Jingyue Ju
Personalized Medicine
Human Genome Decoder

Deep inside a single cell is the genome, the DNA repository containing instructions for the development and function of all living organisms. Those DNA instructions in a human genome are comparable to a string of three billion genetic letters in a unique language. Deciphering this biological lexicon holds potential for understanding how and why disease affects people; how genes work together to direct the growth, development, and maintenance of an entire organism; and more about gene regulation.

Genomics may as well be considered the extreme sport of the scientific world. It’s a rigorous, complex, and demanding discipline that requires researchers to have a natural fascination for decoding the function of humanity’s blueprint, an ability to integrate different areas of science and engineering, and a desire for the adrenaline rush that comes with discovering new knowledge about what makes each human unique.

“Intense effort and interest go hand in hand in using molecular science and engineering to pursue genomic research,” says Jingyue Ju, the Samuel Ruben–Peter G. Viele Professor of Engineering, professor of chemical engineering and pharmacology, and director of the Center for Genome Technology & Biomolecular Engineering at Columbia. “The rewards are that there is an almost daily advancement of this science, which fuels our excitement for inventing new molecular engineering approaches to investigate the genetic and molecular mechanisms underlying health disorders in order to maintain a healthy life.”

Leveraging his expertise in molecular science and engineering, Ju and his team are developing revolutionary technologies to dramatically reduce the cost of DNA sequencing so that each person’s genome can be routinely decoded on a credit card-sized chip for just $1,000. Dramatically reducing the cost of DNA sequencing could mean that, soon, sequencing an individual’s genome could become a routine part of medical research and health care.

Four-color DNA sequencing by synthesis data using four cleavable fluorescent nucleotide reversible terminators on a DNA chip.

Ju co-invented the fluorescence energy transfer labeling technology for DNA sequencing that was widely used to successfully complete the international Human Genome Project. The Ju Laboratory at Columbia, along with its collaborators, invented several generations of new DNA sequencing technologies, which include the development of a four-color DNA sequencing-by-synthesis platform using cleavable fluorescent nucleotide reversible terminators, currently the dominant approach used in next-generation DNA sequencing systems. What really intrigues scientists like Ju is constantly inventing new approaches for deciphering the entire genome sequence efficiently and cost-effectively, a proposition that requires a great deal of expertise from different areas of science and engineering, along with substantial funding for long-term research.

“This comprehensive project is great fun, because we create new ideas from the vast knowledge of various areas of science and engineering,” Ju says. “The initiative creates a wonderful learning environment for myself and for my students.”

Antibiotics for the Masses
Elmer L. Gaden
Alumnus and Former Faculty

A true Columbia institution, Elmer L. Gaden (1924–2012) began his remarkable career in biochemical engineering as a student, logging long hours at Havemeyer Hall, ultimately earning a BS in 1944, an MS in 1947, and a PhD in 1949, all from the Engineering School. He returned to campus to join the faculty after a year at Pfizer.

Gaden’s pioneering thesis explored what concentration of oxygen enables penicillin to ferment, grow, and multiply most rapidly, setting the stage for mass production of a wide range of antibiotics and a new epoch for medicine. With a passion for harnessing biological processes to serve human needs, Gaden published widely and founded the research journal Biotechnology and Bioengineering, which he edited for more than two decades. In 1988 he received the Founders Award from the American Institute of Chemical Engineers and, in 2009, was honored with the prestigious Fritz J. and Dolores H. Russ Prize for his foundational research.

During 25 years on the Columbia Engineering faculty, the Brooklyn-born Gaden was a beloved teacher, researcher, mentor, and friend. He founded the School’s program in biochemical engineering, served as chair of the Department of Chemical Engineering, and earned Columbia’s Great Teacher award. In 1974, the same year he won admission to the National Academy of Engineering, Gaden left Morningside Heights to become dean of the College of Engineering, Mathematics and Business Administration at the University of Vermont. He concluded his career at the University of Virginia, retiring in 1994, but always nurtured a warm relationship with his alma mater.

Gaden received Columbia Engineering’s Egleston Medal in 1986. He died in 2012, at the age of 88, but his spirit lives on in the Elmer L. Gaden Lectureship. Founded by the Department of Chemical Engineering in 2007, the annual series hosts leading researchers and scientists who uphold Gaden’s legacy of innovation and excellence.

The Ju Laboratory is currently collaborating with Genia Technologies Inc.,—researchers at Harvard University and the National Institute of Standards and Technology (NIST) to develop a nanoporebased sequencing by synthesis (NanoSBS) system that will accelerate the use of DNA sequencing for wide applications in clinical diagnosis and health care. This collaboration, supported by a $5.25 million grant from the National Institutes of Health, focuses on the research and development of a single-molecule electronic NanoSBS platform combining three technological advancements: NanoTag sequencing chemistry developed in a collaboration between the laboratories of Ju at Columbia and Dr. John Kasianowicz at NIST; Genia’s metal-oxide semiconductor integrated circuit; and the novel protein constructs from Professor George Church’s laboratory at Harvard Medical School. Genia has licensed the NanoSBS technology, and the resulting singlemolecule electronic DNA sequencer is expected to be faster, more accurate and cost-effective than current commercially available technologies in decoding the human genome. Recently, Roche, a leader in research-focused health care with combined strengths in pharmaceuticals and diagnostics, acquired Genia for $125 million in up-front payment, plus up to $225 million in milestone payments. With the collaborative strength of the leaders in biotechnology and the pharmaceutical industries, the team’s goal is to develop a leading platform for personalized medicine.

Because each human differs from every other human by millions of variations in their genomes, understanding each person’s genomic blueprint could provide vital information for disease prediction and prevention, while treatment could be tailored to the individual’s genome. The key to this amazing big-picture potential for personalized medicine is continued research at the molecular level to discover genetic networks and cellular functions, coupled with bioinformatics and computational biology. That’s exactly where Ju is happy and excited to be working: “My colleagues and I are inspired to harness our efforts and interdisciplinary expertise to produce new technologies for human health,” he says.

—by Amy Biemiller