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. 

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.”

Erin Bush with Department of Systems Biology Assistant Professor Peter Sims and College of Physicians & Sciences Dean Lee Goldman. (Photo: Amelia Panico)

The Department of Systems Biology is proud to congratulate Erin Bush on being selected for the Columbia University College of Physicians & Surgeons 2016 Officer of Research Award. The award is one of six given annually to recognize select staff members for their outstanding contributions in the workplace. Recipients of the 2016 were recognized in a ceremony that took place at Columbia University Medical Center on January 12, 2017.

Erin is a staff associate in the JP Sulzberger Columbia Genome Center and a sequencing specialist working in the laboratories of Peter Sims and Andrea Califano. She has been helping to develop new next-generation sequencing techniques, focusing on low input and single cell DNA and RNA library preparation and testing. As the CUMC Newsroom reports:

Clinical and molecular data are currently stored in many different databases using different semantics and different formats. A new project called DeepLink aims to develop a framework that would make it possible to compare and analyze data across platforms not originally intended to intersect. (Image courtesy of Nicholas Tatonetti.)

Medical doctors and basic biological scientists tend to speak about human health in different languages. Whereas doctors in the clinic focus on phenomena such as symptoms, drug effects, and treatment outcomes, basic scientists often concentrate on activity at the molecular and cellular levels such as genetic alterations, gene expression changes, or protein profiles. Although these various layers are all related physiologically, there is no standard terminology or framework for storing and organizing the different kinds of data that describe them, making it difficult for scientists to systematically integrate and analyze data across different biological scales. Being able to do so, many investigators now believe, could provide a more efficient and comprehensive way to understand and fight disease.

A new project recently launched by Nicholas Tatonetti (Assistant Professor in the Columbia University Departments of Systems Biology and Biomedical Informatics) along with co-principal investigators Chunhua Weng (Department of Biomedical Informatics) and Michel Dumontier (Stanford University), aims to bridge this divide. With the support of a $1.1 million grant from the National Center for Advancing Translational Science (NCATS) the scientists have begun to develop a tool they call DeepLink, a data translator that will integrate health-related findings at multiple scales.

As Dr. Tatonetti explains, “We want to close what we call the interoperability gap, a fundamental difference in the language and semantics used to describe the models and knowledge between the clinical and molecular domains. Our goal is to develop a scalable electronic architecture for integrating the enormous multiscale knowledge that is now available.”

Each year, participants in the ISCB/RECOMB Conference on Regulatory and Systems Genomics select publications over the past year that they consider to have made the most significant contributions to the field. During the most recent conference, held in Philadelphia on November 15-18, 2015, the top 10 papers were announced. Among those selected were four involving Columbia University Department of Systems Biology investigators. 

Andrea Califano, the Clyde and Helen Wu Professor of Chemical Systems Biology and Chair of the Columbia University Department of Systems Biology, has been named a recipient of a National Cancer Institute Outstanding Investigator Award. The seven-year grant will support the development of systematic approaches for identifying the molecular factors that lead to cancer progression and to the emergence of drug resistance at the single-cell level. 

Oliver Hobert

Oliver Hobert, an interdisciplinary faculty member of the Department of Systems Biology, has received a Javits Neuroscience Investigator Award from the National Institute of Neurological Disorders and Stroke (NINDS). This prestigious grant provides long-term support for investigators who have demonstrated exceptional achievement throughout their careers. The award will enable the Hobert Lab to pursue a new project investigating sex-based differences in the regulation of neuronal identity.

Also a Professor of Biochemistry and Molecular Biophysics and an Investigator of the Howard Hughes Medical Institute, Dr. Hobert is known for his research using C. elegans to understand the molecular programs that control cell-type differentiation within the nervous system. C. elegans has become an invaluable model organism for studying the nervous system because it contains just over 300 neurons whose development has been studied in great detail.

A grant from the Office of Naval Research will support the development of three foundational synthetic biology technologies for engineering the human gut microbiota.

Harris Wang, an assistant professor in the Columbia University Department of Systems Biology, has been selected for the Office of Naval Research 2015 Young Investigators Program. This highly selective program promotes the development of early-career academic scientists whose research shows exceptional promise and creativity. With the support of this award, Dr. Wang will extend his research in the field of synthetic biology to develop new technologies for engineering the gut microbiome, the ecosystem of bacteria that inhabit the human digestive system. These new methods, Wang anticipates, could provide new ways of designing communities of different microbial species and ultimately modulating interactions between the gut, the immune system, and the brain.

Andrea Califano and Aris Floratos will lead an effort to reclassify tumors catalogued in TCGA according to their master regulators.

Andrea Califano and Aris Floratos, faculty members in the Columbia University Department of Systems Biology, have received a two-year, $624,236 subcontract to develop a new classification system of cancer subtypes. The agreement was awarded through a subcontract from Leidos Biomedical Research, Inc., which operates the Frederick National Laboratory for Cancer Research for the federal government.  

By performing an integrative analysis of genomic data from the Cancer Genome Atlas (TCGA) and proteomic data from the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), the researchers plan to recategorize tumors collected in TCGA based on the master regulator genes that determine their state. This is in contrast to other approaches based on expression of genes that reflect tissue lineage and proliferative processes. In addition, the team will link the genetics of each tumor sample to the specific master regulators that determine its state using a recently published novel algorithm (DIGGIT). Ultimately, the project aims to provide a more useful catalog of pan-cancer subtypes that could help to identify biomarkers and therapeutic targets for specific kinds of tumors, and ultimately provide a resource to guide the next generation of precision medicine.

“We have to reevaluate the way in which we organize tumors within subtypes, using both gene expression data and mutational data,” says Dr. Califano. “Right now the common approach is to classify tumor types based on rather generic genes that are differentially expressed between subtypes. But most of these genes play no role in actually driving the disease. We want to shift the emphasis and classify tumors based on the genes that truly regulate tumor state and survival.”