Faculty Research Focused on Pediatric Cancers

 

Regina Graham, PhD, is an Associate Professor at the Dr. Kiran C. Patel College of Allopathic Medicine College, as well as an adjunct faculty member in the Department of Chemistry and Physics at the Halmos College of Arts & Sciences.


Please tell us about your experience conducting research on pediatric cancers.

My pediatric cancer research focuses up two types of cancer: brain tumors and neuroblastoma.

Brain tumors are the leading cause of death  in children who have cancer. Sadly, for the children who survive their cancer, less than 50% will be able to live normal independent lives. This is because the cancer treatments the children undergo are severe and can affect the whole body, just like in adults. However, unlike adults, children’s brains and bodies are still developing and the cancer treatments such as radiation and chemotherapy can have a devastating effect on the normal brain and body development.

Therefore, one focus of my research is to develop novel nanomedicines which can directly target and kill the tumors cells while sparing the normal healthy cells. By doing this we can hopefully reduce the devastating side effects of treatment. In the lab we use carbon dots, a relatively new kind of nanoparticle, to deliver drugs across the blood brain barrier.  As the name implies the blood brain barrier is a cellular barrier that regulates what enters the brain from the blood.  This is really important for normal brain function and health but it becomes a major obstacle in the treatment of brain tumors because the blood brain barrier can prevent the chemotherapy from reaching the tumor. Therefore, my lab is using carbon dots which are tiny spherical carbon-based nanoparticles that can be easily created in the lab to cross the blood brain barrier and specifically target tumor cells. The great think about carbon dots is that they can be designed so that they deliver multiple anti-cancer drugs to the tumor instead of just one. This is really important because it will not only allow more cancer cell death but will also help prevent the cancer cells developing drug resistance.

This research has been published in the following:

  • Transferrin conjugated nontoxic carbon dots for doxorubicin delivery to target pediatric brain tumor cells. DOI: 10.1039/c6nr05055g
  • Triple conjugated carbon dots as a nano-drug delivery model for glioblastoma brain tumors. DOI: 10.1039/c8nr08970a
  • Pediatric glioblastoma target-specific efficient delivery of gemcitabine across blood-brain barrier via carbon nitride dots. DOI: 10.1039/d0nr01647k
  • Surface modification of carbon nitride dots by nanoarchitectonics for better drug loading and higher cancer selectivity. DOI: 10.1039/d2nr02063g
  • Carbon Dots in Treatment of Pediatric Brain Tumors: Past, Present and Future Directions. DOI: 10.3390/ijms24119562

The second type of cancer I work on is neuroblastoma. Neuroblastoma, a common pediatric cancer originating from immature nerve cells, primarily affects children under the age of five.  While the outcome for children diagnosed with low grade neuroblastoma is good, the prognosis for children diagnosed with high-grade (stage III and IV) neuroblastoma is especially poor. These tumors can spread to places like the bone marrow, bones, and liver, and they often don’t respond well to usual treatments like chemotherapy, radiation, or surgery. My research on neuroblastoma focuses on targeting tumor cell metabolism. Most cancer cells are highly proliferative including neuroblastoma which requires an increased metabolism to fuel their rapid cell proliferation. We can exploit this high energy requirement by targeting specific metabolic pathways that are increased in neuroblastoma compared to non-cancer cells.

This research has been published in the following:

  • Resveratrol augments ER stress and the cytotoxic effects of glycolytic inhibition in neuroblastoma by downregulating Akt in a mechanism independent of SIRT1. DOI: 10.1038/emm.2015.116
  • NAMPT Inhibition Induces Neuroblastoma Cell Death and Blocks Tumor Growth. DOI: 10.3389/fonc.2022.883318

Advances in precision medicine, including novel drug delivery systems, are critical to improving outcomes for this high-risk population. Therefore, we are exploring the use of carbon dots to treat neuroblastoma.

