The INK-ARF Pathway
The Poi Lab has focused on the cancer biology and preclinical development of anticancer agents for the treatment of head and neck cancer. Our research incorporates clinical pharmacology principles (pharmacokinetics, pharmacodynamics, drug metabolism, drug transport, drug-drug interactions) in drug development. Our lab has been studying the genetics and roles of the CDKN2A/2B genes and related pathways in human cancers. The CDKN2A/2B locus is fascinating because it codes for 3 tumor suppressors, namely P14ARF, P15 and P16.
DNA Repair Pathways in Multiple Myeloma
Using similar approach, that is integrating clinical pharmacology principles (pharmacokinetics, pharmacodynamics, drug metabolism, drug transport, drug-drug interactions), our group is also interested in understanding the roles of the DNA repair pathway genes in multiple myeloma patients and treatment response to high dose melphalan (an alkylating agent) in the setting of autologous stem cell transplant. High-dose melphalan (HDM) followed by autologous hematopoietic stem cell transplant (auto-HSCT) is currently a cornerstone treatment for multiple myeloma (MM). However, interpatient variability in melphalan pharmacokinetics (PK) and pharmacodynamics (PD) contribute to both excessive adverse effects and inadequate dosing resulting in treatment failure. The primary factors responsible for melphalan interpatient variability are largely unknown but numerous studies have suggested that variation in inter-individual DNA repair capacity may partially explain the variability. Our long-term goal is to elucidate, validate, and incorporate factors (including genetic factors) responsible for melphalan interpatient variability into a PK/PD model that physicians can use to personalize melphalan dose.