Precision medicine is personal—especially for Matt Might, Ph.D., director of the Hugh Kaul Precision Medicine Institute at UAB.

The new approach to care brought help for his son, born with an ultra-rare disease. Now Might is leading UAB in world-changing research. Through precision medicine, the discovery of a mutation in a single gene could unlock doors to new treatments and cures. A series of investments—more than $17 million—is helping UAB find new options for hard-to-treat illnesses.

All over campus, transformative gifts to the Campaign for UAB have brought to life the campaign’s theme, “give something, change everything.” With more than 98,000 donors pledging more than $840 million as part of UAB’s largest-ever philanthropic campaign, programs from the arts and humanities to the basic sciences have been impacted.

One series of investments—more than $17 million given through the Campaign for UAB toward a promising new field known as precision medicine—is set to transform medicine not only in Birmingham but across the country and around the world.

Those are bold words, but Matt Might, Ph.D., has the evidence to back them up. Might, a member of President Obama’s White House Precision Medicine Initiative, arrived in Birmingham this summer as the inaugural director of the Hugh Kaul Precision Medicine Institute at UAB. Precision medicine has already brought help and hope for his son, Bertrand, who was born with an ultra-rare disease. The Mights spent years traveling to medical clinics in search of a diagnosis. Matt Might was a researcher focused exclusively on computer science until his son’s painful odyssey led him to discover the principles of precision medicine—and use them to help identify Bertrand’s disorder: NGLY1 deficiency.

He didn’t stop there; Might’s efforts have now located more than 50 other patients around the planet with the same disease and jump-started an aggressive search for new treatments and an ultimate cure. (Learn more about Might’s incredible journey in this story) “I’m convinced we can do the same thing for many others here at UAB,” Might says.

Breaking through Barriers

What exactly is precision medicine? There are many different definitions, “but it ultimately comes down to getting the right drug, to the right patient, at the right time,” Might says. Another way of saying the same thing, he adds, is: “ultra-individualized care beyond the boundaries of what we can do today.”

Might came to Alabama to stretch those boundaries. He was drawn by the $7 million investment from the Hugh Kaul Foundation in the Precision Medicine Institute, which will allow him to recruit a core of world-leading researchers to UAB.

Then there are the specialized facilities already available here: the high-throughput screening machines at UAB-affiliate Southern Research Institute, which can automatically sift through millions of compounds to find new treatments; the Alabama Drug Discovery Alliance, a UAB-Southern Research partnership (funded in part by a $2 million gift from Protective Life/Dai-Ichi and a $500,000 gift from McWane, Inc.) that accelerates the path of potential new drugs from UAB labs to the marketplace; and the presence of experts on the UAB faculty in key areas of basic science and clinical care, such as Bruce Korf, M.D ., Ph.D., Chief Genomics Officer for UAB Medicine and leader of UAB’s renowned Undiagnosed Diseases Program.

Might has a vision for the future of medicine. “We have reached the end of the era of ‘not actionable,” he says. “There will be no patient who comes through our doors who we tell, ‘There is nothing we can do.”

Winning the Race

To see Might’s vision in action, step over to the Comprehensive Cancer Center, which is leading the way in “precision oncology.” Once a month, clinicians and scientists from across UAB gather to analyze difficult cases with the Molecular Tumor Board. The group is led by Eddy Yang, M.D., Ph.D., ROAR Southeast Cancer Foundation Endowed Chair in Radiation Oncology, professor and vice chair for translational science in the Department of Radiation Oncology and deputy director of the UAB Precision Medicine Institute and its associate director for precision oncology. Yang and his colleagues review the records of patients who are not responding to the traditional therapies for their cancer type. Appropriate cases are sent out for genetic sequencing, at no cost to patients, to determine if there are any other options available.

One of these patients, Yang recalls, had salivary gland cancer, and had run out of treatment options. But the DNA sequencing identified an intriguing clue: the patient’s tumor had a mutation commonly seen in melanoma, a form of skin cancer. That suggested a new treatment option, which brought the patient remission for more than a year.

“Sequencing isn’t a magical cure at this point,” Yang pointed out recently in UAB Medicine Magazine. “We’re not going to find drugs for every person whose tumor we sequence, but we may be able to offer better treatment options for some patients.”

The good news is that drug development is happening at such a rapid pace that a few extra months can make a big difference. “Because of the furious drug development that’s occurring, sometimes what we’re trying to do is buy patients enough time to get to the next treatment,” Yang says. “We have patients for whom we found an actionable mutation that we treated before immunotherapies were approved, and we were able to bridge them to the point where immunotherapy became approved.”

Accelerating New Treatments

Those new therapies may well be developed at UAB. Yang, who is both a clinician and a scientist with his own lab doing basic research in cancer, notes that, with increased competitiveness for research funding worldwide, philanthropy plays a major role in keeping promising work alive. “The funding climates right now are horrible,” he says. “What philanthropic efforts have allowed us to do is keep moving — generating the pilot data that enables us to go and make a much stronger application for grant funding, and making sure that our labs are not at a standstill. Because of philanthropy, we can take on more risk—high-risk, high-reward studies that NIH and other funding agencies don’t like to fund right away without pilot data.”

Endowments such as Yang’s own ROAR Southeast endowed chair, “help protect my time,” says Yang. “Rather than being in clinic all the time, it allows me to focus on some of these research efforts.” (There have been 90 endowed faculty positions created so far as part of the Campaign for UAB.)

Much of Yang’s translational work in his lab is funded through philanthropy, he notes. “These types of funding have allowed me to perform research that has now led to clinical trials. I have two ongoing in breast cancer and one in head and neck cancer, looking at new combinations of targeted treatments.”

Philanthropic funding from AutoTec, a privately held company in Birmingham, has helped accelerate breast cancer research from basic science studies in Yang’s lab toward a promising new treatment. Yang’s team discovered a molecule known as a microRNA that blocks a protein called PARP, which is crucial to the survival of cancer cells. "It really slows down cancer,” Yang says. “We were able to publish that data because of Autotec’s support, and we’ve now generated some models that make me more confident that we can move forward with developing strategies to deliver this molecule.” The investment from Autotec has also resulted in new grants from the Breast Cancer Research Foundation of Alabama to help support the work, Yang notes.

“This research takes a lot of resources,” says Yang. “The technology is expensive and it changes very rapidly. The analysis is difficult and the drugs themselves are very expensive. A lot of philanthropic support is needed to make these advances.”