Studies underway at Columbia University could change the fate of millions of patients who die every year because existing drugs fail to treat them.
Precision medicine, a new and quickly developing healthcare paradigm, aims to treat diseases using the variability of an individual’s DNA, which influences the body’s production of proteins, nucleic acids and other compounds. This approach revolutionizes how some of the most intractable diseases can be treated, from genetic disorders to the deadliest forms of cancer, the second leading cause of death in America after heart disease.
A number of cancer therapies fail, in part, due to patients’ genetic variability. For example, certain tumors rely on specific proteins for their growth, which the human body produces. And some patients naturally produce less of these tumor-feeding proteins, while others produce more. These individual differences can often dictate why certain drugs work well in some patients, but have little to no effect in others. Understanding patients’ DNA differences will result in treatments tailored to the specific molecular profile of each person, leading to significantly more effective medical care that can save more lives.
As a result of new, interdisciplinary collaborations, researchers in Columbia University’s Faculty of Arts and Sciences are taking steps toward the development of novel medicines that reflect individual patients’ specific genetic needs — and will transform the very nature of health care. The convergence between these different disciplines is one of the key drivers of this new revolution in medicine.
“Precision medicine is an important and rapidly accelerating branch of science that we are investing in at Columbia,” said Peter de Menocal, Dean of Science of the Faculty of Arts and Sciences. “We believe this is the health care approach of the future, and will create next generation medicines.”
Brent Stockwell and Ruben Gonzalez, professors in biological sciences and chemistry who are part of Columbia’s precision medicine initiative, are already working on creating next-generation, DNA-specific drugs. Through a collaborative effort, Stockwell and Gonzalez are actively researching specific compounds that can “neutralize” the proteins that certain cancers need for growth in order to cut off the tumors’ food supply. The two professors are also studying compounds that show promise in treating other diseases, such as neurodegeneration and deadly infections.
Stockwell’s lab group focuses on creating and applying specific biomolecules to live tumor cells. By mapping the molecular profiles of tumors, and their response to drug candidates, Stockwell’s group can predict which patients will benefit from these medicines. The biomolecules that produce the best possible outcomes hold the promise of becoming a mainstream drug one day. Gonzalez’s team uses a state of the art, custom-designed optical microscope to visualize how such candidate biomolecules neutralize the cancer-feeding proteins, rendering them unusable for the tumors.
Gonzalez says that developing the next generation DNA-specific therapeutics requires a full understanding of both humans’ molecular diversity and the molecular dynamics between proteins, tumors, drugs and other possible players.
“We need to see what the molecules are doing so we can understand how differences in a person’s DNA sequence affect this person’s cellular biochemistry,” he said. “Once we have that knowledge, we can design the next generation precision-based medicines for every patient.”
Their research could change the fate of millions of cancer patients who die every year because existing drugs fail to treat them. Precision medicine techniques also show promise in treating Alzheimer’s, Amyotrophic Lateral Sclerosis, muscular dystrophy and other disorders rooted in the patients’ individual genetic biochemistry, which may be corrected with DNA-specific drugs, Stockwell and Gonzalez say.
Together, Stockwell and Gonzalez are creating the Next Generation Precision Medicine Center at Columbia, which will bring together a committed group of researchers to solve the challenges of precision medicine and vastly improve healthcare. Columbia is positioning itself to lead this new field, which lies at the nexus of data sciences, physical sciences, engineering, biology and medicine.
The Center will enable experts from multiple scientific disciplines, such as biology, chemistry, and genetics to pioneer new ideas with cutting-edge equipment in an unparalleled research environment. It is designed to be a hub of intersecting interests where researchers converge on a biological challenge from different perspectives.
The collaborative atmosphere of the Center will facilitate a multidisciplinary approach, which is key to solving complex biochemical puzzles.
“In all places where great science was done, there was a critical nucleus of people, each working in their own research area, but at the same time all working together in a collaborative and synergistic way,” Stockwell said.“Through our research, we want to understand the underlying molecular mechanisms that make drugs’ performance vary between patients, and then explore our ability to target diseases with individual precision,” Gonzalez said. “We believe that this is the future.”
“Through our research, we want to understand the underlying molecular mechanisms that make drugs’ performance vary between patients, and then explore our ability to target diseases with individual precision,” Gonzalez said. “We believe that this is the future.”
— By Lina Zeldovich