Department of Systems Biology×

News

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. 

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.”

Sebastien Weyn

Sebastien Weyn, a graduating PhD student in the Chaolin Zhang lab, has been awarded the Titus M. Coan Prize for Excellence in Research. Weyn, who intends to participate in the May 13 Hooding Ceremony at the Vagelos College of Physicians and Surgeons (P&S), is one of two graduates who has received the award, bestowed annually by P&S. Weyn is being recognized in the area of outstanding basic cell and molecular research. 

“I am happy to represent Systems Biology for the award, which together with previous DSB winners, showcase the important biological contributions coming from the department,” says Weyn. “Winning this award also speaks greatly to my mentor, Chaolin, and his vision and insight in the field.”

Work in the Zhang lab concentrates on the study of the nervous system and its underlying molecular mechanisms. The group focuses on the function of post-transcriptional gene regulation, in particular a level of molecular regulation called alternative RNA splicing, in the nervous system.

“The regulation of RNA splicing is surprisingly mysterious despite the fact that it is critical for proper cellular function, and there are several genetic diseases that result from improper splicing,” notes Weyn. “Understanding splicing can lead to breakthrough therapies.” 

For his dissertation project, Weyn dissected the regulatory mechanisms underlying dynamic alternative splicing switches during neurodevelopment. His work led to insights into the role that Rbfox proteins have in promoting mature splicing patterns, including in a number of autism candidate risk genes. The Rbfox family of proteins are important regulators of alternative splicing and mutations of these genes have been linked to several neurodevelopmental disorders. 

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.