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Cory Abate-Shen, PhD, a distinguished scientist whose multidisciplinary research has advanced our understanding of the molecular basis of cancer initiation and progression, has been named chair of the Department of Pharmacology at Columbia University Vagelos College of Physicians and Surgeons. Her appointment will be effective April 1, 2019.

Recruited to Columbia in 2007, Dr. Abate-Shen is currently the Michael and Stella Chernow Professor of Urologic Sciences and professor of pathology & cell biology, medicine, and systems biology. She has served as the leader of the prostate program, associate director, and twice as interim director of the Herbert Irving Comprehensive Cancer Center (HICCC) at Columbia University Irving Medical Center and NewYork-Presbyterian.

An internationally recognized leader in genitourinary malignancies, Dr. Abate-Shen is particularly interested in advancing our understanding of the mechanisms and modeling of prostate and bladder tumors. An innovator in the generation of novel mouse models for these cancers, her work has led to the discovery of new biomarkers for early detection, as well as key advances in cancer prevention and treatment.

In the fall of 2018, Dr. Abate-Shen was elected a fellow of the American Association for the Advancement of Science (AAAS). She is an American Cancer Society Professor, the first faculty member at Columbia University Vagelos College of Physicians and Surgeons to have received this honor. Previously, she served as a member of the National Cancer Institute’s Board of Scientific Counselors, and she currently is a member of the board of directors of the American Association of Cancer Research. 

Dr. Abate-Shen will succeed Robert S. Kass, PhD, the Hosack Professor of Pharmacology, Alumni Professor of Pharmacology, and chair of pharmacology since 1995.

Visit the CUIMC Newsroom for the full announcement

Master regulators of tumor homeostasis

In this rendering, master regulators of tumor homeostasis (white) integrate upstream genetic and epigenetic events (yellow) and regulate downstream genes (purple) responsible for implementing cancer programs such as proliferation and migration. CaST aims to develop systematic methods for identifying drugs capable of disrupting master regulator activity.

The Columbia University Department of Systems Biology has been named one of four inaugural centers in the National Cancer Institute’s (NCI) new Cancer Systems Biology Consortium. This five-year grant will support the creation of the Center for Cancer Systems Therapeutics (CaST), a collaborative research center that will investigate the general principles and functional mechanisms that enable malignant tumors to grow, evade treatment, induce disease progression, and develop drug resistance. Using this knowledge, the Center aims to identify new cancer treatments that target master regulators of tumor homeostasis.

CaST will build on previous accomplishments in the Department of Systems Biology and its Center for Multiscale Analysis of Genomic and Cellular Networks (MAGNet), which developed several key systems biology methods for characterizing the complex molecular machinery underlying cancer. At the same time, however, the new center constitutes a step forward, as it aims to move beyond a static understanding of cancer biology toward a time-dependent framework that can account for the dynamic, ever-changing nature of the disease. This more nuanced understanding could eventually enable scientists to better predict how individual tumors will change over time and in response to treatment.

Chimpanzee

By using statistical methods to compare genomic data across species, such as chimpanzees and humans, the Przeworski Lab is gaining insights into the origins of genetic variation and adaptation. (Photo: Common chimpanzee at the Leipzig Zoo. Thomas Lersch, Wikimedia Commons.)

Launched approximately 100 years ago, population genetics is a subfield within evolutionary biology that seeks to explain how processes such as mutation, natural selection, and random genetic drift lead to genetic variation within and between species. Population genetics was originally born from the convergence of Mendelian genetics and biostatistics, but with the recent availability of genome sequencing data and high-performance computing technologies, it has bloomed into a mature computational science that is providing increasingly high-resolution models of the processes that drive evolution.

Molly Przeworski, a professor in the Columbia University Departments of Biological Sciences and Systems Biology, majored in mathematics at Princeton before beginning her PhD in evolutionary biology at the University of Chicago in the mid-1990s. While there, she realized that the availability of increasingly large data sets was changing population genetics, and has since been interested in using statistical approaches to investigate questions such as how genetic variation drives adaptation and why mutation rate and recombination rate differ among species. In the following interview, she describes how population genetics is itself evolving, as well as some of her laboratory’s contributions to the field.

Oliver Hobert
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.

Recently, electron microscopy was used to compare nervous systems in male and hermaphrodite worms, and showed that some of these neurons are present in both sexes. Interestingly, the researchers discovered that even when these neurons had the same lineage history, position, morphology, and molecular features, there was a striking divergence in the patterns of synapse formation between the sexes. Under the new grant, the Hobert Lab will attempt to identify the mechanisms that control this divergence. The project should produce not only a much deeper understanding of sex-based differences in neuronal identity, but also new resources that will support future investigation of this phenomenon.

Winners of the Javits Neuroscience Investigator Awards are nominated by NINDS staff members and members of the National Advisory Neurological Disorders and Stoke Council (NANDS). The grant acknowledges grant recipients as being leaders in neuroscience who have been highly productive or have contributed paradigm-shifting ideas. By supporting investigators for 4-7 years, the grant also anticipates high productivity in the years to come. 

Comparing human and mouse prostate cancer networks

Computational synergy analysis depicting FOXM1 and CENPF regulons from the human (left) and mouse (right) interactomes showing shared and nonshared targets. Red corresponds to overexpressed targets and blue to underexpressed targets.

Two genes work together to drive the most lethal forms of prostate cancer, according to new research by investigators in the Columbia University Department of Systems Biology.  These findings could lead to a diagnostic test for identifying those tumors likely to become aggressive and to the development of novel combination therapy for the disease.

The two genes—FOXM1 and CENPF—had been previously implicated in cancer, but none of the prior studies suggested that they might work synergistically to cause the most aggressive form of prostate cancer. The study was published today in the online issue of Cancer Cell.

“Individually, neither gene is significant in terms of its contribution to prostate cancer,” said co-senior author Andrea Califano, the Clyde and Helen Wu Professor of Chemical Biology in Biomedical Informatics and Chair of the Department of Systems Biology. “But when both genes are turned on, they work together synergistically to activate pathways associated with the most aggressive form of the disease.”

Co-principal investigator Andrea Califano discusses the new study.

“Ultimately, we expect this finding to allow doctors to identify patients with the most aggressive prostate cancer so that they can get the most effective treatments,” said co-senior author Cory Abate-Shen, the Michael and Stella Chernow Professor of Urologic Sciences and also a member of the Department of Systems Biology. “Having biomarkers that predict which patients will respond to specific drugs will hopefully provide a more personalized way to treat cancer.”

The cell-of-origin model in cancer biology suggests that some tumors are more aggressive than others because of differences in the cell lineages from which they arise. In the prostate gland, there are three types of epithelial stem cell — luminal cells, basal cells, and rare neuroendocrine cells. There has been some discrepancy in the scientific literature, however, about whether luminal cells, basal cells, or both can act as a cell of tumor origin.

In a paper published online in the journal Nature Cell Biology, researchers in the laboratories of Columbia University Department of Systems Biology members Michael Shen, Andrea Califano, and Cory Abate-Shen undertook a comprehensive analysis of prostate basal cell properties in mouse models. They used a technique called genetic linkage marking to study an identical cell population in multiple assays of stem cell function.

The studies showed that discrepancies in the published literature arise because basal stem cell properties can change when studied outside their endogenous tissue microenvironment; that is, in ex vivo cell culture and tissue grafting assays. To avoid this problem, they suggest, genetic lineage tracing in vivo should be considered the gold standard for identifying physiologically relevant stem cells.