Evgeny Krynetskiy, Ph.D., D.Sc.
Associate Professor, Department of Pharmaceutical Sciences
3307 N. Broad Street
Philadelphia, PA 19140
office Room 538A
phone (215) 707-4257
My research is directed toward elucidation of factors that define efficacy and adverse effects of drugs in patients. Therefore, the research program of my lab is focused on two interrelated areas: molecular events triggered by drug interactions with the human cells, and genetic factors that affect or modulate these interactions.
For example, one of our ongoing projects is related to anticancer drugs: we want to know how these drugs targeted against DNA eradicate cancer cells. We found that the chemical changes introduced by anticancer drugs into DNA are detected by special cellular sensors triggering a variety of intracellular processes such as cell growth arrest and programmed cell death (apoptosis). We identified these sensor proteins which avidly bind damaged DNA. In this study, we work with genetically altered human cancer cells as a model system, and use a variety of molecular and cellular methods. With better knowledge of how exactly anticancer drugs kill tumor cells, we will be able to develop more effective and less toxic anticancer regimens.
Of course, there is no such a thing as "a patient"; everybody is individual with his/her specific weight, height, appearance, as well as capacity to process and respond to drugs. Many of these characteristics are genetically inherited. That is why the second area of interest in my lab is Pharmacogenomics. The goal of this discipline is the analysis of genetic factors which define an individual's capacity for transport, metabolism, and response to drug medications.
Which ones and how many of about 22,000 human genes are involved in response to a specific drug? Obviously, to answer these questions, we first have to collect DNA samples from patients. This work is performed together with physicians from the Temple University Hospital. Our Center for Pharmacogenomics is equipped with robotic systems for DNA purification and analysis; here we perform genotyping of patients' samples. Besides, in collaboration with Fox Chase Cancer Center, we also perform genome-wide analysis using modern DNA microarray technology. By using these novel technologies, we identify the candidate genes responsible for differences in drug effects. To verify our findings, we use transgenic human cells modified with variant genes discovered in patients' DNA.
These two areas of activity in my lab are intertwined and complement each other: by learning the exact mechanisms of drug action, we are able to define candidate genes for our genetic studies, and by characterizing the genetic variations in these genes we develop diagnostic tools predictive of efficacy and toxicity of pharmacotherapy. The goal of these studies is to develop tools and therapeutic modalities of "personalized medicine" tailored for a specific genetic makeup of "the patient."