News

Researchers at the Vagelos College of Physician & Surgeons are rewriting the course of scientific investigation, intent on speeding up the process of discovery that will help patients with cancer, Alzheimer’s disease, diabetes, and other intractable diagnoses.

In cancer, Andrea Califano, Dr, the Clyde and Helen Wu Professor of Chemical and Systems Biology and chair of the Department of Systems Biology, decided to turn cancer treatment theory on its head. The first wave of research in pursuit of personalized oncology focused on clues embedded within individual tumors. Decode the nucleic acids gone awry within the DNA of a particular patient’s cancer, or so the thinking goes, to identify treatments tailored to target that specific mutation.

It’s a fine theory, says Dr. Califano in the article, but investigators still have a lot of work to do before the vast majority of cancers yield to that approach. “Only maybe 25 percent of patients have a mutation that could be defined as actionable,” he says.

For more than a decade, Dr. Califano has championed what might be considered an end run around cancer mutations, focusing instead on identifying and blocking the networks of normal proteins—known as master regulators—hijacked by deranged DNA to spur tumor formation and sustain tumor growth. Prevent the signals those proteins send on behalf of a cancerous mutation, and the cancer itself screeches to a halt.

 

Cory Abate-Shen
Cory Abate-Shen, PhD

Cory Abate-Shen , PhD, who is known for her leading work in the development of innovative mouse models for translational research in prostate and bladder cancers, has been elected a fellow of the American Association for the Advancement of Science (AAAS) . The AAAS is honoring Dr. Abate-Shen for her work in mouse models to better understand how basic cellular mechanisms are co-opted in cancer and for her contributions to the field of cancer biology. 

She joins a class of 416 new fellows, including two additional Columbia University faculty members, Drs. Richard Axel and Upmanu Lall, who also were elected today to the prestigious group. 

Dr. Abate-Shen, the Michael and Stella Chernow Professor of Urologic Sciences at Columbia University Irving Medical Center (CUIMC) , holds joint appointments in the Departments of Systems Biology , Medicine and Pathology & Cell Biology , and is a member and former interim director of the Herbert Irving Comprehensive Cancer Center (HICCC) . 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. Dr. Abate-Shen has been the recipient of numerous awards, including a Sinsheimer Scholar Award, an NSF Young Investigator Award, a Bladder Cancer Advocacy Network Innovator Award and the Women in Cell Biology Junior Award from the American Society for Cell Biology. Currently, she is an American Cancer Society Research Professor, the first to be awarded at CUIMC. 

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.