Scholar of the Month

I have been interested in genetics and DNA repair since undergraduate school when I did work with Drosophila (fruit flies) as an undergraduate at DePauw University and then my studies on DNA repair and mutagenesis in graduate school. I continued in this field during my postdoc at Rockefeller as an ACS fellow where I learned molecular biology which was just taking off and took a project with me to my first academic position, still working in fruit flies. There we started working on a specific DNA repair protein APE1, and from that point when I moved to IUSM we continued the work. A few years later it was determined that the APE1 protein has another major function called redox signaling (and received the parallel name Ref-1). We have been working on both functions of this protein as potential targets for therapeutics in cancer and more recently in retinal and inflammatory bowel disease. I have now been working on this target for over 30 years.

The APE1/Ref-1 protein is elevated in numerous pediatric and adult cancers and other diseases impacting multiple important pathways which are involved in the cancer, metastasis and disease progression. APX3330, a clinical drug we have developed, as well as new second generation compounds that we are developing, block the ability of Ref-1 to turn on downstream genes involved in cancer growth. Keeping these genes turned down, or off, results in the blockage of the pathways that are driving the cancer and other diseases we have been studying.

In short, we are developing molecules to be used in a variety of cancers along with retinal disease, inflammatory bowel disease such as Crohn’s and Ulcerative Colitis and necrotizing enterocolitis (NEC) which impacts neonates.

Our research has advanced a lead molecule to clinical trials, a phase 1 trial in oncology and a phase 2 trial in diabetic retinopathy/ diabetic macular edema. This occurred through the licensing of our drugs from IUSM to Apexian Pharmaceuticals, my co-founded company, and also to Ocuphire Pharma. We are currently in the process of developing a new program out of Apexian to advance our new molecules to use in inflammatory bowel disease as an oral tablet. The implications in any of these areas are significant and will provide new options for people with these health issues. We are particularly excited about our new direction in IBD as there are minimal oral drugs available for this disease and our approach is unique in the target being addressed by our molecules.

In addition to the IBD studies, we are working with collaborators on the use of our drugs for necrotizing enterocolitis (NEC), a devastating neonatal surgical emergency caused by an upregulation of oxidative stressors that leads to inflammation and bowel injury in neonates. There are no currently approved treatments for NEC. Our recent preclinical data demonstrates a potential use of Ref-1 inhibitors, showing a reduction of inflammation and bowel injuries.

Collaborating with investigators locally and globally in the various areas we are focusing on such as cancer, IBD, NEC and retinal diseases is a lot of fun. I get to learn different areas of science with the potential to make a difference in multiple areas of clinical need. I also get to work with students from undergraduates, graduate to postdoctoral fellows which is always fun and exciting. Mentoring has always been rewarding to me as those that come after us are the future.

I like to travel with my wife and spend time with our kids. I also like to spend time doing “work” as a hobby especially spending time developing our drugs to move them to the clinic using my company as well as licensing our work to other companies so they can advance to the clinic as quickly as possible.

Students are intimately involved in our research. We have undergraduate students involved in the research during the year and also as interns in the summer through a number of summer programs at IUSM and IUSCCC. We have graduate students, both PhD and MD/PhD, working on our projects. Additionally, we have postdoctoral fellows who join our lab to gain more training and career advancement for their next steps into the workforce whether it be academic or industry.

We include community members in a number of programs I am involved with the IUSCCC. The community members are involved in advisory panels, aid in review of pilot funding and help keep us alerted to the needs of people in the community. They are a very important part of keeping us grounded in our research.

We are continuing our studies of APE1/Ref-1 in cancer, particularly pancreatic cancer as well as pediatric sarcomas. We are also looking to do some studies in colon cancer and we have a collaboration with a colleague at IU-ND in gastric cancer.  In these studies, as we gain more information on the target protein and its multiple roles, we are developing new small molecules to be used clinically.

We are also continuing to develop the use of our molecules in inflammatory bowel disease (IBD) and necrotizing enterocolitis.

Our immediate efforts are to form a company that can conduct clinical trials in IBD to rapidly advance a novel treatment to the people that desperately need them.