physicians and Surgeons.

The two tests, DarwinOncoTreat and DarwinOncoTarget, are available exclusively through the Laboratory of Personalized Genomic Medicine in the Department of Pathology and Cell Biology at Columbia University Vagelos College of Physicians and Surgeons. The tests were developed by DarwinHealth, a Manhattan-based biotech firm founded in 2015 by Dr. Califano and colleague, Gideon Bosker, MD.

For the complete article, visit the CUIMC Newsroom.

Courtesy of The Olive Lab

Shown here, a human pancreatic tumor stained with Masson's trichrome; Image credit: Dr. Kenneth Olive

The Lustgarten Foundation has awarded Columbia University’s Herbert Irving Comprehensive Cancer Center (HICCC) a three-year grant, as part of its Translational Clinical Program, to test a new precision medicine approach to the treatment of metastatic pancreatic cancer.

“The prevailing model in personalized cancer treatment is to attack the DNA mutations that are believed to be driving an individual patient’s tumor,” says principal investigator Kenneth P. Olive, PhD , assistant professor of medicine and pathology & cell biology at HICCC. “While this approach has been astonishingly effective for a handful of rare cancers, we expect it will only work for a very small fraction of patients with the most common types of cancer.”

Pancreatic ductal carcinoma (PDA)—the most common form of pancreatic cancer—is a case in point. Researchers have identified few genetic drivers in pancreatic tumors, and the most common driver ( KRAS ) is not easily targeted. Conservatively, only about 15 percent of PDA patients are likely to benefit from conventional DNA mutation-based precision medicine therapies and most of these will either not respond or will relapse with a drug-resistant form of the disease.

“Our study takes an entirely new approach,” says Dr. Olive. “Instead of looking at the mutations encoded in a tumor’s DNA, we analyze the tumor’s RNA. Since RNA is the tissue-specific ‘working copy’ of a cancer cell’s DNA, it’s a more accurate reflection of the genetic programs that are active in a tumor and critical for its survival. We can then match the patient to approved and investigational drugs that inhibit those programs.”

Nicholas P. Tatonetti, PhD, has recently been named director of clinical informatics at the Institute for Genomic Medicine (IGM) at Columbia University Medical Center. In this new role, he is charged with planning, organizing, directing and evaluating all clinical informatics efforts across the Institute. In particular, he will focus on the integration of electronic health record data for use in genetics and genomics studies.

Dr. Tatonetti, who is Herbert Irving Assistant Professor of Biomedical informatics with an interdisciplinary appointment in the Department of Systems Biology, specializes in advancing the application of data science in biology and health science. Researchers in his lab integrate their medical observations with systems and chemical biology models to not only explain drug effects, but also further understanding of basic biology and human disease. They focus also on integration of high throughput data capture technologies, such as next-generation genome and transcriptome sequencing, metabolomics, and proteomics, with the electronic medical record to study the complex interplay between genetics, environment, and disease.

At the Institute for Genomic Medicine, researchers are focused on innovative approaches to genomic medicine. Their multi-tiered approach to genomic medicine utilizes large scale genomic sequencing and analysis, paired with functional biology to advance the diagnosis, characterization, and treatment of genetic diseases. IGM is playing a critical role in Columbia’s overall Precision Medicine Initiative, a major University-wide effort to provide medical diagnosis, prevention and treatment based on an individual’s variation in genes, environment, and lifestyle. 

Dr. Tatonetti, who joined Columbia in 2012, is also affiliated with the Center for Computational Biology and Bioinformatics, the Department of Medicine, the Department of Biomedical Informatics, and the Center for Cancer Systems Therapeutics.

Broad, Columbia collaborators
Three of the investigators in new Columbia, Broad Institute research collaboration aimed at gastric and esophageal cancer; L to R: Dr. Andrea Califano, Dr. Cory Johannessen, and Dr. Adam Bass (Johannessen image: Martin Adolfsson; Bass image: Sam Ogden/Dana-Farber Cancer Institute)

A research collaboration underway between Columbia’s Department of Systems Biology, the Broad Institute of MIT and Harvard, and Columbia University Medical Center (CUMC) is working to accelerate the discovery of new cancer drug combinations targeted at gastric and esophageal cancer. These tumors have not yet attracted prominent research focus and attention, and yet the general outcome for patients with these diseases is poor. According to the American Cancer Society, survival rates are only 20% at five years after diagnosis.

The newly formed research alliance between research teams at Columbia and at the Broad Institute came about thanks to a four-year gift by the Price Family Foundation, known for its philanthropic support of education, health, and biomedical research.

The Columbia-Broad team includes Dr. Andrea Califano , cofounder and chair of the Department of Systems Biology; Dr. Adam Bass , associate member of the Broad Institute; Dr. Cory Johannessen, senior research scientist at the Broad Institute; Dr. Josh Sonnett , the director of The Price Family Center for Comprehensive Chest Care, Lung and Esophageal Center at Columbia; and Dr. Naiyer A. Rizvi , the Price Chair in Clinical Translational Research at Columbia.

In 2016, the Price Family Foundation suggested that a team of scientists at the Broad Institute meet with researchers from CUMC. At the time, the Foundation was eager to leverage the project at the Broad—where researchers had uncovered an interesting finding for gastric and esophageal cancer—with innovative cancer systems biology work it was supporting at CUMC, focusing on the same diseases.

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