Macie Mattila recently won the Armand Guarino Award for Academic Excellence in Masters Studies. 

Your name, program, thesis title.

Macie Mattila, Master of Science in Cell Systems and Anatomy, “Caspase-2 in Osteoclasts: A Tale of Deletion and Overexpression”

Please tell me about yourself, why did you pick UT Health San Antonio, and your program.

When I was seven years old, I decided that dentistry was for me. I was at the age where most girls were playing princess with their favorite crown, but I found myself only wanting to crown a molar. My early dental dreams cultivated my love for science, and I soon found my perfect little niche in the research lab and in courses that both enlightened and challenged me.

The M.S. in Cell Systems & Anatomy at UT Health San Antonio appealed to me because I wanted to learn anatomy, histology, etc. at the graduate level and complete a research thesis project. As a student in the Anatomical Sciences track, I had the opportunity to perform a full cadaveric dissection and to be a gross anatomy teaching assistant for both first-year medical and dental students. I loved the unique curriculum that this graduate program offered, and now looking back, I believe that my time as a graduate student at UT Health San Antonio has adequately prepared me for the rigors of dental school.

What has been the highlight of graduate school so far? Have you won any awards or have there been any achievements you’ve been proud of?

Aside from meeting my wonderful friends and working with my exceptional mentor, Dr. Rama Sharma, I can say that the highlight of graduate school for me was successfully completing my thesis project. My research experience in college inspired me to continue working at the bench during graduate school. Out of my cohort, I was the only one to choose a benchwork project. I found myself caring for several mouse colonies, culturing osteoclasts, and conducting a myriad of experiments all while learning and teaching anatomy. Finding the perfect balance between research and anatomy was difficult, which is why I consider my greatest achievement to be successfully completing every experiment using two different mouse models and accomplishing all that I intended to investigate with my thesis project.

Please provide a few sentences summarizing your thesis. What was the experience like for you?

Osteoporosis is a silent disease that leads to decreased bone mass resulting in increased bone fragility and incidence of fracture. However, not all genes involved in maintaining bone mass with age have been characterized.

Dr. Sharma’s lab has previously shown that caspase-2, a protein that is involved in mediating cell death, regulates bone homeostasis. Specifically, caspase-2 appeared to play an important role in bone-resorbing cells called osteoclasts. Since those results were observed in mice in which all cells (including bone-forming osteoblasts and bone-maintaining osteocytes) had lost caspase-2 expression, we wanted to confirm that ablating caspase-2 only in osteoclasts led to similar findings. Therefore, we generated conditional null mice in which only mature osteoclasts lacked caspase-2 and conversely, mice that overexpressed caspase-2 only in osteoclasts. I performed several assays using osteoclasts differentiated from these mice, and my results validated a role for caspase-2 specifically in osteoclasts.

Before I even began my thesis work, I knew that it was going to be challenging – but knowing myself, I was confident that I would persevere. I was definitely blessed to have Dr. Sharma as my mentor as well. He worked tirelessly with me on this project, which I was so proud to present on the day of my defense. Overall, my experience was highly rewarding in many ways. Dr. Sharma’s guidance has helped me to evolve into a confident and competent researcher with an extensive repertoire, and I can translate these skills to the field of dental research in the future.

Why are you passionate about your research topic? How did you first become interested in it?

Although I have always loved teeth, I found myself captivated by another mineralized tissue: bone. I am honestly fascinated by the continuous interplay between bone-forming osteoblasts and bone-resorbing osteoclasts, and how bone undergoes remodeling throughout our adult life. I became interested in osteoporosis research after speaking with Dr. Sharma. Osteoporosis is a worldwide health problem that results in more than 2 million fractures every year. Interestingly, osteoporotic fractures are more common than heart attack, breast cancer, and stroke combined! One in three women and one in five men will sustain osteoporotic fractures in their lifetime. Therefore, it is imperative that we identify genes and mechanisms to help fortify our bones as we age.

What’s next?

I will be attending Tufts University School of Dental Medicine to pursue my Doctor of Dental Medicine (D.M.D.) degree with anticipated graduation in 2023.

Any advice for your fellow graduate students?

STAY DETERMINED! In research, things rarely work out on the first attempt, which is why I believe that tenacity is an important quality to have as a graduate student. Take solace in the fact that your work is valuable, and that the entire process will make you a better scientist – focus on the end game!