Science Spotlight with Dr. Cruz-Monserrate

A key aspect of your research program is to develop strategies for the detection, prevention, and treatment of pancreatic cancer, particularly the most common type of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC).  Why is PDAC so difficult to detect early on?

One of the main reasons is related to basic human anatomy. The pancreas is located deep inside the body, making it hard for doctors to feel it and detect any abnormalities. Moreover, there are no clinical diagnostics available for the early detection of PDAC. There are some imaging modalities that could be utilized in people who are at an increased risk for the disease, but this disease is usually diagnosed when it is at a late stage of the disease as some symptoms tend to be vague and related to multiple other causes. 

Through your research, what have you identified as the risk factors for developing PDAC?

One of the risk factors for PDAC that my laboratory studies is obesity. Despite the strong association between obesity and PDAC development, the underlying mechanisms via which obesity is a risk factor remain unclear. The adipose tissue can secrete many factors from its various cell types and tissue compartments that are linked to tumor growth. Currently, it is unclear which cell type secretes factors and among those factors which can molecularly contribute to the risk of PDAC in obese individuals. Our long-term goals are to identify the molecular mechanisms by which adipose tissue affects the tumor microenvironment (TME) that promote PDAC, and to develop strategies to identify those obese individuals at risk of developing PDAC.

What innovative methodology are you using in your research?

We take various approaches to our research, among those are using genetically engineered mouse models that recapitulate the progression of human PDAC and apply multiple type of obesity related interventions to study obesity-associated PDAC prevention. Using those, in addition, to novel genomics tools such as 10X genomics, we study this disease at the cellular level. Specifically we study the adipose microenvironment which is a novel approach that distinguishes our laboratory from others. The research in my laboratory also relies on vital access to a rich repository of tissues collected over more than a decade at OSU. We champion and maintain a tissue biorepository of PDAC sample from patients that have consented to our studies, which allows us and other OSU researchers to translate study results from the lab to clinical models. We at OSU have one of the few pancreatic diseases’ biorepositories intended to study metabolic disorders like obesity in PDAC.

What are the challenges related to this type of research?

Sometimes what works in the preclinical models does not translate into the clinical setting. Therefore, utilizing multiple preclinical models is the ideal way to confirm our hypotheses and using human samples or human clinical data is key to validating them prior to executing clinical trials. In my research I also have the patients’ needs in mind as we navigate the molecular mechanisms of the biological processes we study. 

February is National Cancer Prevention Month.  Are you investigating any specific dietary interventions as preventative measures for developing PDAC? 

Yes, we are looking at various ways to manage obesity via intentional weight loss, related to increased physical activity and dietary modulations such as those related to modulating dietary fats in the diets. One such diet is the popular ketogenic diet.

Who are your primary collaborators?

I have multiple clinical and basic science collaborators that have made my research program grow and successful. Among those are Drs Phil Hart, Somashekar Krishna, Tom Mace, Mary Dillhoff, Martha Belury, Lei Cao, Susan Knoblaugh, Stacey Culp, Jiangjiang Zhu, Christopher Coss, Maria Mihaylova, Andy Gunderson among many more.

Any closing thoughts?

I work closely with physician-scientists to bring research from the lab to patients. I truly believe in team science and the power of collaboration to build collaborative projects while leveraging expertise from multiple areas to solve difficult problems.