CoBRE Junior Investigator: Philippe Diaz

Image of Dr. Philippe Diaz

Simply stated, Dr. Philippe Diaz’s research focus is drug discovery. Dr. Diaz’s approach is based on the design and development of small molecules modulating multiple targets or inhibiting the degradation of endogenous molecules exhibiting polypharmacology. Polypharmacology is the action of a molecule on multiple targets or disease pathways. A polypharmacological approach aims to understand and optimize the unknown biological activities for existing small molecules such as cannabinoids or retinoic acid. Dr. Diaz believes that drugs with multiple targets provide a superior therapeutic effect compared to ligands with a single target in the treatment of complex diseases and disorders, such as pain or itching. Dr. Diaz’s research combines medicinal chemistry, molecular biology, and RNA sequencing to characterize and identify synergies and overlaps between biological pathways modulated by small molecules.

After Dr. Diaz completed his military service, he landed a fellowship from the French government to support his doctoral work. The unique Ph.D. program enables students to complete their research project in the industry. Before he defended his thesis, Dr. Diaz was hired as a team leader in medicinal chemistry. He describes this point in his career as being a little bit challenging, but exciting due to the competing demands of his thesis and leading the MedChem team. He learned a lot in industry since his molecules were screened not only for their biological activities but also for their drug-like properties. After a couple of years, Dr. Diaz was promoted to head of the Parallel Chemistry Department where they were using automation to synthesize molecules and then project leader where he oversaw the full monitoring of a project in addition to the medicinal chemistry from research to early development. With this function, Dr. Diaz had to source active compounds for clinical studies and to understand not only research but also development. Since Dr. Diaz never had the opportunity to do a postdoc, nonetheless had a desire to be more connected with doctors and patients, the Diaz’s decided to move to Houston, TX, where he set up a research lab for an anesthesiologist at the MD Anderson Cancer Center.

As is the case with most Montana transplants, Houston didn't fit the Diaz family’s expectations. In 2008, they decided to make the move to Missoula where Dr. Diaz was tasked with the management of a Medicinal Chemistry Core Facility founded by Chuck Thompson and supported by a P30 National Institute of Neurological Disorders and Stroke (NINDS) grant. Dr. Thompson was Dr. Diaz’s mentor and helped him to understand funding mechanisms and improve his grantsmanship. Dr. Diaz notes that Dr. Thompson was a key player in their decision to stay in Missoula. In 2013, with Dr. Fanny Astruc-Diaz, they decided to start a drug discovery company called DermaXon.

Through DermaXon, the couple set out to translate their academic lab discoveries to development and commercialization. The couple received several small grants from the Montana Department of Commerce and the Michael J. Fox Foundation for Parkinson Research to assist them in getting started. Shortly after that, the couple received two STTR Phase 1 awards and more recently an SBIR Phase 2 award. The SBIR Phase 2 award will allow them to start regulatory studies required for human clinical studies. The project aims to develop a new small molecule to treat the skin disorders associated with different forms of congenital ichthyosis. They signed a licensing agreement option with the University of Washington to license the patent protecting the compounds of this phase 2 award. The patent protecting the compounds synthesized in his academic lab and screened by Dr. Isoherranen at the University of Washington is co-owned by the University of Montana. A Canadian pharmaceutical company has licensed another one of Dr. Diaz's patents targeting Glioblastoma with a different technology. Those patents could be future sources of revenue.

Dr. Diaz notes that holding the role of CoBRE Junior Investigator for the last three years has helped improve his academic research skills. Even though he has demonstrated success with Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) grants, writing an NIH R01 or R15 is different. Essentially, STTR/SBIR function around milestones whereas R01, R21 or R15 are built on hypotheses; which is still a little challenging for Dr. Diaz’s industry lens. Through participation in the Hot Water Workshop, Dr. Diaz had the opportunity to gather feedback from established and successful academic researchers. Furthermore, his project supported by the CoBRE empowered him to focus on the fundamental science aspects of his research and to develop organotypic models of non-healthy skin with which to study the mode of action of his molecules. Dr. Diaz plans to begin evaluating compounds using in vivo models of traumatic brain injury (TBI) which could open a lot of future grant writing opportunities. Dr. Diaz states, “the unique environment of the CoBRE offers access to resources such as protein expression and purification to understand the effect of our compounds as well as fantastic administrative support.” He admits that leveraging the work for the company with academic research and teaching can pose challenges, but he values the fact that they can offer industrial positions to motivated UM graduates, thus helping them to understand the challenges of working in biotechnology. “Although we are not located in a hub such as Seattle or Boston, we are still able to successfully build our company to compete with bigger and well-funded small companies,” Dr. Diaz says.

When asked what lessons were learned as a CoBRE Junior Investigator, Dr. Diaz described the opportunity “as a lever to develop the research for junior investigators.” Every Junior investigator needs to find their niche of research to be productive and obtain funding. Dr. Diaz finishes by saying, “the opportunity to access scientific resources, funding, grant review workshops, and administrative support, decreased the stress and allowed me more time to think about what I’m passionate about.”

When asked about the qualities of the built and natural environment in Missoula that perhaps he and his family wouldn’t have access to elsewhere, Dr. Diaz reports that Missoula is a great place in terms of quality of life. He continues, “In contrast with larger cities, you don’t lose time stuck in traffic to commute.” Dr. Diaz is savvy and instead dedicates the time saved to family, work or hobbies. Specifically, Dr. Diaz enjoys how easy it is to go outside – weather dependent - and run to decrease stress or simply think through a specific problem. As a family, the Diaz’s appreciate downhill skiing at Snowbowl and a drink at the end of the day with friends.