Sister Faculty Members Share Dedication to Innovative Research
By David Enders
In her best-selling book, “Sisters,” journalist/author Elizabeth Fishel interviewed hundreds of sisters and discovered the often-intense, often-ambivalent, always-devoted bond between sisters is just as important in their development as their relationship with their mother. In the case of Doctors Nikita and Shivani Ruparel, both accomplished researchers in the Department of Endodontics in the School of Dentistry, sisterhood brings added value to a collaborative department devoted to each other and to discovery.
Nikita “Niki” Ruparel, DDS, PhD, MS, associate professor and director of the Advanced Education Program in Endodontics, uses her experience as a practicing clinician to inform her research in pain pathways, peripheral analgesics, and the role of stem cells in the development of novel analgesics. “For all of my current projects, I literally found the questions in the clinic and tried to answer them in the lab.”
Shivani Ruparel, PhD, MS, associate professor and director of research in endodontics, explores the mechanisms used by cancer cells and peripheral sensory neurons in inducing tumor growth and causing pain in head and neck cancer. “I am interested in understanding how pain is being produced in oral cancer patients and how does the sensory nervous system help in tumor growth and metastasis.”
They come from a long family tradition of medical knowledge and scientific curiosity. Their parents are internal medicine physicians in India operating three clinics, including one attached to their residence, and their extended family boasts 16 doctors. “Discussions of patients with a variety of conditions was always a part of our family conversations,” said Dr. Niki Ruparel, Carlos E. del Rio Chair in Endodontics. It was enough to pique her curiosity in how the human body worked, and why some drugs worked and others did not. After earning a bachelor’s degree in microbiology and a master’s in neurobiology from Mumbai University, “that’s when I started connecting the dots.”
The dots drew a direct line to UT Health San Antonio where she earned her DDS and PhD in cellular and structural biology. After rotating through several neuroscience labs, she found a perfect fit in the pain biology lab of renowned researcher Ken Hargreaves, DDS, PhD, chair of the Department of Endodontics. “What struck me was not only the advanced work in pain, but the family culture and Dr. Hargreaves’ teaching style.”
With opioid overdose deaths up nearly 30 percent in 2020, according to the Centers for Disease Control and Prevention, Dr. Niki Ruparel’s work in peripheral analgesics investigates safer alternatives. “We noticed in endodontic care, even though some patients present with the same radiological evidence of a diseased tooth, about 40 percent of these patients feel no pain.” By comparing pathological tissue from painful and painless patients, Dr. Niki Ruparel explains, differences in molecular pain pathways are identified providing targets for new drugs to turn “off” painful pathways. Her research is also stratified by gender with the relatively recent discovery that females and males do indeed experience pain very differently.
Stem cell research is another promising approach to pain. “There is so much known about the therapeutic nature of stem cells, but very little is known about their potential as pain killers.” She developed a mouse model to study infection-induced pain, including gender differences in pain pathways, for which she was awarded the 2020 Women in Science Award for Distinguished Research. Using stem cells from a dental patient with third molar extractions, she injected the mice with human stem cells and found “they were completely asymptomatic with just one injection, which of course spurred many more questions.” It was discovered that these stem cells were releasing a molecule called Macrophage Migration Inhibitory Factor (MIF) that directly inhibits sensory neurons from processing pain.
Dr. Shivani Ruparel’s career path was influenced by living with a life-threatening chronic health issue since the age of 3. She credits her father with saving her life. “My parents were constantly brainstorming with my doctors to see how my life could be improved. It gave me firsthand experience of what good health care can do and the nobility associated with it.”
Like her sister, she earned her bachelor’s and master’s degrees in microbiology in India, before heading to San Antonio for her PhD in cellular and structural biology. “I learned a great deal about cancer biology through my doctoral training and during my post-doctoral fellowship, I learned more about neuroscience and pain. I realized there was a dramatic dearth in our understanding of how our nervous system really works with cancer. Unlike most cancers, head and neck cancers promote pain at the site early on and, because of that, often lead to opioid dose escalation. There was only one other investigator in the country working on head and neck cancer pain. I wanted to be the next one to significantly contribute to our understanding of the sensory nervous system in head and neck cancer progression and pain,” she said.
Her research targets Brain Derived Neurotrophic Factor (BDNF), and its role in both pain and tumorigenesis (cancer growth). She found that pain is a byproduct of the BDNF produced by cancer cells as they spread. By repurposing existing drugs proven to inhibit BDNF production, she hopes to find one that can effectively treat both pain and tumor growth. Furthermore, her research program also focuses on exploring novel agents that can be potentially used as alternative analgesics to opioids in treating cancer pain.
Dr. Shivani Ruparel takes mentoring just as seriously as her research, receiving the inaugural San Antonio Chapter of the American Association for Dental Research Distinguished Research Mentor Award in 2021. “Mentoring is one of the most challenging aspects of my job and I take it very, very seriously because I know what a good mentor can mean in a student’s life and career. It’s not only about teaching science but giving students the freedom to live up to their creative abilities, fostering collaboration, enhancing leadership skills, and letting them have fun with what they are doing on a daily basis. Research is very difficult if you’re not having fun.”
The Ruparel sisters consider the mentorship of Dr. Hargreaves as crucial in moving their careers in the right direction. “Niki is an accomplished clinician-scientist who has used her clinical insights to generate completely new areas of pain research,” Dr. Hargreaves said. “Simply put, her work is groundbreaking. At the same time, she is a superb educator leading our graduate program in training endodontic residents while mentoring the next generation of clinician-scientists in her lab. Her leadership skills are matched only by her time-management skills! Shivani is an amazing scientist who has combined her PhD training in cancer biology with a post-doctoral fellowship in pain neuroscience. This background is unique and positions her as a rising star in the field of cancer pain.”
The School of Dentistry’s Department of Endodontics consists of more women PhD, DDS/PhD and faculty members than men, but women still make up less than 30 percent of the global research community. The gender gap is closing as long-held bias slowly wanes, assures Dr. Niki Ruparel, but differences in work-life balance and communication styles can be problematic. “There is an unsaid expectation that my body language and speaking style cannot be the same as my male counterparts, and if I do portray that same phenotype, then I will be disliked. As women, this is the tightrope we walk. You need to be masculine enough to be successful, but feminine enough to be likable. And this bias is often perpetuated by other women; the change needs to come from us first, and the key challenge is to start by changing your own perspective.”
Fortunately, the sisters face the challenges together. “We’re soulmates. We really do get along very well, and we bounce ideas off of each other,” said Dr. Niki Ruparel. Her sister agrees. “We are the best of friends and get along professionally and personally. We inspire and learn so much from each other,” added Dr. Shivani Ruparel.