By Sarah Paris

The match of dentistry and precision medicine may not seem intuitive, but there is more synergy in their engagement than meets the eye. 

At this year’s Precision Medicine World Conference (PMWC), two UCSF faculty from the School of Dentistry presented work that stradles the spectrum of precision medicine research. Ophir Klein, MD, PhD, professor and chief of the Divisions of Medical Genetics and Craniofacial Anomalies, discussed how the power of stem cells can be harnessed to treat human disease. On the clinical end, Michael Reddy, DMD, DMSc, the dean of UCSF’s School of Dentistry, focused on the possible connection between inflammation of the gums and an epigenetic risk for preterm birth. 

It is widely known that pregnant women tend to have more inflammation of the gums. What Reddy investigated in two recent studies was the possibility of a two-way street: that the inflammation in turn might influence pregnancy outcomes. He conducted a multicenter study of women at high risk, who were supplied with “smart” toothbrushes and given dental hygiene instructions, along with regular reminders. The study showed a significant reducation in preterm births.

These findings, according to Reddy, raise the question whether the mechanism behind the improved outcome is genetic, epigenetic, or strictly a result of the social intervention. Was there a transmittable, biological disease that affected pregnancy? 

Part of Reddy’s interest in attending PMWC 2020 was to find potential collaborators with a high level of technological expertise to dig deeper into the precise mechanism of the inflammation. This investigation would include using samples of oral microbiome, blood, umbilical cord, and placenta to search for genes that are activated or inactivated. Other analysis might include bacteria, as well as inflammatory mediators, along with social determinants of health. Could a precision medicine approach lead to a targeted intervention?

“Going into the meeting, my hope was to find partners, given that there are world experts in this area attending PMWC. I am just contributing this one component – oral health – that has been left out and may be significant. But to solve the whole puzzle will require experts from many areas, including data science experts,” said Reddy.

The conference brought together experts from across the globe representing academic health care as well as industry leaders in diagnoses and therapeutics. There was no shortage of potential alliances. "It was a great to establish new connections across UCSF and learn more about the breadth and depth of what our health and science faculty are doing to lead the way in developing the field of precision medicine. The chance to make connections that will allow oral health to move from a broad-based public health approach to precise data-driven interventions is an exciting frontier for UCSF Dentistry." 

Dentistry as a Collection Point for Whole Genome Sequencing

Just as Reddy is interested in partnering with precision medicine experts, they are interested in partnering with him. "Some of the most prominent early geneticists were dentists," said Aleksandar Rajkovic, MD, PhD, the Chief Genomics Officer at UCSF.  And ambulatory dental clinics may be an ideal location to access potential participants for genetic studies. "Dentists see a relatively healthy population. This is a great opportunity to recruit people and collect samples for a broad study, such as our UCSF Whole Genome Sequencing (WGS) population sequencing and return of results pilot," Rajkovic notes. "The UCSF School of Dentistry can lead the way in population genetics."

"It's a natural fit," adds Reddy. "Dentists have long term relationships with their patients, and the collection of saliva for genomics can be easily added to the workflow."

Using dental clinics as collection points could open the way for gathering other data. In recent years, a multitude of diseases have been linked to imbalances in the microbial ecology of the human body, spurring the creation of a new UCSF Benioff Center for Microbiome Medicine, which includes faculty from the School of Dentistry. 

Reddy hopes that, along with saliva for the WGS pilot, they might be able to collect oral microbiome samples and add them to the database. “Once we have that information, we can start generating hypotheses based on the data along with the clinical findings. Are there changes in the microflora that predict diseases? There may be subtle shifts you can see by looking at the bacteria and the host that might predict certain outcomes. Ultimately, this could lead to dentistry as a community screening tool.”

A Dentist, a Doctor, a Nurse, and a Pharmacist Walk into a Lab

As a health-focused campus, UCSF is uniquely positioned for collaborations among researchers in the Schools of Medicine, Dentistry, Pharmacy, and Nursing. The professional schools also benefit from the data experts and computing powerhouses on campus, especially the UCSF Bakar Computational Health Sciences Institute, a central element of the UCSF Precision Medicine platform.

To faciliate the exchange of information, the School of Dentistry is implementing the EPIC electronic health record system. “On the most basic level, it will allow everyone access to a complete medical record, including a patient’s oral health history that might contribute to their medical condition. These vital linkages are essential to precision medicine,” said Reddy.

Dean Reddy is excited to become part of the precision medicine matrix at UCSF. "The next step for me is to to engage additional UCSF Dentistry faculty and harness their talents and abilities to help us lead dentistry into a more digital and data-driven future. I am convinced that our patients will benefit greatly from these collaborations.”