Family Tragedy Drives Susan Mallery, ’81 DDS, ’90 PhD, To Research Breakthroughs

FAMILY TRAGEDY DRIVES SUSAN R. MALLERY, ’81 DDS, ’90 PHD, TO RESEARCH BREAKTHROUGHS

While Dr. Susan R. Mallery was a dental student at Ohio State, she lost her father to small cell carcinoma of the lung, her sister to Hodgkin lymphoma and another sister to an aggressive form of lupus. “I was horribly depressed,” she recalls. “My little nephews had lost their mothers, and I remember thinking, ‘My sisters were doing really wonderful things. This is so unfair.”

Driven forward by the losses in her family and her “hatred of cancer,” Dr. Mallery — now chair of the Division of Oral and Maxillofacial Pathology at the College of Dentistry — has built a prolific research career on the prevention and treatment of oral cancer. After completing her DDS at Ohio State, she practiced dentistry for over a year before her longtime calling toward pathology led her to complete a National Institutes of Health (NIH) research fellowship at Georgetown University. She returned to Ohio State for specialty training in oral pathology, bolstered by a five-year NIH Dental Scientist Award that enabled her to complete her clinical training, earn a PhD in Medical Biochemistry, defend her dissertation concurrently and earn Diplomate status in her specialty.

The focus of her dissertation — biochemical modulators of cell cycle progression to the DNA synthesis “commitment” phase — became the roadmap for her research trajectory that continues to bear fruit today. As a College of Dentistry faculty member since 1990 and a member of the Molecular Carcinogenesis and Chemoprevention Program at Ohio State’s Comprehensive Cancer Center, Dr. Mallery is in the midst of two multimillion R01 awards from NCI/NIH, one of which is a human clinical trial for patients with precancerous oral lesions.

Along with a University of Michigan pharmaceutical chemist colleague, Steve Schwendeman, PhD, Dr. Mallery developed a chemopreventive patch to provide local delivery of fenretinide, a synthetic retinoid derived from vitamin A. Developed by Johnson & Johnson in 1978, fenretinide was designed to re-direct precancerous cells toward regulated, normal growth. “This particular drug was a bench-top chemopreventive rock star,” says Dr. Mallery. “The chemists who designed it knew what they were doing. People thought it was going to be the answer to curing cancer.”

Similar to many chemopreventives, fenretinide’s major challenge is its bioavailability. In pill form, the majority of fenretinide is inactivated during passage through the liver. And in large doses, it causes side effects like impaired night vision, dry skin and mouth, and hyperlipidemia. Fenretinide is also hydrophobic and insoluble in water — presenting unique challenges when delivered in the mouth.

Dr. Mallery worked with Dr. Schwendeman to “take this extremely water-insoluble drug and develop a way to keep it active in a saliva-rich environment, penetrate the surface keratin gain access to the target basal layer cells.” She identified a clinical trial collaborator, ARx Pharma, to develop the final clinical formulation to be used in clinical trials. ARx’s technical and scientific expertise have resulted in marked patch improvements including enhanced patient comfort and ability for large scale patch production. The team is finishing preclinical animal studies and acquiring the data necessary for submission of an Investigational New Drug (IND) application to the Food and Drug Administration (FDA). Once the IND is in hand, the project will submit an application to the Institutional Review Board (IRB), the final

This project has been “years in the making,” notes Dr. Mallery, who is always anticipating the design of her next project. Previously, Dr. Mallery in conjunction with the college’s Oral Surgery faculty, conducted two clinical trials involving a black raspberry gel, which proved to be very effective for one-third of patients. The lessons learned from those projects—and the desire to broaden the positive impact—were the basis for the development of the new patch.

Next up? Dr. Mallery and her colleagues want to address a downside of the new patch: It only treats pre-cancerous lesions that can be seen. “Many people who smoke or drink or have specific genetic diseases are prone to developing incipient, not yet clinically visible precancerous lesions throughout the mouth.” A recently patented, patch-complementary formulation, developed in coordination with Joerg Lahann PhD, University of Michigan Biomedical Engineering, will deliver chemopreventive-releasing nanoparticles for field coverage throughout the mouth. In parallel studies, Dr. Mallery’s lab is investigating fenretinide’s mechanisms of cancer-prevention. “Our results show the fenretinide patch is safe and provides cancer preventing effects. What remains to be determined is how such a small molecule can deliver such pervasive growth regulatory effects. Data and publications that clearly elucidate fenretinide’s mechanisms of action are essential to support the validity of the project as well as our IND, in in the event of clinical success, a New Drug Application to the FDA.”

Beyond research, Dr. Mallery is a College of Dentistry faculty member. She participates in dental hygiene and predoctoral clinical and didactic teaching and is a strong advocate for the unique experiences provided by clinical education. She directs a D4 clinical pathology correlations course that empowers students to apply their knowledge in an active learning environment. “I designed a course I would have wanted as a dental student,” says Dr. Mallery, who has been chosen as Student Government Didactic Teaching Award recipient and a Convocation Hooder more than 30 times. “It means a lot to me. I regard our dental students as our colleagues in training and that’s how I treat them.” She’s also humble about her 2007 induction into Ohio State’s Athletic Hall of Fame in honor of her exceptional undergraduate cross-country and track career, crediting the athletic genes passed along from her parents in addition to her internal motivation.

Motivation has been an important force in Dr. Mallery’s life, propelling her forward as an exemplary athlete, researcher, faculty member and more. “My strategy through my life has been to flip the negative. If you encounter adversity, flip that energy into something that’s positive,” she says. “That’s just how I’m wired; action over passivity any day.”