Assistant Professor, Center for Integrative Chemical Biology and Drug Discovery
Area of Interest
A central tenet of our research is the development of small molecule tools and therapeutic leads for the treatment of unmet medical needs. For example, while much progress has been made targeting primary tumor sites certain types of cancer still present disproportionately high mortality rates. Pancreatic cancer has a mortality rate of over 90%, mainly through metastasis of the primary tumor. We have discovered the effective antimetastatic agent metarrestin that reduces the prevalence of the perinucleoar compartment (PNC), a phenotypic indicator of metastatic potential. The PNC represents an alternative approach in which the complex in vivo events of malignancy are represented using a cancer-unique surrogate marker. The strategy is inspired by the century-old clinical practice, in which morphological characteristics of cancer cells and tissues are prognostic. Complex cytological features should reflect cancer cell malignancy more comprehensively than assessment of a single gene or gene product. Metarrestin has demonstrated in vivo efficacy in preventing or reducing the metastatic transformation from tumor grafts in several mouse models and substantially extends animal survival. In collaboration with Sui Huang at Northwestern and our National Institutes of Health partners (NCATS and NCI), we have advanced metarrestin into phase I human clinical trials for treatment resistant solid tumor patients. We are currently developing next generation metarrestin derivatives and advancing new PNC disruptor small molecules as complementary chemical tools and new preclinical leads. We aim to develop molecules possessing improved therapeutic indexes and selective CNS penetration or restriction. Such derivatives could lead to more potent and selective agents to serve an expanded patient population that would benefit from selective anti-metastatic agents as part of their therapeutic regimen.
Other research efforts are aimed at better understand neurotransmitter signaling. Our current efforts focus on programs for the kappa opioid, dopamine and sigma receptors. Each is a highly collaborative effort in concert with screening facilities and pharmacology experts, which has led to the identification of selective modulators for the individual receptor subtypes or signaling pathway. A related area of high interest is the identification of allosteric modulators, with our efforts on this front focused on individual dopamine receptor subtypes. Overall, the identification and characterization of selective CNS molecular tools will greatly aid the investigation into the nuanced regulation and interconnectivity of neurotransmitter signaling.
Awards and Honors
- IBM and RJ Reynolds Junior Faculty Development Award, 2021
- Training in Neurotherapeutics Discovery and Development for Academic Scientists Course, Bethesda MD (Sponsored workshop through NINDS Grant 1R25NS077582), 2016
- 9th Chapel Hill Pharmaceutical Sciences Conference 2nd Place Poster Award Winner, 2015
- University of Kansas Pharmacy Graduate Honors Symposium Invited Oral Presenter, 2009
- Stereochemistry Gordon Research Conference Exceptional Accomplishments in Organic Chemistry Award, 2008
- ACS Delaware Local Section, 2nd Place Poster Award Winner, 2004