This research has been published in the following

  • Hydrothermal vs microwave nanoarchitechtonics of carbon dots significantly affects the structure, physicochemical properties, and anti-cancer activity against a specific neuroblastoma cell line. DOI: 10.1016/j.jcis.2022.10.010
  • DFMO Carbon Dots for Treatment of Neuroblastoma and Bioimaging. DOI: 10.1021/acsabm.2c00309

Over the years I have been funded by childhood cancer foundations including the Mystic Force Foundation,  Cancer Free Kids and the Florida Department of Health Live Like Bella Childhood Cancer Foundation. Currently I am funded by a generous grant from HCA Florida University Hospital.

 

What inspired you to pursue research on pediatric cancers?

Growing up, I faced a profound loss when my younger brother passed away from leukemia, a time when treatment options for childhood leukemia were scarce compared to the advances we see today. That experience ignited my lifelong passion for cancer research, a drive I carried into my postdoctoral fellowship at the University of Miami. There, I met Dr. Steven Vanni, a dedicated neurosurgeon whose own son had recently been diagnosed with stage IV neuroblastoma. Motivated by this personal challenge, Dr. Vanni and his wife founded the Mystic Force Foundation to support a pediatric cancer research program. When I was invited to lead this initiative, I embraced the opportunity wholeheartedly, knowing it aligned with my deepest aspirations. This role not only sharpened my focus on pediatric cancers but also strengthened my resolve to make a meaningful impact in this field.

 

Are there any specific challenges that are associated with conducting research on pediatric cancers compared to adult cancers?

Yes, the funding available for pediatric cancer research is significantly less than for adult cancers. Specifically, only about 4% of the National Cancer Institute’s (NCI) budget is allocated to pediatric cancer research. It is sometimes thought that the cancer research done is adults would be translatable to children, but it is just not.

 

Are you collaborating with any other faculty, institutions, organizations, etc. on these research projects?

Yes, I am collaborating with Drs. Roger Leblanc and Eduardo Veliz at the University of Miami, and Drs. Carlos Gonzalez, Reza Razeghifard and Arthur Sikora here at Nova Southeastern University.

 

What opportunities and/or benefits does this research bring to the NSU community (students, faculty, key stakeholders, local population, etc.)?

I have a highly active lab full of volunteer undergraduate, and medical students along with a master’s student enrolled in the M.S. in Medicinal Chemistry program here at Nova .  I make it a focus to get the students involved in all aspects of the research from C-dot synthesis, cell viability studies to identify the optimal drugs to deliver using C-dots to testing of C-dot drug conjugates in pediatric cell lines. In addition, we also do drug discovery research in which we hope to identify novel compounds and new targets for pediatric and adult brain tumors. Students have worked on these projects as well.

 

From left to right: Medical students Emanuella. Emma, Roberto and Matt in the lab.

 

I also make it a goal to help the students prepare for the next steps in their career development. Part of this process is to have the students present their research at local (Nova Southeastern University and other south Florida universities including  FIU, FAU and USF), state (FLASCO) and national conferences (ASBMB).

 

From left to right: Alma, Brianna, Neha, Saya presenting research posters.

 

I am always open to collaborations with Nova faculty. I truly believe science and the development of novel therapies is a team effort. Therefore, to improve the prognosis for children diagnosed with cancer, we need to work together. I look forward to establishing more collaborations with Nova faculty and HCA hospital doctors.

 

How does your research integrate with clinical practice, and are there any recent breakthroughs or promising developments you can share?

Currently my research is at the pre-clinical stage in which we are testing novel nanomedicines to determine functionality which will then be used for pre-clinical safety and efficacy testing in cancer models.


How does your involvement in researching pediatric cancers connect with your other research projects at NSU?

It is all related. I do research on adult brain tumors as well. Both adult and pediatric brain tumors share several of the same treatment obstacles such as the inability for anti-cancer drugs to cross the BBB to reach therapeutic concentrations.

 

How has NSU helped you pursue and/or achieve personal and professional goals you have set for yourself? Any specific NSU resources used?

I have been at NSU for nearly two years now and it has been a great experience. The NSU leadership and community has been very supportive. My lab is located in the CCR and I often make use of the shared facilities.

 

Looking Forward: What is next on the horizon?

The future plans are to further our research on a carbon dot-based drug delivery system with the goal of moving our findings into clinical trial. Part of this requires strong grant funding. So, a major focus of my time is the submission of NIH and DOD grants to help support the research and grow the lab.